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Yale Laboratory Medicine Intranet http://info.med.yale.edu/labmed/intranet/ username = password = labmed
Manual is available online http://info.med.yale.edu/labmed/intranet/files/oncall/Manual/ http://info.med.yale.edu/labmed/intranet/files/oncall/Manual/ManualContents.txt Phone list is available online http://info.med.yale.edu/labmed/intranet/files/ On Call Primer is available online http://info.med.yale.edu/labmed/intranet/files/orientation/ Computing folder has info on how to access the Intranet/FTP, YNHH labs from home, BB database, VA VPN, Yale library, etc. http://info.med.yale.edu/labmed/intranet/files/computing/ http://info.med.yale.edu/labmed/intranet/files/computing/ComputingContents.txt BLOOD BANK: The Medical Director MUST be called when any of the following conditions are suspected or proven: Acute intravascular hemolytic transfusion reaction Septic transfusion reactions TRALI New apheresis patient referral Incompatible blood is given to any patient Death as a result of transfusion Anaphylactic reaction to blood Seizures in a blood donor Inadequate blood inventory or Red Cross supply available as backup Disagreement with members of the medical staff regarding blood ordering or transfusion reaction work-up Cardiac arrest in an apheresis patient Need to switch component blood type for a patient If the thought crosses your mind...... Blood Bank Sample Labeling Policy 1)Properly identify the patient. All patients must be identified by a stamped or hand written wristband. In clinic settings only, a label may be applied to the patient’s clothing in lieu of a wristband. 2)Blood Bank samples must be drawn in pink or lavender stopper (EDTA) tubes. 3)Samples must be labeled in the presence of the patient with the following information, using a CCSS label, addressograph label, or handwritten label: Patient’s full name Patient’s Medical Record Number (or if the MRUN is not available, patient’s DOB) Date sample was drawn All samples MUST bear the first name (or first initial) and last name of the person drawing the sample. If not present, the sample will be discarded! 4)Blood Bank samples are acceptable for crossmatch for 3 days from the date drawn, with the exception of EAS samples. 5)EAS (Express Admission Surgery) samples are tested (type and screen) when drawn. The EAS sample is acceptable for crossmatching blood for surgery occurring within the next 30 days if the patient has no antibody or history of an antibody, AND has not been transfused or pregnant in the last 3 months. The EAS sample may be used for crossmatching for 3 days post-op. Blood Components and Indications for Transfusion: Packed Red Blood Cells… “Red Cells” Collection process: phlebotomy Average volume: 250 mL Storage time to expiration: 42 days, with additive solutions Storage conditions: 1-6C Hct in bag = 52-60%, expect rise in Hct 3% per unit Infusion rate: 2-4 hr Indications: SEE AUDIT CRITERIA RBCs are used to treat patients in need of increased oxygen carrying capacity. The patients are generally anemic, and they may not have the ability to produce red blood cells as a result of impaired bone marrow or renal function. Red cell transfusions should be administered based on clinical need and not based on laboratory (CBC or other) values. Platelets Collection process: Separated from whole blood after phlebotomy - random donor platelets, RDP Plateletpheresis - single donor platelets, SDP Average volume: 50 mL (RDP); 300 mL (SDP) Storage time to expiration: 5 days Storage conditions: 20-24C (room temp) with continuous gentle agitation Expected CBC increment in a non-acute hemorrhage: 5,000/L (RDP); 30,000 L (SDP) Random donor units are pooled (Yale = 4 unit pools, VA = 5 unit pools), once pooled platelets must be transfused in 4 hours or less Infusion rate: variable Indications: SEE AUDIT CRITERIA Platelets are used to treat patients who are bleeding as a result of thrombocytopenia. In the surgical or trauma setting, platelet counts below 50,000/L will be treated if the patient is bleeding. In the oncology setting, platelet counts below 10,000 to 20,000 L will be treated with platelet transfusions. In general, one does not transfuse platelets at a specific “trigger” count, but one will follow decreasing platelet count trends and administer prophylactic platelets in at-risk patients. Fresh Frozen Plasma “FFP” Collection process: Separated from whole blood after phlebotomy (frozen w/in 8 hrs.) Average volume: 220 mL Storage time to expiration: 1 year Storage conditions: frozen at temperatures below (-18C) Expected increment in a non-acute hemorrhage: A typical dose of FFP is 2-4 units. One can expect an increase in all coagulation factors by 10-20% with this dose. Must be thawed then transfused within 24hrs, Provides all coagulation factors, dose of 10-20 ml/kg expect 20% increase in factors Infusion rate: 4-10 ml/min Indications: SEE AUDIT CRITERIA FFP is used to treat patients who are bleeding as a result of global coagulation factor deficiencies. In the surgical or trauma setting, coagulation factors may be reduced due to dilution of the factors during fluid resuscitation and/or consumption due to bleeding or DIC. In the medical setting, conditions such as liver disease and vitamin K deficiency can result in a decreased production of coagulation factor proteins. For management of elevated INR, see American College of Chest Physicians (ACCP) guideline especially Table 6 [Ansell J, Hirsh J, Poller L, Bussey H, Jacobson A, Hylek E. The pharmacology and management of the vitamin K antagonists: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest. 2004 Sep;126(3 Suppl):204S-233S. Erratum in: Chest. 2005 Jan;127(1):415-6. dosage error in text.] Pdf version is available on the Intranet http://info.med.yale.edu/labmed/intranet/files/oncall/Manual/ Cryoprecipitate Collection process: Separated from whole blood after phlebotomy, prepared from FFP thawed at 1-6 C, supernantant plasma is removed and remaining precipitated proteins and small amount of plasma remain as “cryo”. Average volume: ~15cc each unit Storage time to expiration: 1 year Storage conditions: frozen at temperatures below (-18C), thawed at 1-6 C, then kept at 20-24C, should be transfused within 6 hr of thawing and 4 hr of pooling. Infusion rate: 5-10 ml/min Indications: hypofibrinogenemia, Factor XIII deficiency, von Willebrand’s disease, hemophilia A, uremic bleeding Cryo is rich in VWF, Factors VIII and XIII, fibrinogen, and fibronectin, expect fibrinogen rise to be 5mg/dl per unit of cryo. Hemostatic level of fibrinogen >100 Calculation for hypofibrinogenemia: Adult: typical dose 10 units of cryo plasma volume: 40 ml/kg (adult), Child: 80ml/Kg (TB volume x (1-hct)) Formula = Desired fibrinogen (200) – Actual Fibrinogen X Plasma volume in dL Mg/bag (200) Concerns During Transfusion of Blood Products Once any blood product is “spiked” or “opened,” the transfusion should be finished within 4 hours. This minimizes any potential bacterial growth due to contamination at the time of the “spike.” (It is also a mandate by the government and standard in the United States.) See Goodnough LT. Risks of blood transfusion. Anesthesiol Clin North America. 2005 Jun;23(2):241-52. Pdf version is available on the Intranet http://info.med.yale.edu/labmed/intranet/files/oncall/Manual/ Transfusion Reactions: See Transfusion reaction section Transfusion Transmitted Diseases “TTD” Transfusion 1. Needle: 18 gauge or larger; if veins too small, use 23 gauge or larger, but slower flow rate (watch out for hemolysis) 2. Filter: standard 170 micro in line filters to trap cellular debris and coagulated proteins 3. Blood warmer: <42C 4. No mix with iv medication, except: normal saline, 5% albumin, plasma protein fraction. Jehovah’s witnesses: we do not have blood substitutes. The Associated Jehovah’s Witnesses for Reform on Blood http://www.ajwrb.org/ does not represent mainstream Witness views. However, they do refer to the general Witness policy that red cells, white cells, plasma, and platelets are NOT acceptable, but fractions are a personal choice. See commentary on June 2004 WatchTower figure http://www.ajwrb.org/6-15-04.shtml Use of Leukocyte Reduced Blood Products A leukocyte reduced blood component contains < 5 x 106 donor leukocytes per final product. Current blood filters and apheresis devices are capable of reducing residual WBC content to well below 1 x 106. Total of 109 of WBC in blood components. Prestorage leukoreduction is the preferred method as it prevents cytokine accumulation and microparticle formation and is standard practice at Yale for all red blood cell and platelet inventory. Reduce the risk of febrile nonhemolytic transfusion reactions, HLA alloimmunization, CMV transmission. Use of CMV-safe Blood Products Cellular blood components have a reduced risk of transmitting CMV Infection (“CMV safe”) if: a)They are tested and found to be sero-negative for CMV antibody or b)They are pre-storage leukoreduced, 99.9% or 3 log reduction These two methods are considered to provide equivalent reduction of risk of CMV transmission. Bedside filtration with a leukoreduction filter is not considered adequate to reduce the risk of CMV transmission. Use of washed RBC Wash with normal saline to remove 99% of plasma proteins, electrolytes, and antibodies. Used to prevent recurrent allergic reaction, anaphylactic transfusion reaction, hyperkalemia in pediatric patients, and also for post transfusion purpura. Takes 20-30 min extra time. Thawing and Deglycerolization Used when rare Ag negative RBC are used. Takes about 20-40 min, and repeated freeze-thaw may result in loss of volume. Incompatible blood administration When incompatible blood has to be given (in emergent cases or in cases of autoimmune hemolytic anemia or an alloantibody to a high incidence RBC antigen or no cross match compatible blood available), the resident should notify the clinician about the situation and let them decide to proceed with the transfusion or not , and communicate with the blood bank attending when time permits. Recommend a test dose for administration if has to be released, 15 cc in 10 min and check patient’s vital signs and status closely. Release of Uncrossmatched Blood 4-6 units of O negative red cells, tagged for emergency release, are stored in each of two Blood Bank refrigerators, one located in the ED Trauma Room (6 units) and one in the OR (4units). Also, uncrossmatched blood can be obtained directly from the Blood Bank; this can be either O negative or, if time permits and a valid current patient sample is available, type specific. The transfusing physician is responsible for signing the release form for use of uncrossmatched blood and having this form returned to the Blood Bank as soon as possible. Massive transfusion protocol can be initiated when necessary by a clinical attending, initial box in the Blood bank includes; 10 O neg RBC, 2 units of thawed FFP, 1 SDP. Uncrossmatched blood will be cross-matched retrospectively and it is the resident’s responsibility to inform clinicians if the blood was incompatible and warn about signs of hemolysis. Use of Irradiated Blood Products Cellular blood components are exposed to gamma radiation to prevent the proliferation of T lymphocytes which can lead to transfusion asssociated graft vs host disease (GVHD), especially in immunosuppressed or neutropenic patients or patients with hematologic malignancies and dysfunctional immune systems. When a patient is at risk for GVHD, all cellular components, RBCs, platelets, and granulocytes, must be irradiated. In addition, components from a blood relative (direct donation) or HLA-matched donor must be irradiated (except hematopoietic progenitor cells). Similarity in HLA may result in survival of transfused lymphoctyes and thus lead to GVHD. Irradiation of with a minimum dose of 2500 cGy is recommended by AABB and FDA standards. It requires a few minutes at Yale, but may take several hours for VA, due to transportation time. After irradiation, expiration time becomes 28 days, and with increased K leakage, (wash for Exchange transfusions for infants). A good review of TA-GVHD is Schroeder ML. Transfusion-associated graft-versus-host disease. Br J Haematol. 2002 May;117(2):275-87. Pdf version is available on the Intranet http://info.med.yale.edu/labmed/intranet/files/oncall/Manual/ Check the Resident Blood Bank Manual to see the current YNHH SOP for irradiation. From the 2005-2006 version on the Intranet http://info.med.yale.edu/labmed/intranet/files/oncall/BloodBankManual/ Indications for irradiation of cellular blood components include: products A. All directed donations of cellular components B. All cellular components for use in the Newborn Special Care Unit C. All cellular components for all children under four months of age D. All cellular components for infants undergoing extra-corporial membrane oxygenation (ECMO) E. All single-donor platelets or granulocytes DIAGNOSIS / DISEASE STATE A. Congenital Immune deficiency B. Acute leukemia C. Lymphoma D. Neuroblastoma, rhabdomyosarcoma, glioblastoma multiforme E. Patients who have received or are about to receive peripheral blood stem cell transplants or bone marrow transplants (allogeneic or autologous) F. Donations from blood relatives G. Any patient receiving high dose immunosuppressive chemotherapy such as Cytoxan and Fludarabine H. Solid organ transplants. For details, refer to SOP BB 6.14, Solid Organ Transplants I. Myelodysplastic Syndrome Other requests will be discussed first with a Blood Bank physician. This includes requests for patients with aplastic anemia, but only if receiving or within one month of having completed ATG. Irradiated products are suitable for any patient, even if they do not require it. AIDS is not an indication for irradiation. See Schroeder ML review about no cases of TA-GVHD in AIDS. Transfusion Reaction Workup All adverse reactions associated with blood transfusion must be reported to the Blood Bank by the clinical service performing the transfusion. Responsibilities of the Clinical Service administering the transfusion: Stop the transfusion immediately. Keep IV open with a suitable solution such as 0.9% NaCl. Report at once to the responsible physician and to the Blood Bank. Send freshly drawn and properly labeled lavender top tube, component bag, all attached IV lines and fluids, and transfusion reaction form (F1934) (can be ordered in CCSS, order/blood bank/transfusion reaction evolution, the only copy should be printed out automatically when the order is finished) to the Blood Bank at once. (see example) One exception to the above is a MILD allergic reaction presenting with a localized rash (hives) ONLY. In this instance, the patient can be treated with an antihistamine (Benadryl) and the reminder of the unit can be infused if the symptoms disappear and no fever, chills, or cardiorespiratory signs or symptoms occur. Blood Bank Technologist’s Work-up of Transfusion Reactions: Perform clerical check to assure that the blood was issued/ transfused to the correct patient. Examine post-transfusion specimen for hemolysis. Perform ABO/ Rh, DAT testing on post-transfusion specimen. Fill out the front of the “Transfusion Reaction Workup” form (Form 1933) Resident’s Work-up of Transfusion Reactions: Initial call check list: Is the patient stable? How bad is the reaction? If there are signs of: Hemolysis Very high temp SOB Increased O2 requirement Bronchospasm Hypotension DIC Call the attending right away! Why is the patient