February 20, 2008 Katerina Pavenski, MD FRCPC (Hematology) Transfusion Medicine Fellow, McMaster University Special thanks to Drs. J. Callum, J. Pendergrast and Y. Lin for their assistance with this presentation 1 Introduction to blood products Red blood cells Frozen plasma Cryoprecipitate Platelets When to transfuse? How to order? What are the major risks? 2 56 year old man post-op day 2 from esophagectomy for esophageal carcinoma No history of cardiac disease Not currently bleeding Vital signs HR 90, BP 140/80 Laboratory investigations Hgb 80 g/L 3 The total volume of a unit of RBC is ~280 mL: 160 mL of red cells 60 mL of plasma 60 mL of anticoagulant (CPD) and preservative (Saline Adenine Glucose Mannitol) SAGM (60 ml) O Must be ABO compatible with the recipient 4 