in the hospital? Is the patient bleeding, how and from where? How many units were transfused, when started, when stopped? How much of the unit was transfused? Need more transfusion right away? Pre and post transfusion vitals Pre and post transfusion labs Transfusion reaction work-up check list Make sure the form of transfusion reaction evaluation is sent by the physician Finish the work-up form Obtain the yellow compatibility tag and return to chart Finish the audit form Fill out and sign the sticky Ask the attending to sign all the forms Put the sticky OR a note into the chart ASAP. A notation must be made on the patient’s chart regarding the outcome of the work-up within 24 hours. For this purpose, the resident should contact the Blood Bank Medical Director by phone to review the reaction if it occurs on a weekend. The resident will make an initial diagnosis of the type of reaction. The resident is also responsible for determining if subsequent transfusions may be given once the workup is complete. If the resident has difficulty making a definitive diagnosis of a transfusion reaction, the Blood Bank Fellow on call or the attending on call MUST be consulted. TYPES OF REACTIONS: Acute hemolytic transfusion reaction: The first job is to rule out an acute hemolytic transfusion reaction based on Blood Bank laboratory tests (negative DAT and the absence of hemolysis). The sine qua non of an acute intravascular hemolytic reaction is red plasma and red urine- hemoglobinemia and hemoglobinuria. Both must be present. A plasma hemolysis usually looks pink when the level is > 20 mg/dL. If hemolysis is suspected, additional tests can be ordered (plasma and urine hemoglobin, LDH, indirect and direct bilirubin, and haptoglobin). Management of an acute hemolytic transfusion reaction includes monitoring the urine output to ensure that it is at least 100 mL/hr for 18-24 hours. Treatment with IV normal saline should be initiated. Remember, hydration should be performed judiciously in patients with cardiac failure or renal failure. Diuretics are helpful to improve renal perfusion. If no diuretic response occurs after several hours, acute tubular necrosis should be evaluated. Avoid diuretics in patients with compromised renal function. Febrile non-hemolytic transfusion reactions (FNHTR) are a temperature rise greater than 1C, possibly accompanied by chills, that occurs during or up to 2 hours after a transfusion and is not attributable to another cause. FNHTR are caused by antibodies to leukocyte antigens or cytokine infusion. It is a diagnosis of exclusion. Determine if the patient has had recent fevers by reviewing vital signs in the hospital chart. If fevers occurred prior to reaction, determine what etiology is most likely and document the frequency of occurrence. If symptoms (e.g., shaking chills) accompanied the suspected transfusion reaction, did these symptoms also occur prior to transfusion? The treatment of a febrile non-hemolytic reaction includes an antipyretic such as acetaminophen. Recommend future premedication with acetaminophen if suspect a febrile non-hemolytic reaction. Review all cases with the Blood Bank Medical Director. Allergic Reactions are associated with symptoms vary from urticaria, hives, itching to anaphylaxis and may occur up to2-3 hours after a transfusion. They are likely caused by antibodies to plasma proteins or rarely antibodies to IgA. Document the extent of rash and any additional symptoms. Determine if there was difficulty breathing and if it was associated with throat swelling (laryngeal edema). A mild localized urticarial-pruritic rash should be treated with Benadryl, 25-50 mg (adult dose). IF THIS IS THE ONLY SIGN AND SYMPTOM and if it goes away after treatment, the same unit of blood can be given safely. For patients with frequent allergic reactions it should be recommended that they are pre-treated with an antihistamine (Benadryl) for subsequent transfusions. If a patient who has never received a blood product has an anaphylactoid allergic reaction, consider testing for IgA deficiency. The treatment for anaphylaxis includes stopping the transfusion and administering epinephrine. Oxygen therapy and possibly corticosteroids are also helpful. Intubation and pressors may be needed if shock occurs. Circulatory overload is manifested by pulmonary edema associated with blood transfusion. This typically occurs in patients with a history of congestive heart failure or the elderly. Diuresis or phlebotomy should be considered. Transfusion-associated sepsis is seen when transfused blood products are contaminated with bacteria. Usually manifests as fever, chills, rigors, shock. If septic transfusion reaction is suspected, specimens from both the patient and the transfused unit should be sent for gram stain and culture. Transfusion-related acute lung injury (TRALI) is caused by donor antibodies against recipient HLA or leukocyte antigens which lead to leukoagglutination and occlusion of the microvasculature of the lung. The patients present with dyspnea, fever, chills, respiratory failure and a cxr that shows pulmonary edema. Treatment is supportive and the donor units should be quarantined until etiology established. Hypotensive reactions appear to involve the generation of kallikrein by some types of biomaterials (especially bedside filters) leading to bradykinin production which in turn can lead to hypotension. Patients on ACE inhibitors are at greater risk for this complication. Massive transfusions can cause citrate toxicity, generally manifested as symptoms of hypocalcemia. Other reactions: Hypokalemia Hyperkalemia Hypothermia Serology Work-ups/New Antibody: The blood bank will call when a new antibody is found on an antibody screen and panel work-up. It is the resident’s responsibility to find out the medical and transfusion history of the patient and talk with the clinician regarding the findings. A notation should be made in the chart. An example of a note follows: Blood Bank Resident Note The antibody screen was positive on __________. Anti- _______ was identified in the serum. The DAT was _______. The auto-control was _______. The patient was last transfused ________. At that time the antibody screen was negative, and compatible red blood cells were given. The detection of anti-________ is a new finding for this patient. Anti- _______ antibodies can cause clinically significant hemolytic transfusion reactions; therefore, all future transfusions should be ________-negative red blood cells. The patient can be monitored for signs of hemolysis by checking the Hematocrit, LDH, Bilirubin, BUN and Creatinine, and urinalysis. Consult the following paper on the clinical significance of antibodies. Thrombocytopenia/Platelet Refractoriness Thrombocytopenia Check list: Is the patient on anti-platelet medication? Is the patient post-op? Is the patient uremic? Is there Active bleeding? How much? What was the last platelet count? Do you have post-transfusion platelet counts? Is the patient febrile? Does the patient have a big spleen? 1) A patient who is refractory to platelet transfusions can be evaluated by determining if there is a sufficient increase in platelet count, sampled between ten minutes and one hour after transfusion. If there is not a sufficient response to platelet transfusion immediately, and if the patient does not have sepsis, splenomegaly, DIC, massive bleeding, drugs causing thrombocytopenia, fever, the refractory state may be due to immune clearance (HLA or platelet antibody) of the transfused platelets. Crossmatched or HLA matched platelets may be helpful for patients who have alloimmune platelet refractoriness. 2) A sufficient increase in platelets after transfusion can be determined by calculating the corrected count increment (CCI) for a sample drawn 10 minutes to 1 hour after platelet transfusion. An acceptable CCI = >7.5x109/L for a sample drawn 10 minutes to 1 hour after infusion. For a sample drawn 18 to 24 hours after infusion, >4. 5x109/L is considered acceptable. CCI = (platelet countpost/L - platelet countpre/L) x Body Surf. Area (M 2) Number of platelets transfused ( in multiples of 1011/L) Note: Single donor platelets ~ 3.0x1011 Random donor platelets ~ 0.6x1011 x number of units in pool (~ 4) 3) A CCI less than 4,000-5,000/L is a decreased response to platelet transfusion. This decreased response in the early time period after platelet transfusion is characteristic of immune clearance in a patient who is refractory to transfusion. A low CCI value calculated for two different platelet transfusions warrants the Blood Bank sending a sample (one EDTA purple tube) to the Red Cross for platelet antibody screen. If positive, a crossmatch compatible single donor platelets should be used for the patient. Even HLA compatible or crossmatch compatible platelets may not produce a good CCI in a refractory patient. “Platelet Drip” Infusions Continuous platelet infusions, “platelet drips,” have not been formally studied to validate their effectiveness as an alternative to the standard method of infusing platelets. There are times when a patient receives multiple platelet transfusions, and the benefit or rationale for the transfusions is questionable. If additional platelet transfusions are requested, the resident may recommend a platelet drip as a method of conserving platelets. Conservation of platelets may be needed to ensure an adequate supply of platelets for potential patients who would benefit from platelet transfusions. The maximum order for a platelet drip is 3 units given over four hours. Consult with the Medical Director, or his designee. Coagulation Factor Concentrates 1) Factor VIII concentrates are now used instead of cryoprecipitate for patients with Hemophilia because Factor VIII concentrates are processed or manufactured to reduce or eliminate the risk of TTD. The dose of Factor VIII depends on whether the therapy is prophylactic or, if for bleeding, the nature and severity of bleeding. The dose is calculated based on the patient’s measured factor VIII level. (Cost ~$1/unit) Dosage required (IU) = PV x [desired level (%) - initial level (%)] 100 where plasma volume (PV in mL) = 40 mL/kg x body weight (kg) The half-life of Factor VIII is 12 to 18 hours, although the half-life of the initial dose is about 4 hours because of extravascular equilibration. If the patient has had major surgery, the level of Factor VIII should be maintained above 40-50 units/dL for at least 10 days. Consult the package insert(s) for details. Factor VIII concentrate products that contain biologically active vWF (Humate-P and Alphanate) are useful for treatment of severe von Willebrand Disease. The activity of vWF in these products is measured as Ristocetin Cofactor (vWF:RCof), and expressed in IU. 1st generation recombinant : Kogenate, Bioclate, Helixate, and Recombinate 2nd generation recombinant: B-domain recombinant Factor VIII Monoclonal Ab purified Factor VIII: Monarc-M, Hemophil M, Monoclate P Other plasma derived Factor VIII concentrates: Humate P, Koate DVI, Alphanate, and Profilate: used for vWD 2) Porcine Factor VIII (Hyate:C) is indicated for the treatment of Hemophilia A patients with inhibitors to human Factor VIII (high but <50 human Bu, but very low porcine Bu, <10-20 BU) and for non-hemophiliac patients with spontaneously acquired inhibitors to Factor VIII. Very hard to get, have to contact the company, only for life threatening or limb losing bleedings. 3) Factor IX concentrates are used for Hemophilia B (congenital Factor IX deficiency or Christmas disease). Dosage required (IU) = PV x [desired level (%) - initial level (%)] 100 where plasma volume (PV in mL) = 40 mL/kg x body weight (kg) The half-life ranges from 18 to 32 hours, although the half-life of the initial dose is about 4 hours because of extravascular distribution. Therefore, a patient’s first dose is usually double the amount of Factor IX calculated. 4) Factor VIIa (NovoSeven) is a recombinant product which is indicated for the treatment of bleeding episodes in Hemophilia A or B patients with inhibitors to Factor VIII or IX, or other factor deficiency. (Cost = $1000/mg). Typical starting dose is 75 (20-90) ug/kg bolus, q 2 hours, not recommend continuous iv infusion, as less effective and more thrombosis risks. For a patient with a factor deficiency, watch out for thrombosis. Check the indication and patient status at each dose, try to prevent the wasting of the products. 5)Prothrombin complex concentrates (PCC): Konyne 80, Bebulin, Profilnine SD and PropexT plasma derived concentrates containing: Factor II, VII, IX, and X. 6)Anti-inhibitor Coagulant complexes (activated prothrombin complex concentrates or APCCs): Autoplex T and Feiba VH: heat-treated, plasma-derived anti-inhibitor concentrates that have a high content of factors VIIa, IXa and Xa. Used to treat bleeding in patients with FVIII inhibitors. Thrombosis risk. Treatment for vWD: Humate P (lyophilized, pasteurized, concentrate of human plasma derived FVIII and vWF; Koate DVI (Double Viral Inactivated), FVIII concentrates purified from pooled human plasma which is solvent detergent treated; Alphanate, extracted from human plasma. Treatment for Hemophilia B: recombinant FIX (rFIX; BeneFix) and two plasma-derived FIX products, Alphanine and Mononine. Package inserts for NovoSeven, Advate, Helixate, FEIBA, Humate-P, and Benefix are available online (Google search); latest versions as of Spring 2006 are on the Intranet http://www.us.novoseven.com/content/us_vers/downloads/0804NovoSevenPI.pdf http://www.advate.com/images/pdf/prescribing_info_english.pdf http://www.zlbbehring.com/ZLBB/binary/HelixateFSPI.pdf http://www.hemophiliagalaxy.com/pdfs/therapies/Feiba.pdf http://www.humatep.com/pdf/HumateP_PI.pdf http://www.hemophiliavillage.com/benefix_product.asp Rh Immune Globulin If an Rh negative patient (including a mother) is exposed to Rh positive red cells, the development of antibody to the D antigen can be prevented by administering Rh Immune Globulin (RhIG). Exposure to Rh positive red cells can occur through transfusion of platelets or granulocytes, or through pregnancy. A patient who is deliberately given units of Rh positive red cells (as in an emergency), is not a candidate for RhIG by virtue of the volume involved. WinRho is an IV preparation, obtainable in various sizes from the Pharmacy; RhoGam is for IM injection only and is stocked by the Blood Bank. Rh immunoglobulin should be given within 72 hours of exposure to D positive cells. It is considered malpractice to not treat an Rh negative mother (who has not previously formed anti-D) with RhIG at clinically appropriate times during pregnancy and at delivery of an Rh positive (D) baby. A patient’s Blood Bank serologies will be affected after receiving any RhIG: the direct antiglobulin test (DAT) might be positive because of the presence of the RhIG attached to D positive red cells; the antibody screen/panel will be positive because of the circulating RhIG. A single dose of RhIG (300 g) prevents sensitization to the D antigen in < 30 mL of whole blood (or 15 mL of red cells). If the volume of exposure is greater than 30 mL of whole blood (15 mL red cells), additional RhIG needs to be administered. The total dose of RhIG (300 g) is determined by dividing the estimated volume of the whole blood exposure by 30 (the volume of whole blood neutralized by one dose) or the estimated volume of the red cell exposure by 15 (the volume of red cells neutralized by one dose). Consult the PDR or RhIG package insert for specific dosing requirements. 1.Transfusion of Rh positive platelets or granulocytes: RhIG should be given to Rh negative patients who receive Rh positive platelets or granulocytes. The physician must be notified of this in advance so that he/she can reconsider the need to transfuse any blood products. Although Rh immunoglobulin is a relatively safe medication, the physician should have the opportunity to consider the implications of the transfusion in advance. IM preparations (RhoGam) can be problematic if a large dose is needed, IM administration is contraindicated, or if the patient has cardiac disease (can interfere with the laboratory tests for MI), and the patient is thrombocytopenia to begin with. For these reasons, WinRho might be recommended because it can be administered IM or IV. It is available in smaller doses, such as 120 g. Larger doses can be administered, at a rate up to 600 g Q 8 hours IV, until the total dose is given. If you recommend WinRho, the resident should be informed that it is non-formulary and they will not be able to order it through the CCSS system. The resident should call the pharmacist to facilitate the order. A single random donor unit of platelets, even when prepared properly, can have as much as 0.5 mL of red cells. (This is the worst case and the unit would be bright red. Most units have far fewer red cells, but always assume the worst case amount.) Thus, in a 4 unit pool, there possibly might be as much as 2 mL of red cells. Since one RhIG dose (300 g) is sufficient to neutralize 15 mL of D positive red cells, the patient might receive 7 1/2 pools of platelets (4 units each), representing a total of 30 units of single random donor platelets. The physician should be advised to administer another dose when more platelets are to be transfused. Consult with the Medical Director or designee when RhIG is administered for treatment due to receipt of Rh positive platelets. A unit of single donor apheresis platelets (“Platelets, Pheresis”), might contain as much as 5 mL red cells, so 1 dose of RhIG would only cover 3 units of this product. 2.Maternal exposures: An Rh negative mother of a D positive infant must receive RhIG within 72 hours of delivery. A full dose of 300g is usually prescribed. Testing for fetal-maternal hemorrhage: The rosette test is used to screen Rh negative women (should be done for all Rh negative woman post delivery) for a maternal-fetal hemorrhage (MFH) larger than 10 mL of Rh positive cells. A Kleihauer-Betke acid elution test is done if the rosette test is positive. It quantifies the extent of MFH by estimating the percentage of fetal cells present in the mother’s red cell volume. The result is reported either as % or as No. per 105. See Hematology section for calculation of RhIg dose. Massive Transfusion This is defined as the infusion of blood and components in amounts approaching or exceeding one blood volume (about 12 units) over a 24 hour period. Management of this situation includes assessing the available blood inventory to support the patient. Determine if it is necessary to switch the patient from type-specific to type-compatible blood products, especially for Rh negative patients. It is also important that the resident plays an active role in screening for DIC and to expedite Hematology Lab results. Suggest that the PT, PTT and fibrinogen (always done with a PT, PTT even it may not be reported) be checked if this has not already been done and make the hematology lab aware that the results are needed promptly. Make sure the clinical team considers the need for platelets, FFP and cryo as well as RBC’s. Communication between the Trauma/ Anesthesiology physicians and the Blood Bank is critical. All of these decisions MUST be made in conjunction with the Blood Bank staff and the Medical Director. DO NOT WORK in a VACUUM. Apheresis: Therapeutic and Donor The resident’s role in apheresis includes medical evaluation of the patient and need for apheresis, obtaining informed consent, and supporting the nursing staff during apheresis Indications for Therapeutic Apheresis 1) Emergency: There are three common indications for emergency apheresis: Acute chest syndrome due to sickle cell disease TTP Blastic Hyperleukocytosis 2) Other indications: Sickle cell syndrome Cryoglobulinemia Neurologic disorders: Myasthenia Gravis Gullain-Barre Syndrome Other neuropathies may respond, including chronic inflammatory demyelinating polyneuropathy and stiff-man syndrome. The Journal of Clinical Apheresis Volume 15 Issue 1-2, 2000 (1-159) Special Issue: Clinical Applications of Therapeutic Apheresis provides a good overview of therapeutic apheresis. Pdf versions including indication categories are available on the Intranet http://info.med.yale.edu/labmed/intranet/files/oncall/Manual/ Apheresis Responsibilities: (In conjunction with the Medical Director and the nursing staff): a) Before the procedure: Confirm the indication for the requested procedure. Assess the vascular access to determine if a Quinton central line or internal jugular catheter is needed. The Quinton line needed is a stiff-walled double- lumen apheresis/dialysis catheter, placed in the internal jugular or subclavian vessel. Usually the size is 11 french for adults and 7-10 french for kids Obtain height, weight and vital signs of the patient Evaluate the risk of complications. Determine the replacement fluids to be used (5% albumin/ NaCl for all but TTP patients). Evaluate medications: Patients using ACE inhibitors may experience a hypotensive reaction, particularly if albumin replacement is used in the apheresis procedure. ACE inhibitors should be stopped immediately if apheresis is started and another antihypertensive substituted. Obtain all pertinent laboratory studies. Obtain consent from the patient after explaining the possible side effects and informing him/ her of the risks of any infused blood products. If the procedure is emergent, see the Medical Director. a) During the procedure: Monitor for hypovolemia. It should not occur with continuous flow devices, but the volumes infused and returned must still be monitored closely in patients with cardiac disease or the elderly. Monitor for hypocalcemia- the citrate in the ACD-A anticoagulant will lower the patient’s ionized calcium level. FFP, hypomagnesemia, hyperventilation and hypothermia will exacerbate this citrate-induced drop in calcium. The symptoms of hypocalcemia include perioral paresthesia, tingling and numbness in the limbs, Chvostek and Trousseau signs. Apheresis General Information Stem Cell Collection 1) Peripheral Blood Stem Cells are collected for hematopoietic rescue of a patient following myeloablative chemotherapy or radiation therapy. Hematopoietic stem cells are mobilized into the peripheral blood following administration of chemotherapy and/or hematopoietic growth factors and are collected by apheresis. Both autologous and related allogeneic donors are collected at YNHH. 2) The resident’s role in the collection of peripheral blood stem cells from an autologous or allogeneic donor is similar to that for other apheresis procedures (see the preceding section). In addition, the resident should be available to expedite the patient’s and the product’s (from previous collections, if available) CD34+ counts from the Flow Cytometry Laboratory and to have the results available for discussion at Blood Bank rounds. At the time of collection, the resident is expected to consult with the attending physician to complete the PBSC Pheresis Product Worksheet, which gives processing instructions to the Blood Bank/Stem Cell Laboratory personnel as to whether the final product is to be split, frozen, and/or CD34+ selected. Plasma Exchange 1) TTP: Plasmapheresis is an extremely important and effective treatment for this disorder. Replacement fluids can include either cryopoor plasma, fresh frozen plasma, or solvent-detergent plasma. The therapeutic benefit may relate to the removal of high molecular weight monomers of von Willebrand factor. Treatment of TTP is a medical emergency. 2) Neurologic disorders: Myasthenia Gravis--Plasmapheresis is used to treat acute exacerbations. A general treatment schedule is 5 or 6 procedures over 1-2 weeks. Gullain-Barre--Early treatment is beneficial. 200 mL/kg are exchanged over 7 to 14 days. Other neuropathies may respond, including chronic inflammatory demyelinating polyneuropathy and stiff-man syndrome. Albumin generally is used as replacement fluid for these conditions. Cryoglobulinemia: Apheresis is useful to treat acute exacerbations caused by elevations of cryoglobulins which cause vasculitis, vascular occlusion, skin ulceration, nerve damage and coagulation abnormalities Cytapheresis Erythrocytapheresis 1) Sickle Cell Syndrome: A full exchange transfusion can be done, called erythrocytapheresis. This method exchanges approximately 6 units of rbc’s and is a more aggressive treatment then a partial exchange transfusion in which 2 units of blood are manually drawn and 2 units of rbc’s infused. When erythrocytapheresis is needed, the Blood Bank must be notified to prepare the units of red cells and to perform a sickle test on these units. Donated sickle trait blood must not be used because it could cause sickling within the apheresis machine. A HgbS level usually is done to determine the amount of blood that needs to be infused to reach the target of <30% hemoglobin S. A sickle column may be necessary because estimating the starting sickle cell level in the patient can result in over transfusion and unnecessary exposure to the risks of blood products. 2) For erythrocytapheresis on the COBE machine, the patient’s height, weight, hematocrit, and % hemoglobin S are needed. The requesting physician must indicate the desired post procedure hematocrit and % hemoglobin S. The Blood Bank must have a type and crossmatch and transfusion history, especially if done at another facility. 3) Emergency apheresis is not always necessary, even for a pain crisis. The procedure can be scheduled with the Apheresis Unit and Blood Bank. Sometimes only a manual exchange of two units is needed. Leukapheresis Emergency leukapheresis lowers the WBC count, although temporarily, in patients with extreme leukocytosis (blasts over 100,000/uL) due to acute myelogenous leukemia. Such high counts might cause hyperviscosity syndrome. Thrombocytapheresis Maternal platelets often are used to treat NAIT. Similar to HDN, NAIT results when the mother’s antibody to the infant’s platelets crosses the placenta, but unlike HDN, it often affects the first-born. The maternal plasma must be removed and the platelets resuspended in saline at a reduced volume. Allogeneic platelets can be used, if necessary, but they must lack the antigen being attacked by the maternal antibody and the plasma must be compatible with the infant’s red cells. All products must be irradiated and be CMV negative or leukocyte-reduced Granulocyte Collection 1) Neutropenic (generally < 500/uL) children or adults who have sepsis and who are unresponsive to IV antibiotics might benefit from granulocytes donated by a normal individual. 2) The donor is stimulated with G-CSF (5-10 ug/kg) and steroids (8 mg dexamethasone) PO 12-24 H before undergoing apheresis to harvest the granulocytes. A concentrate from a stimulated donor contains 4-8 x 1010 granulocytes, along with many of the other leukocytes and as much as 20-50 mL of red cells. A standard blood filter must be used (never a leukocyte reduction filter) and the product should be irradiated to prevent GVHD. 3) The granulocytes should be administered as soon as possible after apheresis because of well documented deterioration of granulocyte function (within 24 hours). Once transfusion therapy is initiated, support should continue for several days until infection is cured, defervescence occurs, the absolute granulocyte count returns to at least 500/mL, or the Medical Director and/or attending decide to halt the therapy. 4) All females of child bearing potential must have a negative pregnancy test prior to receiving G-CSF. Hematology Critical Value Reporting The policy per Dr. Rinder is that the Heme technologist tries first to have the clinic answering service page the on-call physician to the Heme lab. If there is no response after 30 minutes, critical value for CBC, Coag, etc. are referred to the on call resident for follow-up attempt to notify a covering physician. Kleihauer- Betke test: A K-B should be used primarily for determining RhIg dosing in cases of exposure to fetal blood in a Rh negative mother. In these cases, a rosette test may be sufficient if at least one dose of RhIg will be given; a K-B is only needed if the rosette is positive to determine if additional RhIg is needed. The K-B should not be used as a primary indicator of fetomaternal hemorrhage; fetal assessment by clinical monitoring and ultrasound are more important. This test is ordered to quantitatively assess the volume of fetal RBCs that are present in maternal blood. It is basically an acid elution process that washes out the HbA (leaving pale RBCs) while HbF remains resistant. A slide is examined and percentage of fetal red blood cells is reported. Rhogam is then dosed based on the percentage. The clinicians may ask you to help calculate a dose of Rhogam (RhIg) based on the K-B result: First, Calculate the maternal blood volume: 70 ml/kg x mother’s weight or use the volume of 5000 mL (assumes an average adult weight of 70 kg) Calculate the volume of fetal blood to which the mother was exposed: If K-B is 1.3% and mother’s weight is 70 kg ( 1.3 / 100 ) x 70 ml/kg x 70 kg = 63.7 mL of fetal whole blood in maternal circulation This is an imprecise measure, so it is standard practice to over estimate the amount of RhIG to be administered to ensure coverage of the exposure. The calculated dose is rounded to the nearest full dose and an additional dose is added to ensure that Rh sensitization does not occur. The standard dose of RhIG (300g) covers an exposure of 15 mL of D positive fetal red cells (30 mL whole blood). The formula to calculate the RhIG dose to be given depends on whether the exposure is quantitated as a volume of whole blood or red cells. Usually, whole blood volume is used in the calculations. e.g.: For this 63.7 mL fetal bleed, 63.7/30 = 2.1 the mother should get a total of 3 doses (3 300 g vials) ( 2.1 rounded* to 2 doses; add 1 dose = 3 doses total ) For an 80 mL fetal bleed, 80/30 = 2.7 thus, 4 doses are needed. ( 2.7 rounded** to 3 doses; add 1 dose = 4 doses total ) If red cell volume is desired for any reason, multiply the maternal blood volume by her hematocrit/100. Then, use 15 mL as the fetal red cells volume that is neutralized by the 300 g dose of RhIG. Rounding Rules: Always add 1 vial (dose) to the “rounded” number of vials (doses). *a. If decimal is 0.1 - 0.4, stop (round down); then add 1 **b. If decimal is 0.5 - 0.9, add 1 (round up); then add 1 STAT Hemoglobin S: The routine method for quantitation of HbS is by HPLC in special hematology. This is run during the day: Monday, Wednesday, and Friday. HbS measurements are sometimes needed on an emergent basis, usually when there is a question of whether to do an exchange transfusion; if the patient has not been recently transfused or exchanged recently, then %S should be at baseline and quantitation is unlikely to be helpful. There is really no other good reason to order a STAT HbS level. Many times it is ordered STAT by mistake and the clinician can wait for the routine HPLC method. There used to be a column HbS method which the manufacturer stopped supporting so is not run anymore. Orders for this should be directed to HPLC instead. Review of Peripheral smears: Technologists may call to tell you they have an abnormal finding in a smear. If you are still in house, you should go and look at the smear. You should discuss the findings with the technologist and your attending if necessary. It is your job is to find out the clinical story by contacting the physician who sent the smear and let them know your findings. Manual differential/Band count: Manual differentials are performed for selected criteria by the hematology lab. These criteria are based on the white count, automated differential results (and flags by computer), and comparison with previous results. You may be called by a clinician who feels a manual differential is indicated for their patient. You should find out the indication for the manual differential and explain to them the difference between a manual (100 cells, labor intensive) and automated differential (thousands of cells, not good at low WBC <1.5). See Pierre RV. Peripheral blood film review. The demise of the eyecount leukocyte differential. Clin Lab Med. 2002 Mar;22(1):279-97. Pdf version is available on the Intranet http://info.med.yale.edu/labmed/intranet/files/oncall/Manual/ A one time band count is appropriate only as part of a sepsis work-up in patients less than 3 months of age. See Cornbleet PJ. Clinical utility of the band count. Clin Lab Med. 2002 Mar;22(1):101-36. Pdf version is available on the Intranet http://info.med.yale.edu/labmed/intranet/files/oncall/Manual/ In neutropenic patients (<1.5), manual differentials are done Monday, Wednesday, and Friday. The clinicians may not be aware of this and sometimes if they call on a Tuesday and you tell them this, they will be happy with that. It is helpful in borderline cases to tell the clinician that you will check out the automated differential and see if there were any flags and then discuss it further with them. Lastly, sometimes the clinician may feel there could be “something wrong” with the automated differential (i.e. it doesn’t match previous diff or previous history) and then a manual differential can be done to check it. Manual differentials can only be performed on a recent (collected in the last 4 hours specimen) since the WBC will degenerate. D-Dimer The Hematology Lab offers two different D-Dimer assays: D-Dimer and D-Dimer (Thrombosis). The standard D-Dimer test is for DIC. The D-Dimer (Thrombosis) is for ruling out PE in patients with low probability for PE in the ED. The regular D-Dimer should not be used for rule out PE and the D-Dimer (Thrombosis) should not be used for inpatients. It is okay to approve the D-Dimer (Thrombosis) for an outpatient if there is low probability for PE (based on clinical assessment such as Wells criteria). Microbiology Gram stain Microbiology is open until 12 midnight and will do gram stains up until then. However, there are rare occasions when a gram stain is requested after midnight and before 6 am when Micro re-opens. Hematology technologists can usually see bacteria on a Wright stain and gram stains can be performed by the hematology technologists if it is indicated. Your job is to find out the indications and if it is needed before microbiology re-opens. See e-mail from Dr. Edberg below Date: Wed, 13 Apr 2005 18:11:31 -0400 From: John M Fisk <john.fisk@yale.edu> To: “Bennett, Jonathan” <jonathan.bennett@yale.edu>, “Fisk, John” <john.fisk@yale.edu>, “Eid, Tore” <tore.eid@yale.edu>, “McCalip, Benjamin” <benjamin.mccalip@yale.edu>, “Genzen, Jonathan” <jonathan.genzen@yale.edu>, “Tzou, Abraham” <abraham.tzou@yale.edu>, “Tian, Shulan “ <shulan.tian@yale.edu>, “Oethinger, Margret D.” <margret.oethinger@yale.edu>, “Tormey, Christopher” <christopher.tormey@yale.edu>, “Pelletier, Joseph P.” <joseph.pelletier@yale.edu>, “Transue, Sarah “ <sarah.transue@yale.edu>, “Browne, Frederick A “ <frederick.browne@yale.edu>, “Torres, Richard “ <richard.torres@yale.edu>, “Klein, Roger “ <roger.klein@yale.edu>, “Ripps, Michael E., M.D., Ph.D.” <mripps@vzw.blackberry.net> Cc: “Rinder, Henry M.” <henry.rinder@yale.edu>, “Edberg, Stephen “ <stephen.edberg@yale.edu> Subject: [Fwd: Re: Gram Stains] Another page in your on-call notebook... Hi folks, Recently, Ed Sullivan (the Hematology Lab Manager) asked for help regarding the apparent increase in “off-hours” requests for gram stains. In the past couple weeks, there have been requests for gram stains -- sometimes on tissue specimens, and on at least one occasion in which the initial Wright-Giemsa stain was negative -- and the approval for gram staining under these circumstances has been called into question. In order to ensure that these cases are handled appropriately (especially at 2 AM when most of us loathe the notion of having to call an attending), I posed the question to Drs. Edberg & Bia with a request for guidance. The salient issues include: 1) should gram stains be performed on specimens for which a Wright-Giemsa stain has already been performed? 2) is it advisable to open a “sterile” specimen container in order to perform a gram stain, and thereby potentially contaminate it? 3) should the hematology lab handle non-fluid specimens (such as soft tissue specimens)? Dr. Edberg addresses all of these issues in his email below. Please read it carefully and make sure that you clearly understand the issues and feel comfortable with how to handle these requests. For those of us with “2 AM syndrome”, it might not hurt to print this and stick it in your on-call notebook in case you need a quick refresher in the wee hours of the morning. The only other thing to add to his note is that the on-call resident probably ought to: 1) call the Micro Lab once there is a reasonable certainty of there being someone there and willing to pick up the phone (probably by 6:30 AM), and let them know if there is a specimen that needs urgent attention 2) as always, sign the case out to the Micro resident and/or the fellow thanks! John -------- Original Message -------- Subject: Re: Gram Stains Date: Tue, 12 Apr 2005 14:47:56 -0400 From: Stephen Edberg <Stephen.Edberg@yale.edu> To: John M Fisk <john.fisk@yale.edu>, “Bia, Frank” <frank.bia@yale.edu> CC: Edmund Sullivan <Edmund.Sullivan@ynhh.org>, “McPhedran, Peter “ <peter.mcphedran@yale.edu>, “Rinder, Henry M.” <henry.rinder@yale.edu> References: <s25aa5ad.065@mercury.mis.ynhh.com> <425BDC6E.7060707@yale.edu> John, The WG stain will detect bacteria and fungi with at least the same sensitivity as the gram stain (and could actually be better). Hematology uses the cytofuge to prepare the smear (assuming CSF or urine), which is the most sensitive method. Therefore, for the detection of bacteria and fungi, this is sufficient. When reporting the WG stain it is imperative, especially when speaking on the phone to someone, to be absolutely clear that the WG stain does not differentiate Gram positives from negatives. Therefore, if the WG stain is negative for bacteria and fungi, there is no point in doing a Gram stain. If the WG stain is positive (and note, be careful how that word is used. We once had a resident report “I’m positive there are cocci” which was taken by the listener as “positive cocci”, and they weren’t) what to do? First, it is a clinical decision. If the results of the gram stain will modify therapy, I believe it should be done. The resident can ask this question. For example, if cocci are seen in the CSF in a primary meningitis, ceftriaxone will be used for all microbial candidates (unless there is something odd in the history). Unless special circumstances, a Gram stain is not necessary. If positive rods, Listeria must be entertained. The resident should be able to ascertain the answer to this question. Second, all the Hematology technologists are ASCP, and can do a gram stain. It is particularly important to perform a control on the slide, since they may not do them frequently. The best control is a swab of the inner mouth. The gram stain can be done from the Hematology specimen, or from the Chemistry specimen, so there should be no contamination issue. If the Micro specimen must be used in a particular case, a sterile 0.01 urine loop and gloves will keep it “sterile enough”, since we are not looking for skin contaminants (except from patients with shunts). Some hospitals, and all commercial labs, have generalists at night. We used to have a night technologist but he was removed in a budget cut. I think we should have generalists at night for issues like this and general efficiency, and for the blood culture machine. Just a management note for the residents. Regarding tissue specimens: these need be emulsified in a sterile mortar/pestle apparatus, so Hematology really can’t do this. Lastly, we arranged Micro’s schedule so that someone arrives at 6 a.m. SCE At 10:34 AM 4/12/2005, John M Fisk wrote: > Under what circumstances should a specimen be left until it can be > processed in Micro? > > Under what circumstatnces should a gram stain be performed, even if > it means potentially contaminating the specimen in the process? > > Are there circumstances in which a WG stain would NOT pick up an > organism that a gram stain would? (with the obvious proviso that a WG > stain cannot allow differentiation of gram positive vs gram negative) > > > 3) tissue specimens have been received with a request for a gram > stain: the Hematology lab is simply not set up to perform gram stains > on these types of specimens. -- John M Fisk, M.D. Administrative Chief Resident, Department of Laboratory Medicine Yale University School of Medicine, New Haven, CT pager: (860) 588-8971 phone: (203) 737-2088 Immunology Immunology is not open in the evenings or on the weekends. You can get the key for the laboratory in Flow Cytometry if you need reports that are filed in Immunology (IFE, Factor V Leiden, Prothrombin, MTHFR, lymphocyte proliferation, colony stimulation assays) or to access the card file that has all the send out tests for Immunology. If you have questions regarding immunology tests that you cannot answer, you can call the attending on Immunology and we also a “weekend” pager worn by the manager of Immunology, Josephine. Actually, Josephine asks that you call her at home first 203-284-9924 and then if no answer try the beeper 412-0838. Viscosity/IgA There occasional requests for viscosity or IgA testing on weekends. If the viscosity would be used to determine therapy (e.g. plasmapheresis in multiple myeloma), then it should be arranged. If you get a request for an IgA level before giving IVIG, this is not typically needed before the first dose of IVIG; even if the patient was IgA deficient, anti-IgA should not be an issue without prior exposure. Virology There are very few calls for virology and nothing of any recurrent nature except for the occasional request for HIV testing in the middle of the night for patients in labor and delivery. Make sure you are familiar with the protocols for liver transplant (notifying virology), needlestick and rapid HIV test requests, SARS guidelines, and others provided by Dr. Landry. In general, the hours of virology are 7-7 M-F and 8-3 Sat. In flu season, the hours may be later into the night, but usually not past 10-12pm. VA You will be called by VA clinicians to approve all blood product orders except RBC’s. Transfusion audit criteria are included below: Other miscellaneous calls from the VA can be handled very similarly to calls at Yale. Requests for myobacterial blood cultures: green top tube. (At Yale it’s a light blue top/citrate) Chemistry Critical Values: In the Emergency Department, these are usually Toxicology cases and Dr Hodsdon’s handout should provide all the necessary background information necessary. Read the section pertaining to the issue you are called about prior to calling the ER, this will help you to assist the clinicians if necessary. The chemistry technologist will call you with the result. Get all information you can from the technologist including the test results, when the specimens were drawn, and will there be any other confirmatory tests done. Ask if there were other negative toxicology results as well. Usually the actual results have already been reported to the ER by the technologist, but you should have an MD to MD conversation. Tell the clinician the result and say you wanted to make sure he/she was aware of it. Then say you are interested in following up the results and would like to obtain some clinical history. Also offer any assistance in interpreting the results (i.e. esp TCA results) or further laboratory work-up. If there will be follow-up or confirmatory tests done automatically by the lab, let the clinician know. You can remind them there is a clinical toxicologist (641-Toxi, Dr. Carl Baum; Dr. Asim Tarabar another option) available if they need a consultation for unusual cases. Questions for patients outside YNHH should be referred to Poison Control (1-800-222-1222). Other critical values may be reported to you from any lab. These are usually in situations where the laboratory cannot reach the ordering physician. Critical values must be report by law. You basically have to chase someone down to report the results to. Most clinics and doctor’s offices have someone on call (the page operator can help x83111) and it is sufficient to report the results to an on-call person. Get the name of the person to whom you reported the results and give that name to the lab to enter into the computer. Also, if possible, obtain a clinical history. Off hours drug levels: Requests for off hours drug levels can be handled by getting the clinical indications for the test from the clinician. Then speak with Chemistry and find out the usual schedule for the test. If the clinician can wait for the usual run, that if fine. However, if they need an emergent drug level and there is mutual feeling that it is indicated, then speak with chemistry to see it there is sufficient technical staff/expertise to do the test. If any test in chemistry is truly indicated, a technologist can be called in. You should consult the attending in these cases. Urine Drugs of Abuse testing: Dr Hodsdon has provided another handout on the urine drugs of abuse panel which is very helpful. Occasionally, you will have to help someone interpret results of these screens. Dr. Hodsdon’s pdfs are available on the Lab Medicine Web site http://info.med.yale.edu/labmed/protected/lectures.html username = resident, password = path0l0gy Pheochromocytoma/Neuroblastoma Many tests exist for pheochromocytoma (urine/plasma, 24 h/spot, catecholamines/metaphrines/VMA). Based on institutional practice (Dr. Donabedian), the standard work-up for pheochromocytoma at YNHH is a 24 hour urine for catecholamines and VMA. Other options we send out to Mayo include plasma free metanephrines (touted as single best test for screening in a 2002 JAMA article; may be more sensitive but less specific) and 24 hour urine metanephrines. Dr. Donabedian would not approve of plasma catecholamines to be sent out. For neuroblastoma, urine should be tested for catecholamines and HVA. 24 hour urine is not required for pediatric patients. Porphyria It is typically sufficient to know that 24 hour urine for porphobilinogen should be ordered for acute intermittent porphyria (neurovisceral symptoms) and that 24 hour urine for porphyrins should be ordered for porphyria cutanea tarda (photosensitivity). The elevations in different metabolites reflect different blocks in the pathway. For details on the metabolic pathway and other types of porphyria, check a reference source. 1
Manual is available online http://info.med.yale.edu/labmed/intranet/files/oncall/Manual/ http://info.med.yale.edu/labmed/intranet/files/oncall/Manual/ManualContents.txt Phone list is available online http://info.med.yale.edu/labmed/intranet/files/ On Call Primer is available online http://info.med.yale.edu/labmed/intranet/files/orientation/ Computing folder has info on how to access the Intranet/FTP, YNHH labs from home, BB database, VA VPN, Yale library, etc. http://info.med.yale.edu/labmed/intranet/files/computing/ http://info.med.yale.edu/labmed/intranet/files/computing/ComputingContents.txt BLOOD BANK: The Medical Director MUST be called when any of the following conditions are suspected or proven: Acute intravascular hemolytic transfusion reaction Septic transfusion reactions TRALI New apheresis patient referral Incompatible blood is given to any patient Death as a result of transfusion Anaphylactic reaction to blood Seizures in a blood donor Inadequate blood inventory or Red Cross supply available as backup Disagreement with members of the medical staff regarding blood ordering or transfusion reaction work-up Cardiac arrest in an apheresis patient Need to switch component blood type for a patient If the thought crosses your mind...... Blood Bank Sample Labeling Policy 1)Properly identify the patient. All patients must be identified by a stamped or hand written wristband. In clinic settings only, a label may be applied to the patient’s clothing in lieu of a wristband. 2)Blood Bank samples must be drawn in pink or lavender stopper (EDTA) tubes. 3)Samples must be labeled in the presence of the patient with the following information, using a CCSS label, addressograph label, or handwritten label: Patient’s full name Patient’s Medical Record Number (or if the MRUN is not available, patient’s DOB) Date sample was drawn All samples MUST bear the first name (or first initial) and last name of the person drawing the sample. If not present, the sample will be discarded! 4)Blood Bank samples are acceptable for crossmatch for 3 days from the date drawn, with the exception of EAS samples. 5)EAS (Express Admission Surgery) samples are tested (type and screen) when drawn. The EAS sample is acceptable for crossmatching blood for surgery occurring within the next 30 days if the patient has no antibody or history of an antibody, AND has not been transfused or pregnant in the last 3 months. The EAS sample may be used for crossmatching for 3 days post-op. Blood Components and Indications for Transfusion: Packed Red Blood Cells… “Red Cells” Collection process: phlebotomy Average volume: 250 mL Storage time to expiration: 42 days, with additive solutions Storage conditions: 1-6C Hct in bag = 52-60%, expect rise in Hct 3% per unit Infusion rate: 2-4 hr Indications: SEE AUDIT CRITERIA RBCs are used to treat patients in need of increased oxygen carrying capacity. The patients are generally anemic, and they may not have the ability to produce red blood cells as a result of impaired bone marrow or renal function. Red cell transfusions should be administered based on clinical need and not based on laboratory (CBC or other) values. Platelets Collection process: Separated from whole blood after phlebotomy - random donor platelets, RDP Plateletpheresis - single donor platelets, SDP Average volume: 50 mL (RDP); 300 mL (SDP) Storage time to expiration: 5 days Storage conditions: 20-24C (room temp) with continuous gentle agitation Expected CBC increment in a non-acute hemorrhage: 5,000/L (RDP); 30,000 L (SDP) Random donor units are pooled (Yale = 4 unit pools, VA = 5 unit pools), once pooled platelets must be transfused in 4 hours or less Infusion rate: variable Indications: SEE AUDIT CRITERIA Platelets are used to treat patients who are bleeding as a result of thrombocytopenia. In the surgical or trauma setting, platelet counts below 50,000/L will be treated if the patient is bleeding. In the oncology setting, platelet counts below 10,000 to 20,000 L will be treated with platelet transfusions. In general, one does not transfuse platelets at a specific “trigger” count, but one will follow decreasing platelet count trends and administer prophylactic platelets in at-risk patients. Fresh Frozen Plasma “FFP” Collection process: Separated from whole blood after phlebotomy (frozen w/in 8 hrs.) Average volume: 220 mL Storage time to expiration: 1 year Storage conditions: frozen at temperatures below (-18C) Expected increment in a non-acute hemorrhage: A typical dose of FFP is 2-4 units. One can expect an increase in all coagulation factors by 10-20% with this dose. Must be thawed then transfused within 24hrs, Provides all coagulation factors, dose of 10-20 ml/kg expect 20% increase in factors Infusion rate: 4-10 ml/min Indications: SEE AUDIT CRITERIA FFP is used to treat patients who are bleeding as a result of global coagulation factor deficiencies. In the surgical or trauma setting, coagulation factors may be reduced due to dilution of the factors during fluid resuscitation and/or consumption due to bleeding or DIC. In the medical setting, conditions such as liver disease and vitamin K deficiency can result in a decreased production of coagulation factor proteins. For management of elevated INR, see American College of Chest Physicians (ACCP) guideline especially Table 6 [Ansell J, Hirsh J, Poller L, Bussey H, Jacobson A, Hylek E. The pharmacology and management of the vitamin K antagonists: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest. 2004 Sep;126(3 Suppl):204S-233S. Erratum in: Chest. 2005 Jan;127(1):415-6. dosage error in text.] Pdf version is available on the Intranet http://info.med.yale.edu/labmed/intranet/files/oncall/Manual/ Cryoprecipitate Collection process: Separated from whole blood after phlebotomy, prepared from FFP thawed at 1-6 C, supernantant plasma is removed and remaining precipitated proteins and small amount of plasma remain as “cryo”. Average volume: ~15cc each unit Storage time to expiration: 1 year Storage conditions: frozen at temperatures below (-18C), thawed at 1-6 C, then kept at 20-24C, should be transfused within 6 hr of thawing and 4 hr of pooling. Infusion rate: 5-10 ml/min Indications: hypofibrinogenemia, Factor XIII deficiency, von Willebrand’s disease, hemophilia A, uremic bleeding Cryo is rich in VWF, Factors VIII and XIII, fibrinogen, and fibronectin, expect fibrinogen rise to be 5mg/dl per unit of cryo. Hemostatic level of fibrinogen >100 Calculation for hypofibrinogenemia: Adult: typical dose 10 units of cryo plasma volume: 40 ml/kg (adult), Child: 80ml/Kg (TB volume x (1-hct)) Formula = Desired fibrinogen (200) – Actual Fibrinogen X Plasma volume in dL Mg/bag (200) Concerns During Transfusion of Blood Products Once any blood product is “spiked” or “opened,” the transfusion should be finished within 4 hours. This minimizes any potential bacterial growth due to contamination at the time of the “spike.” (It is also a mandate by the government and standard in the United States.) See Goodnough LT. Risks of blood transfusion. Anesthesiol Clin North America. 2005 Jun;23(2):241-52. Pdf version is available on the Intranet http://info.med.yale.edu/labmed/intranet/files/oncall/Manual/ Transfusion Reactions: See Transfusion reaction section Transfusion Transmitted Diseases “TTD” Transfusion 1. Needle: 18 gauge or larger; if veins too small, use 23 gauge or larger, but slower flow rate (watch out for hemolysis) 2. Filter: standard 170 micro in line filters to trap cellular debris and coagulated proteins 3. Blood warmer: <42C 4. No mix with iv medication, except: normal saline, 5% albumin, plasma protein fraction. Jehovah’s witnesses: we do not have blood substitutes. The Associated Jehovah’s Witnesses for Reform on Blood http://www.ajwrb.org/ does not represent mainstream Witness views. However, they do refer to the general Witness policy that red cells, white cells, plasma, and platelets are NOT acceptable, but fractions are a personal choice. See commentary on June 2004 WatchTower figure http://www.ajwrb.org/6-15-04.shtml Use of Leukocyte Reduced Blood Products A leukocyte reduced blood component contains < 5 x 106 donor leukocytes per final product. Current blood filters and apheresis devices are capable of reducing residual WBC content to well below 1 x 106. Total of 109 of WBC in blood components. Prestorage leukoreduction is the preferred method as it prevents cytokine accumulation and microparticle formation and is standard practice at Yale for all red blood cell and platelet inventory. Reduce the risk of febrile nonhemolytic transfusion reactions, HLA alloimmunization, CMV transmission. Use of CMV-safe Blood Products Cellular blood components have a reduced risk of transmitting CMV Infection (“CMV safe”) if: a)They are tested and found to be sero-negative for CMV antibody or b)They are pre-storage leukoreduced, 99.9% or 3 log reduction These two methods are considered to provide equivalent reduction of risk of CMV transmission. Bedside filtration with a leukoreduction filter is not considered adequate to reduce the risk of CMV transmission. Use of washed RBC Wash with normal saline to remove 99% of plasma proteins, electrolytes, and antibodies. Used to prevent recurrent allergic reaction, anaphylactic transfusion reaction, hyperkalemia in pediatric patients, and also for post transfusion purpura. Takes 20-30 min extra time. Thawing and Deglycerolization Used when rare Ag negative RBC are used. Takes about 20-40 min, and repeated freeze-thaw may result in loss of volume. Incompatible blood administration When incompatible blood has to be given (in emergent cases or in cases of autoimmune hemolytic anemia or an alloantibody to a high incidence RBC antigen or no cross match compatible blood available), the resident should notify the clinician about the situation and let them decide to proceed with the transfusion or not , and communicate with the blood bank attending when time permits. Recommend a test dose for administration if has to be released, 15 cc in 10 min and check patient’s vital signs and status closely. Release of Uncrossmatched Blood 4-6 units of O negative red cells, tagged for emergency release, are stored in each of two Blood Bank refrigerators, one located in the ED Trauma Room (6 units) and one in the OR (4units). Also, uncrossmatched blood can be obtained directly from the Blood Bank; this can be either O negative or, if time permits and a valid current patient sample is available, type specific. The transfusing physician is responsible for signing the release form for use of uncrossmatched blood and having this form returned to the Blood Bank as soon as possible. Massive transfusion protocol can be initiated when necessary by a clinical attending, initial box in the Blood bank includes; 10 O neg RBC, 2 units of thawed FFP, 1 SDP. Uncrossmatched blood will be cross-matched retrospectively and it is the resident’s responsibility to inform clinicians if the blood was incompatible and warn about signs of hemolysis. Use of Irradiated Blood Products Cellular blood components are exposed to gamma radiation to prevent the proliferation of T lymphocytes which can lead to transfusion asssociated graft vs host disease (GVHD), especially in immunosuppressed or neutropenic patients or patients with hematologic malignancies and dysfunctional immune systems. When a patient is at risk for GVHD, all cellular components, RBCs, platelets, and granulocytes, must be irradiated. In addition, components from a blood relative (direct donation) or HLA-matched donor must be irradiated (except hematopoietic progenitor cells). Similarity in HLA may result in survival of transfused lymphoctyes and thus lead to GVHD. Irradiation of with a minimum dose of 2500 cGy is recommended by AABB and FDA standards. It requires a few minutes at Yale, but may take several hours for VA, due to transportation time. After irradiation, expiration time becomes 28 days, and with increased K leakage, (wash for Exchange transfusions for infants). A good review of TA-GVHD is Schroeder ML. Transfusion-associated graft-versus-host disease. Br J Haematol. 2002 May;117(2):275-87. Pdf version is available on the Intranet http://info.med.yale.edu/labmed/intranet/files/oncall/Manual/ Check the Resident Blood Bank Manual to see the current YNHH SOP for irradiation. From the 2005-2006 version on the Intranet http://info.med.yale.edu/labmed/intranet/files/oncall/BloodBankManual/ Indications for irradiation of cellular blood components include: products A. All directed donations of cellular components B. All cellular components for use in the Newborn Special Care Unit C. All cellular components for all children under four months of age D. All cellular components for infants undergoing extra-corporial membrane oxygenation (ECMO) E. All single-donor platelets or granulocytes DIAGNOSIS / DISEASE STATE A. Congenital Immune deficiency B. Acute leukemia C. Lymphoma D. Neuroblastoma, rhabdomyosarcoma, glioblastoma multiforme E. Patients who have received or are about to receive peripheral blood stem cell transplants or bone marrow transplants (allogeneic or autologous) F. Donations from blood relatives G. Any patient receiving high dose immunosuppressive chemotherapy such as Cytoxan and Fludarabine H. Solid organ transplants. For details, refer to SOP BB 6.14, Solid Organ Transplants I. Myelodysplastic Syndrome Other requests will be discussed first with a Blood Bank physician. This includes requests for patients with aplastic anemia, but only if receiving or within one month of having completed ATG. Irradiated products are suitable for any patient, even if they do not require it. AIDS is not an indication for irradiation. See Schroeder ML review about no cases of TA-GVHD in AIDS. Transfusion Reaction Workup All adverse reactions associated with blood transfusion must be reported to the Blood Bank by the clinical service performing the transfusion. Responsibilities of the Clinical Service administering the transfusion: Stop the transfusion immediately. Keep IV open with a suitable solution such as 0.9% NaCl. Report at once to the responsible physician and to the Blood Bank. Send freshly drawn and properly labeled lavender top tube, component bag, all attached IV lines and fluids, and transfusion reaction form (F1934) (can be ordered in CCSS, order/blood bank/transfusion reaction evolution, the only copy should be printed out automatically when the order is finished) to the Blood Bank at once. (see example) One exception to the above is a MILD allergic reaction presenting with a localized rash (hives) ONLY. In this instance, the patient can be treated with an antihistamine (Benadryl) and the reminder of the unit can be infused if the symptoms disappear and no fever, chills, or cardiorespiratory signs or symptoms occur. Blood Bank Technologist’s Work-up of Transfusion Reactions: Perform clerical check to assure that the blood was issued/ transfused to the correct patient. Examine post-transfusion specimen for hemolysis. Perform ABO/ Rh, DAT testing on post-transfusion specimen. Fill out the front of the “Transfusion Reaction Workup” form (Form 1933) Resident’s Work-up of Transfusion Reactions: Initial call check list: Is the patient stable? How bad is the reaction? If there are signs of: Hemolysis Very high temp SOB Increased O2 requirement Bronchospasm Hypotension DIC Call the attending right away! Why is the patient in the hospital? Is the patient bleeding, how and from where? How many units were transfused, when started, when stopped? How much of the unit was transfused? Need more transfusion right away? Pre and post transfusion vitals Pre and post transfusion labs Transfusion reaction work-up check list Make sure the form of transfusion reaction evaluation is sent by the physician Finish the work-up form Obtain the yellow compatibility tag and return to chart Finish the audit form Fill out and sign the sticky Ask the attending to sign all the forms Put the sticky OR a note into the chart ASAP. A notation must be made on the patient’s chart regarding the outcome of the work-up within 24 hours. For this purpose, the resident should contact the Blood Bank Medical Director by phone to review the reaction if it occurs on a weekend. The resident will make an initial diagnosis of the type of reaction. The resident is also responsible for determining if subsequent transfusions may be given once the workup is complete. If the resident has difficulty making a definitive diagnosis of a transfusion reaction, the Blood Bank Fellow on call or the attending on call MUST be consulted. TYPES OF REACTIONS: Acute hemolytic transfusion reaction: The first job is to rule out an acute hemolytic transfusion reaction based on Blood Bank laboratory tests (negative DAT and the absence of hemolysis). The sine qua non of an acute intravascular hemolytic reaction is red plasma and red urine- hemoglobinemia and hemoglobinuria. Both must be present. A plasma hemolysis usually looks pink when the level is > 20 mg/dL. If hemolysis is suspected, additional tests can be ordered (plasma and urine hemoglobin, LDH, indirect and direct bilirubin, and haptoglobin). Management of an acute hemolytic transfusion reaction includes monitoring the urine output to ensure that it is at least 100 mL/hr for 18-24 hours. Treatment with IV normal saline should be initiated. Remember, hydration should be performed judiciously in patients with cardiac failure or renal failure. Diuretics are helpful to improve renal perfusion. If no diuretic response occurs after several hours, acute tubular necrosis should be evaluated. Avoid diuretics in patients with compromised renal function. Febrile non-hemolytic transfusion reactions (FNHTR) are a temperature rise greater than 1C, possibly accompanied by chills, that occurs during or up to 2 hours after a transfusion and is not attributable to another cause. FNHTR are caused by antibodies to leukocyte antigens or cytokine infusion. It is a diagnosis of exclusion. Determine if the patient has had recent fevers by reviewing vital signs in the hospital chart. If fevers occurred prior to reaction, determine what etiology is most likely and document the frequency of occurrence. If symptoms (e.g., shaking chills) accompanied the suspected transfusion reaction, did these symptoms also occur prior to transfusion? The treatment of a febrile non-hemolytic reaction includes an antipyretic such as acetaminophen. Recommend future premedication with acetaminophen if suspect a febrile non-hemolytic reaction. Review all cases with the Blood Bank Medical Director. Allergic Reactions are associated with symptoms vary from urticaria, hives, itching to anaphylaxis and may occur up to2-3 hours after a transfusion. They are likely caused by antibodies to plasma proteins or rarely antibodies to IgA. Document the extent of rash and any additional symptoms. Determine if there was difficulty breathing and if it was associated with throat swelling (laryngeal edema). A mild localized urticarial-pruritic rash should be treated with Benadryl, 25-50 mg (adult dose). IF THIS IS THE ONLY SIGN AND SYMPTOM and if it goes away after treatment, the same unit of blood can be given safely. For patients with frequent allergic reactions it should be recommended that they are pre-treated with an antihistamine (Benadryl) for subsequent transfusions. If a patient who has never received a blood product has an anaphylactoid allergic reaction, consider testing for IgA deficiency. The treatment for anaphylaxis includes stopping the transfusion and administering epinephrine. Oxygen therapy and possibly corticosteroids are also helpful. Intubation and pressors may be needed if shock occurs. Circulatory overload is manifested by pulmonary edema associated with blood transfusion. This typically occurs in patients with a history of congestive heart failure or the elderly. Diuresis or phlebotomy should be considered. Transfusion-associated sepsis is seen when transfused blood products are contaminated with bacteria. Usually manifests as fever, chills, rigors, shock. If septic transfusion reaction is suspected, specimens from both the patient and the transfused unit should be sent for gram stain and culture. Transfusion-related acute lung injury (TRALI) is caused by donor antibodies against recipient HLA or leukocyte antigens which lead to leukoagglutination and occlusion of the microvasculature of the lung. The patients present with dyspnea, fever, chills, respiratory failure and a cxr that shows pulmonary edema. Treatment is supportive and the donor units should be quarantined until etiology established. Hypotensive reactions appear to involve the generation of kallikrein by some types of biomaterials (especially bedside filters) leading to bradykinin production which in turn can lead to hypotension. Patients on ACE inhibitors are at greater risk for this complication. Massive transfusions can cause citrate toxicity, generally manifested as symptoms of hypocalcemia. Other reactions: Hypokalemia Hyperkalemia Hypothermia Serology Work-ups/New Antibody: The blood bank will call when a new antibody is found on an antibody screen and panel work-up. It is the resident’s responsibility to find out the medical and transfusion history of the patient and talk with the clinician regarding the findings. A notation should be made in the chart. An example of a note follows: Blood Bank Resident Note The antibody screen was positive on __________. Anti- _______ was identified in the serum. The DAT was _______. The auto-control was _______. The patient was last transfused ________. At that time the antibody screen was negative, and compatible red blood cells were given. The detection of anti-________ is a new finding for this patient. Anti- _______ antibodies can cause clinically significant hemolytic transfusion reactions; therefore, all future transfusions should be ________-negative red blood cells. The patient can be monitored for signs of hemolysis by checking the Hematocrit, LDH, Bilirubin, BUN and Creatinine, and urinalysis. Consult the following paper on the clinical significance of antibodies. Thrombocytopenia/Platelet Refractoriness Thrombocytopenia Check list: Is the patient on anti-platelet medication? Is the patient post-op? Is the patient uremic? Is there Active bleeding? How much? What was the last platelet count? Do you have post-transfusion platelet counts? Is the patient febrile? Does the patient have a big spleen? 1) A patient who is refractory to platelet transfusions can be evaluated by determining if there is a sufficient increase in platelet count, sampled between ten minutes and one hour after transfusion. If there is not a sufficient response to platelet transfusion immediately, and if the patient does not have sepsis, splenomegaly, DIC, massive bleeding, drugs causing thrombocytopenia, fever, the refractory state may be due to immune clearance (HLA or platelet antibody) of the transfused platelets. Crossmatched or HLA matched platelets may be helpful for patients who have alloimmune platelet refractoriness. 2) A sufficient increase in platelets after transfusion can be determined by calculating the corrected count increment (CCI) for a sample drawn 10 minutes to 1 hour after platelet transfusion. An acceptable CCI = >7.5x109/L for a sample drawn 10 minutes to 1 hour after infusion. For a sample drawn 18 to 24 hours after infusion, >4. 5x109/L is considered acceptable. CCI = (platelet countpost/L - platelet countpre/L) x Body Surf. Area (M 2) Number of platelets transfused ( in multiples of 1011/L) Note: Single donor platelets ~ 3.0x1011 Random donor platelets ~ 0.6x1011 x number of units in pool (~ 4) 3) A CCI less than 4,000-5,000/L is a decreased response to platelet transfusion. This decreased response in the early time period after platelet transfusion is characteristic of immune clearance in a patient who is refractory to transfusion. A low CCI value calculated for two different platelet transfusions warrants the Blood Bank sending a sample (one EDTA purple tube) to the Red Cross for platelet antibody screen. If positive, a crossmatch compatible single donor platelets should be used for the patient. Even HLA compatible or crossmatch compatible platelets may not produce a good CCI in a refractory patient. “Platelet Drip” Infusions Continuous platelet infusions, “platelet drips,” have not been formally studied to validate their effectiveness as an alternative to the standard method of infusing platelets. There are times when a patient receives multiple platelet transfusions, and the benefit or rationale for the transfusions is questionable. If additional platelet transfusions are requested, the resident may recommend a platelet drip as a method of conserving platelets. Conservation of platelets may be needed to ensure an adequate supply of platelets for potential patients who would benefit from platelet transfusions. The maximum order for a platelet drip is 3 units given over four hours. Consult with the Medical Director, or his designee. Coagulation Factor Concentrates 1) Factor VIII concentrates are now used instead of cryoprecipitate for patients with Hemophilia because Factor VIII concentrates are processed or manufactured to reduce or eliminate the risk of TTD. The dose of Factor VIII depends on whether the therapy is prophylactic or, if for bleeding, the nature and severity of bleeding. The dose is calculated based on the patient’s measured factor VIII level. (Cost ~$1/unit) Dosage required (IU) = PV x [desired level (%) - initial level (%)] 100 where plasma volume (PV in mL) = 40 mL/kg x body weight (kg) The half-life of Factor VIII is 12 to 18 hours, although the half-life of the initial dose is about 4 hours because of extravascular equilibration. If the patient has had major surgery, the level of Factor VIII should be maintained above 40-50 units/dL for at least 10 days. Consult the package insert(s) for details. Factor VIII concentrate products that contain biologically active vWF (Humate-P and Alphanate) are useful for treatment of severe von Willebrand Disease. The activity of vWF in these products is measured as Ristocetin Cofactor (vWF:RCof), and expressed in IU. 1st generation recombinant : Kogenate, Bioclate, Helixate, and Recombinate 2nd generation recombinant: B-domain recombinant Factor VIII Monoclonal Ab purified Factor VIII: Monarc-M, Hemophil M, Monoclate P Other plasma derived Factor VIII concentrates: Humate P, Koate DVI, Alphanate, and Profilate: used for vWD 2) Porcine Factor VIII (Hyate:C) is indicated for the treatment of Hemophilia A patients with inhibitors to human Factor VIII (high but <50 human Bu, but very low porcine Bu, <10-20 BU) and for non-hemophiliac patients with spontaneously acquired inhibitors to Factor VIII. Very hard to get, have to contact the company, only for life threatening or limb losing bleedings. 3) Factor IX concentrates are used for Hemophilia B (congenital Factor IX deficiency or Christmas disease). Dosage required (IU) = PV x [desired level (%) - initial level (%)] 100 where plasma volume (PV in mL) = 40 mL/kg x body weight (kg) The half-life ranges from 18 to 32 hours, although the half-life of the initial dose is about 4 hours because of extravascular distribution. Therefore, a patient’s first dose is usually double the amount of Factor IX calculated. 4) Factor VIIa (NovoSeven) is a recombinant product which is indicated for the treatment of bleeding episodes in Hemophilia A or B patients with inhibitors to Factor VIII or IX, or other factor deficiency. (Cost = $1000/mg). Typical starting dose is 75 (20-90) ug/kg bolus, q 2 hours, not recommend continuous iv infusion, as less effective and more thrombosis risks. For a patient with a factor deficiency, watch out for thrombosis. Check the indication and patient status at each dose, try to prevent the wasting of the products. 5)Prothrombin complex concentrates (PCC): Konyne 80, Bebulin, Profilnine SD and PropexT plasma derived concentrates containing: Factor II, VII, IX, and X. 6)Anti-inhibitor Coagulant complexes (activated prothrombin complex concentrates or APCCs): Autoplex T and Feiba VH: heat-treated, plasma-derived anti-inhibitor concentrates that have a high content of factors VIIa, IXa and Xa. Used to treat bleeding in patients with FVIII inhibitors. Thrombosis risk. Treatment for vWD: Humate P (lyophilized, pasteurized, concentrate of human plasma derived FVIII and vWF; Koate DVI (Double Viral Inactivated), FVIII concentrates purified from pooled human plasma which is solvent detergent treated; Alphanate, extracted from human plasma. Treatment for Hemophilia B: recombinant FIX (rFIX; BeneFix) and two plasma-derived FIX products, Alphanine and Mononine. Package inserts for NovoSeven, Advate, Helixate, FEIBA, Humate-P, and Benefix are available online (Google search); latest versions as of Spring 2006 are on the Intranet http://www.us.novoseven.com/content/us_vers/downloads/0804NovoSevenPI.pdf http://www.advate.com/images/pdf/prescribing_info_english.pdf http://www.zlbbehring.com/ZLBB/binary/HelixateFSPI.pdf http://www.hemophiliagalaxy.com/pdfs/therapies/Feiba.pdf http://www.humatep.com/pdf/HumateP_PI.pdf http://www.hemophiliavillage.com/benefix_product.asp Rh Immune Globulin If an Rh negative patient (including a mother) is exposed to Rh positive red cells, the development of antibody to the D antigen can be prevented by administering Rh Immune Globulin (RhIG). Exposure to Rh positive red cells can occur through transfusion of platelets or granulocytes, or through pregnancy. A patient who is deliberately given units of Rh positive red cells (as in an emergency), is not a candidate for RhIG by virtue of the volume involved. WinRho is an IV preparation, obtainable in various sizes from the Pharmacy; RhoGam is for IM injection only and is stocked by the Blood Bank. Rh immunoglobulin should be given within 72 hours of exposure to D positive cells. It is considered malpractice to not treat an Rh negative mother (who has not previously formed anti-D) with RhIG at clinically appropriate times during pregnancy and at delivery of an Rh positive (D) baby. A patient’s Blood Bank serologies will be affected after receiving any RhIG: the direct antiglobulin test (DAT) might be positive because of the presence of the RhIG attached to D positive red cells; the antibody screen/panel will be positive because of the circulating RhIG. A single dose of RhIG (300 g) prevents sensitization to the D antigen in < 30 mL of whole blood (or 15 mL of red cells). If the volume of exposure is greater than 30 mL of whole blood (15 mL red cells), additional RhIG needs to be administered. The total dose of RhIG (300 g) is determined by dividing the estimated volume of the whole blood exposure by 30 (the volume of whole blood neutralized by one dose) or the estimated volume of the red cell exposure by 15 (the volume of red cells neutralized by one dose). Consult the PDR or RhIG package insert for specific dosing requirements. 1.Transfusion of Rh positive platelets or granulocytes: RhIG should be given to Rh negative patients who receive Rh positive platelets or granulocytes. The physician must be notified of this in advance so that he/she can reconsider the need to transfuse any blood products. Although Rh immunoglobulin is a relatively safe medication, the physician should have the opportunity to consider the implications of the transfusion in advance. IM preparations (RhoGam) can be problematic if a large dose is needed, IM administration is contraindicated, or if the patient has cardiac disease (can interfere with the laboratory tests for MI), and the patient is thrombocytopenia to begin with. For these reasons, WinRho might be recommended because it can be administered IM or IV. It is available in smaller doses, such as 120 g. Larger doses can be administered, at a rate up to 600 g Q 8 hours IV, until the total dose is given. If you recommend WinRho, the resident should be informed that it is non-formulary and they will not be able to order it through the CCSS system. The resident should call the pharmacist to facilitate the order. A single random donor unit of platelets, even when prepared properly, can have as much as 0.5 mL of red cells. (This is the worst case and the unit would be bright red. Most units have far fewer red cells, but always assume the worst case amount.) Thus, in a 4 unit pool, there possibly might be as much as 2 mL of red cells. Since one RhIG dose (300 g) is sufficient to neutralize 15 mL of D positive red cells, the patient might receive 7 1/2 pools of platelets (4 units each), representing a total of 30 units of single random donor platelets. The physician should be advised to administer another dose when more platelets are to be transfused. Consult with the Medical Director or designee when RhIG is administered for treatment due to receipt of Rh positive platelets. A unit of single donor apheresis platelets (“Platelets, Pheresis”), might contain as much as 5 mL red cells, so 1 dose of RhIG would only cover 3 units of this product. 2.Maternal exposures: An Rh negative mother of a D positive infant must receive RhIG within 72 hours of delivery. A full dose of 300g is usually prescribed. Testing for fetal-maternal hemorrhage: The rosette test is used to screen Rh negative women (should be done for all Rh negative woman post delivery) for a maternal-fetal hemorrhage (MFH) larger than 10 mL of Rh positive cells. A Kleihauer-Betke acid elution test is done if the rosette test is positive. It quantifies the extent of MFH by estimating the percentage of fetal cells present in the mother’s red cell volume. The result is reported either as % or as No. per 105. See Hematology section for calculation of RhIg dose. Massive Transfusion This is defined as the infusion of blood and components in amounts approaching or exceeding one blood volume (about 12 units) over a 24 hour period. Management of this situation includes assessing the available blood inventory to support the patient. Determine if it is necessary to switch the patient from type-specific to type-compatible blood products, especially for Rh negative patients. It is also important that the resident plays an active role in screening for DIC and to expedite Hematology Lab results. Suggest that the PT, PTT and fibrinogen (always done with a PT, PTT even it may not be reported) be checked if this has not already been done and make the hematology lab aware that the results are needed promptly. Make sure the clinical team considers the need for platelets, FFP and cryo as well as RBC’s. Communication between the Trauma/ Anesthesiology physicians and the Blood Bank is critical. All of these decisions MUST be made in conjunction with the Blood Bank staff and the Medical Director. DO NOT WORK in a VACUUM. Apheresis: Therapeutic and Donor The resident’s role in apheresis includes medical evaluation of the patient and need for apheresis, obtaining informed consent, and supporting the nursing staff during apheresis Indications for Therapeutic Apheresis 1) Emergency: There are three common indications for emergency apheresis: Acute chest syndrome due to sickle cell disease TTP Blastic Hyperleukocytosis 2) Other indications: Sickle cell syndrome Cryoglobulinemia Neurologic disorders: Myasthenia Gravis Gullain-Barre Syndrome Other neuropathies may respond, including chronic inflammatory demyelinating polyneuropathy and stiff-man syndrome. The Journal of Clinical Apheresis Volume 15 Issue 1-2, 2000 (1-159) Special Issue: Clinical Applications of Therapeutic Apheresis provides a good overview of therapeutic apheresis. Pdf versions including indication categories are available on the Intranet http://info.med.yale.edu/labmed/intranet/files/oncall/Manual/ Apheresis Responsibilities: (In conjunction with the Medical Director and the nursing staff): a) Before the procedure: Confirm the indication for the requested procedure. Assess the vascular access to determine if a Quinton central line or internal jugular catheter is needed. The Quinton line needed is a stiff-walled double- lumen apheresis/dialysis catheter, placed in the internal jugular or subclavian vessel. Usually the size is 11 french for adults and 7-10 french for kids Obtain height, weight and vital signs of the patient Evaluate the risk of complications. Determine the replacement fluids to be used (5% albumin/ NaCl for all but TTP patients). Evaluate medications: Patients using ACE inhibitors may experience a hypotensive reaction, particularly if albumin replacement is used in the apheresis procedure. ACE inhibitors should be stopped immediately if apheresis is started and another antihypertensive substituted. Obtain all pertinent laboratory studies. Obtain consent from the patient after explaining the possible side effects and informing him/ her of the risks of any infused blood products. If the procedure is emergent, see the Medical Director. a) During the procedure: Monitor for hypovolemia. It should not occur with continuous flow devices, but the volumes infused and returned must still be monitored closely in patients with cardiac disease or the elderly. Monitor for hypocalcemia- the citrate in the ACD-A anticoagulant will lower the patient’s ionized calcium level. FFP, hypomagnesemia, hyperventilation and hypothermia will exacerbate this citrate-induced drop in calcium. The symptoms of hypocalcemia include perioral paresthesia, tingling and numbness in the limbs, Chvostek and Trousseau signs. Apheresis General Information Stem Cell Collection 1) Peripheral Blood Stem Cells are collected for hematopoietic rescue of a patient following myeloablative chemotherapy or radiation therapy. Hematopoietic stem cells are mobilized into the peripheral blood following administration of chemotherapy and/or hematopoietic growth factors and are collected by apheresis. Both autologous and related allogeneic donors are collected at YNHH. 2) The resident’s role in the collection of peripheral blood stem cells from an autologous or allogeneic donor is similar to that for other apheresis procedures (see the preceding section). In addition, the resident should be available to expedite the patient’s and the product’s (from previous collections, if available) CD34+ counts from the Flow Cytometry Laboratory and to have the results available for discussion at Blood Bank rounds. At the time of collection, the resident is expected to consult with the attending physician to complete the PBSC Pheresis Product Worksheet, which gives processing instructions to the Blood Bank/Stem Cell Laboratory personnel as to whether the final product is to be split, frozen, and/or CD34+ selected. Plasma Exchange 1) TTP: Plasmapheresis is an extremely important and effective treatment for this disorder. Replacement fluids can include either cryopoor plasma, fresh frozen plasma, or solvent-detergent plasma. The therapeutic benefit may relate to the removal of high molecular weight monomers of von Willebrand factor. Treatment of TTP is a medical emergency. 2) Neurologic disorders: Myasthenia Gravis--Plasmapheresis is used to treat acute exacerbations. A general treatment schedule is 5 or 6 procedures over 1-2 weeks. Gullain-Barre--Early treatment is beneficial. 200 mL/kg are exchanged over 7 to 14 days. Other neuropathies may respond, including chronic inflammatory demyelinating polyneuropathy and stiff-man syndrome. Albumin generally is used as replacement fluid for these conditions. Cryoglobulinemia: Apheresis is useful to treat acute exacerbations caused by elevations of cryoglobulins which cause vasculitis, vascular occlusion, skin ulceration, nerve damage and coagulation abnormalities Cytapheresis Erythrocytapheresis 1) Sickle Cell Syndrome: A full exchange transfusion can be done, called erythrocytapheresis. This method exchanges approximately 6 units of rbc’s and is a more aggressive treatment then a partial exchange transfusion in which 2 units of blood are manually drawn and 2 units of rbc’s infused. When erythrocytapheresis is needed, the Blood Bank must be notified to prepare the units of red cells and to perform a sickle test on these units. Donated sickle trait blood must not be used because it could cause sickling within the apheresis machine. A HgbS level usually is done to determine the amount of blood that needs to be infused to reach the target of <30% hemoglobin S. A sickle column may be necessary because estimating the starting sickle cell level in the patient can result in over transfusion and unnecessary exposure to the risks of blood products. 2) For erythrocytapheresis on the COBE machine, the patient’s height, weight, hematocrit, and % hemoglobin S are needed. The requesting physician must indicate the desired post procedure hematocrit and % hemoglobin S. The Blood Bank must have a type and crossmatch and transfusion history, especially if done at another facility. 3) Emergency apheresis is not always necessary, even for a pain crisis. The procedure can be scheduled with the Apheresis Unit and Blood Bank. Sometimes only a manual exchange of two units is needed. Leukapheresis Emergency leukapheresis lowers the WBC count, although temporarily, in patients with extreme leukocytosis (blasts over 100,000/uL) due to acute myelogenous leukemia. Such high counts might cause hyperviscosity syndrome. Thrombocytapheresis Maternal platelets often are used to treat NAIT. Similar to HDN, NAIT results when the mother’s antibody to the infant’s platelets crosses the placenta, but unlike HDN, it often affects the first-born. The maternal plasma must be removed and the platelets resuspended in saline at a reduced volume. Allogeneic platelets can be used, if necessary, but they must lack the antigen being attacked by the maternal antibody and the plasma must be compatible with the infant’s red cells. All products must be irradiated and be CMV negative or leukocyte-reduced Granulocyte Collection 1) Neutropenic (generally < 500/uL) children or adults who have sepsis and who are unresponsive to IV antibiotics might benefit from granulocytes donated by a normal individual. 2) The donor is stimulated with G-CSF (5-10 ug/kg) and steroids (8 mg dexamethasone) PO 12-24 H before undergoing apheresis to harvest the granulocytes. A concentrate from a stimulated donor contains 4-8 x 1010 granulocytes, along with many of the other leukocytes and as much as 20-50 mL of red cells. A standard blood filter must be used (never a leukocyte reduction filter) and the product should be irradiated to prevent GVHD. 3) The granulocytes should be administered as soon as possible after apheresis because of well documented deterioration of granulocyte function (within 24 hours). Once transfusion therapy is initiated, support should continue for several days until infection is cured, defervescence occurs, the absolute granulocyte count returns to at least 500/mL, or the Medical Director and/or attending decide to halt the therapy. 4) All females of child bearing potential must have a negative pregnancy test prior to receiving G-CSF. Hematology Critical Value Reporting The policy per Dr. Rinder is that the Heme technologist tries first to have the clinic answering service page the on-call physician to the Heme lab. If there is no response after 30 minutes, critical value for CBC, Coag, etc. are referred to the on call resident for follow-up attempt to notify a covering physician. Kleihauer- Betke test: A K-B should be used primarily for determining RhIg dosing in cases of exposure to fetal blood in a Rh negative mother. In these cases, a rosette test may be sufficient if at least one dose of RhIg will be given; a K-B is only needed if the rosette is positive to determine if additional RhIg is needed. The K-B should not be used as a primary indicator of fetomaternal hemorrhage; fetal assessment by clinical monitoring and ultrasound are more important. This test is ordered to quantitatively assess the volume of fetal RBCs that are present in maternal blood. It is basically an acid elution process that washes out the HbA (leaving pale RBCs) while HbF remains resistant. A slide is examined and percentage of fetal red blood cells is reported. Rhogam is then dosed based on the percentage. The clinicians may ask you to help calculate a dose of Rhogam (RhIg) based on the K-B result: First, Calculate the maternal blood volume: 70 ml/kg x mother’s weight or use the volume of 5000 mL (assumes an average adult weight of 70 kg) Calculate the volume of fetal blood to which the mother was exposed: If K-B is 1.3% and mother’s weight is 70 kg ( 1.3 / 100 ) x 70 ml/kg x 70 kg = 63.7 mL of fetal whole blood in maternal circulation This is an imprecise measure, so it is standard practice to over estimate the amount of RhIG to be administered to ensure coverage of the exposure. The calculated dose is rounded to the nearest full dose and an additional dose is added to ensure that Rh sensitization does not occur. The standard dose of RhIG (300g) covers an exposure of 15 mL of D positive fetal red cells (30 mL whole blood). The formula to calculate the RhIG dose to be given depends on whether the exposure is quantitated as a volume of whole blood or red cells. Usually, whole blood volume is used in the calculations. e.g.: For this 63.7 mL fetal bleed, 63.7/30 = 2.1 the mother should get a total of 3 doses (3 300 g vials) ( 2.1 rounded* to 2 doses; add 1 dose = 3 doses total ) For an 80 mL fetal bleed, 80/30 = 2.7 thus, 4 doses are needed. ( 2.7 rounded** to 3 doses; add 1 dose = 4 doses total ) If red cell volume is desired for any reason, multiply the maternal blood volume by her hematocrit/100. Then, use 15 mL as the fetal red cells volume that is neutralized by the 300 g dose of RhIG. Rounding Rules: Always add 1 vial (dose) to the “rounded” number of vials (doses). *a. If decimal is 0.1 - 0.4, stop (round down); then add 1 **b. If decimal is 0.5 - 0.9, add 1 (round up); then add 1 STAT Hemoglobin S: The routine method for quantitation of HbS is by HPLC in special hematology. This is run during the day: Monday, Wednesday, and Friday. HbS measurements are sometimes needed on an emergent basis, usually when there is a question of whether to do an exchange transfusion; if the patient has not been recently transfused or exchanged recently, then %S should be at baseline and quantitation is unlikely to be helpful. There is really no other good reason to order a STAT HbS level. Many times it is ordered STAT by mistake and the clinician can wait for the routine HPLC method. There used to be a column HbS method which the manufacturer stopped supporting so is not run anymore. Orders for this should be directed to HPLC instead. Review of Peripheral smears: Technologists may call to tell you they have an abnormal finding in a smear. If you are still in house, you should go and look at the smear. You should discuss the findings with the technologist and your attending if necessary. It is your job is to find out the clinical story by contacting the physician who sent the smear and let them know your findings. Manual differential/Band count: Manual differentials are performed for selected criteria by the hematology lab. These criteria are based on the white count, automated differential results (and flags by computer), and comparison with previous results. You may be called by a clinician who feels a manual differential is indicated for their patient. You should find out the indication for the manual differential and explain to them the difference between a manual (100 cells, labor intensive) and automated differential (thousands of cells, not good at low WBC <1.5). See Pierre RV. Peripheral blood film review. The demise of the eyecount leukocyte differential. Clin Lab Med. 2002 Mar;22(1):279-97. Pdf version is available on the Intranet http://info.med.yale.edu/labmed/intranet/files/oncall/Manual/ A one time band count is appropriate only as part of a sepsis work-up in patients less than 3 months of age. See Cornbleet PJ. Clinical utility of the band count. Clin Lab Med. 2002 Mar;22(1):101-36. Pdf version is available on the Intranet http://info.med.yale.edu/labmed/intranet/files/oncall/Manual/ In neutropenic patients (<1.5), manual differentials are done Monday, Wednesday, and Friday. The clinicians may not be aware of this and sometimes if they call on a Tuesday and you tell them this, they will be happy with that. It is helpful in borderline cases to tell the clinician that you will check out the automated differential and see if there were any flags and then discuss it further with them. Lastly, sometimes the clinician may feel there could be “something wrong” with the automated differential (i.e. it doesn’t match previous diff or previous history) and then a manual differential can be done to check it. Manual differentials can only be performed on a recent (collected in the last 4 hours specimen) since the WBC will degenerate. D-Dimer The Hematology Lab offers two different D-Dimer assays: D-Dimer and D-Dimer (Thrombosis). The standard D-Dimer test is for DIC. The D-Dimer (Thrombosis) is for ruling out PE in patients with low probability for PE in the ED. The regular D-Dimer should not be used for rule out PE and the D-Dimer (Thrombosis) should not be used for inpatients. It is okay to approve the D-Dimer (Thrombosis) for an outpatient if there is low probability for PE (based on clinical assessment such as Wells criteria). Microbiology Gram stain Microbiology is open until 12 midnight and will do gram stains up until then. However, there are rare occasions when a gram stain is requested after midnight and before 6 am when Micro re-opens. Hematology technologists can usually see bacteria on a Wright stain and gram stains can be performed by the hematology technologists if it is indicated. Your job is to find out the indications and if it is needed before microbiology re-opens. See e-mail from Dr. Edberg below Date: Wed, 13 Apr 2005 18:11:31 -0400 From: John M Fisk <john.fisk@yale.edu> To: “Bennett, Jonathan” <jonathan.bennett@yale.edu>, “Fisk, John” <john.fisk@yale.edu>, “Eid, Tore” <tore.eid@yale.edu>, “McCalip, Benjamin” <benjamin.mccalip@yale.edu>, “Genzen, Jonathan” <jonathan.genzen@yale.edu>, “Tzou, Abraham” <abraham.tzou@yale.edu>, “Tian, Shulan “ <shulan.tian@yale.edu>, “Oethinger, Margret D.” <margret.oethinger@yale.edu>, “Tormey, Christopher” <christopher.tormey@yale.edu>, “Pelletier, Joseph P.” <joseph.pelletier@yale.edu>, “Transue, Sarah “ <sarah.transue@yale.edu>, “Browne, Frederick A “ <frederick.browne@yale.edu>, “Torres, Richard “ <richard.torres@yale.edu>, “Klein, Roger “ <roger.klein@yale.edu>, “Ripps, Michael E., M.D., Ph.D.” <mripps@vzw.blackberry.net> Cc: “Rinder, Henry M.” <henry.rinder@yale.edu>, “Edberg, Stephen “ <stephen.edberg@yale.edu> Subject: [Fwd: Re: Gram Stains] Another page in your on-call notebook... Hi folks, Recently, Ed Sullivan (the Hematology Lab Manager) asked for help regarding the apparent increase in “off-hours” requests for gram stains. In the past couple weeks, there have been requests for gram stains -- sometimes on tissue specimens, and on at least one occasion in which the initial Wright-Giemsa stain was negative -- and the approval for gram staining under these circumstances has been called into question. In order to ensure that these cases are handled appropriately (especially at 2 AM when most of us loathe the notion of having to call an attending), I posed the question to Drs. Edberg & Bia with a request for guidance. The salient issues include: 1) should gram stains be performed on specimens for which a Wright-Giemsa stain has already been performed? 2) is it advisable to open a “sterile” specimen container in order to perform a gram stain, and thereby potentially contaminate it? 3) should the hematology lab handle non-fluid specimens (such as soft tissue specimens)? Dr. Edberg addresses all of these issues in his email below. Please read it carefully and make sure that you clearly understand the issues and feel comfortable with how to handle these requests. For those of us with “2 AM syndrome”, it might not hurt to print this and stick it in your on-call notebook in case you need a quick refresher in the wee hours of the morning. The only other thing to add to his note is that the on-call resident probably ought to: 1) call the Micro Lab once there is a reasonable certainty of there being someone there and willing to pick up the phone (probably by 6:30 AM), and let them know if there is a specimen that needs urgent attention 2) as always, sign the case out to the Micro resident and/or the fellow thanks! John -------- Original Message -------- Subject: Re: Gram Stains Date: Tue, 12 Apr 2005 14:47:56 -0400 From: Stephen Edberg <Stephen.Edberg@yale.edu> To: John M Fisk <john.fisk@yale.edu>, “Bia, Frank” <frank.bia@yale.edu> CC: Edmund Sullivan <Edmund.Sullivan@ynhh.org>, “McPhedran, Peter “ <peter.mcphedran@yale.edu>, “Rinder, Henry M.” <henry.rinder@yale.edu> References: <s25aa5ad.065@mercury.mis.ynhh.com> <425BDC6E.7060707@yale.edu> John, The WG stain will detect bacteria and fungi with at least the same sensitivity as the gram stain (and could actually be better). Hematology uses the cytofuge to prepare the smear (assuming CSF or urine), which is the most sensitive method. Therefore, for the detection of bacteria and fungi, this is sufficient. When reporting the WG stain it is imperative, especially when speaking on the phone to someone, to be absolutely clear that the WG stain does not differentiate Gram positives from negatives. Therefore, if the WG stain is negative for bacteria and fungi, there is no point in doing a Gram stain. If the WG stain is positive (and note, be careful how that word is used. We once had a resident report “I’m positive there are cocci” which was taken by the listener as “positive cocci”, and they weren’t) what to do? First, it is a clinical decision. If the results of the gram stain will modify therapy, I believe it should be done. The resident can ask this question. For example, if cocci are seen in the CSF in a primary meningitis, ceftriaxone will be used for all microbial candidates (unless there is something odd in the history). Unless special circumstances, a Gram stain is not necessary. If positive rods, Listeria must be entertained. The resident should be able to ascertain the answer to this question. Second, all the Hematology technologists are ASCP, and can do a gram stain. It is particularly important to perform a control on the slide, since they may not do them frequently. The best control is a swab of the inner mouth. The gram stain can be done from the Hematology specimen, or from the Chemistry specimen, so there should be no contamination issue. If the Micro specimen must be used in a particular case, a sterile 0.01 urine loop and gloves will keep it “sterile enough”, since we are not looking for skin contaminants (except from patients with shunts). Some hospitals, and all commercial labs, have generalists at night. We used to have a night technologist but he was removed in a budget cut. I think we should have generalists at night for issues like this and general efficiency, and for the blood culture machine. Just a management note for the residents. Regarding tissue specimens: these need be emulsified in a sterile mortar/pestle apparatus, so Hematology really can’t do this. Lastly, we arranged Micro’s schedule so that someone arrives at 6 a.m. SCE At 10:34 AM 4/12/2005, John M Fisk wrote: > Under what circumstances should a specimen be left until it can be > processed in Micro? > > Under what circumstatnces should a gram stain be performed, even if > it means potentially contaminating the specimen in the process? > > Are there circumstances in which a WG stain would NOT pick up an > organism that a gram stain would? (with the obvious proviso that a WG > stain cannot allow differentiation of gram positive vs gram negative) > > > 3) tissue specimens have been received with a request for a gram > stain: the Hematology lab is simply not set up to perform gram stains > on these types of specimens. -- John M Fisk, M.D. Administrative Chief Resident, Department of Laboratory Medicine Yale University School of Medicine, New Haven, CT pager: (860) 588-8971 phone: (203) 737-2088 Immunology Immunology is not open in the evenings or on the weekends. You can get the key for the laboratory in Flow Cytometry if you need reports that are filed in Immunology (IFE, Factor V Leiden, Prothrombin, MTHFR, lymphocyte proliferation, colony stimulation assays) or to access the card file that has all the send out tests for Immunology. If you have questions regarding immunology tests that you cannot answer, you can call the attending on Immunology and we also a “weekend” pager worn by the manager of Immunology, Josephine. Actually, Josephine asks that you call her at home first 203-284-9924 and then if no answer try the beeper 412-0838. Viscosity/IgA There occasional requests for viscosity or IgA testing on weekends. If the viscosity would be used to determine therapy (e.g. plasmapheresis in multiple myeloma), then it should be arranged. If you get a request for an IgA level before giving IVIG, this is not typically needed before the first dose of IVIG; even if the patient was IgA deficient, anti-IgA should not be an issue without prior exposure. Virology There are very few calls for virology and nothing of any recurrent nature except for the occasional request for HIV testing in the middle of the night for patients in labor and delivery. Make sure you are familiar with the protocols for liver transplant (notifying virology), needlestick and rapid HIV test requests, SARS guidelines, and others provided by Dr. Landry. In general, the hours of virology are 7-7 M-F and 8-3 Sat. In flu season, the hours may be later into the night, but usually not past 10-12pm. VA You will be called by VA clinicians to approve all blood product orders except RBC’s. Transfusion audit criteria are included below: Other miscellaneous calls from the VA can be handled very similarly to calls at Yale. Requests for myobacterial blood cultures: green top tube. (At Yale it’s a light blue top/citrate) Chemistry Critical Values: In the Emergency Department, these are usually Toxicology cases and Dr Hodsdon’s handout should provide all the necessary background information necessary. Read the section pertaining to the issue you are called about prior to calling the ER, this will help you to assist the clinicians if necessary. The chemistry technologist will call you with the result. Get all information you can from the technologist including the test results, when the specimens were drawn, and will there be any other confirmatory tests done. Ask if there were other negative toxicology results as well. Usually the actual results have already been reported to the ER by the technologist, but you should have an MD to MD conversation. Tell the clinician the result and say you wanted to make sure he/she was aware of it. Then say you are interested in following up the results and would like to obtain some clinical history. Also offer any assistance in interpreting the results (i.e. esp TCA results) or further laboratory work-up. If there will be follow-up or confirmatory tests done automatically by the lab, let the clinician know. You can remind them there is a clinical toxicologist (641-Toxi, Dr. Carl Baum; Dr. Asim Tarabar another option) available if they need a consultation for unusual cases. Questions for patients outside YNHH should be referred to Poison Control (1-800-222-1222). Other critical values may be reported to you from any lab. These are usually in situations where the laboratory cannot reach the ordering physician. Critical values must be report by law. You basically have to chase someone down to report the results to. Most clinics and doctor’s offices have someone on call (the page operator can help x83111) and it is sufficient to report the results to an on-call person. Get the name of the person to whom you reported the results and give that name to the lab to enter into the computer. Also, if possible, obtain a clinical history. Off hours drug levels: Requests for off hours drug levels can be handled by getting the clinical indications for the test from the clinician. Then speak with Chemistry and find out the usual schedule for the test. If the clinician can wait for the usual run, that if fine. However, if they need an emergent drug level and there is mutual feeling that it is indicated, then speak with chemistry to see it there is sufficient technical staff/expertise to do the test. If any test in chemistry is truly indicated, a technologist can be called in. You should consult the attending in these cases. Urine Drugs of Abuse testing: Dr Hodsdon has provided another handout on the urine drugs of abuse panel which is very helpful. Occasionally, you will have to help someone interpret results of these screens. Dr. Hodsdon’s pdfs are available on the Lab Medicine Web site http://info.med.yale.edu/labmed/protected/lectures.html username = resident, password = path0l0gy Pheochromocytoma/Neuroblastoma Many tests exist for pheochromocytoma (urine/plasma, 24 h/spot, catecholamines/metaphrines/VMA). Based on institutional practice (Dr. Donabedian), the standard work-up for pheochromocytoma at YNHH is a 24 hour urine for catecholamines and VMA. Other options we send out to Mayo include plasma free metanephrines (touted as single best test for screening in a 2002 JAMA article; may be more sensitive but less specific) and 24 hour urine metanephrines. Dr. Donabedian would not approve of plasma catecholamines to be sent out. For neuroblastoma, urine should be tested for catecholamines and HVA. 24 hour urine is not required for pediatric patients. Porphyria It is typically sufficient to know that 24 hour urine for porphobilinogen should be ordered for acute intermittent porphyria (neurovisceral symptoms) and that 24 hour urine for porphyrins should be ordered for porphyria cutanea tarda (photosensitivity). The elevations in different metabolites reflect different blocks in the pathway. For details on the metabolic pathway and other types of porphyria, check a reference source. 1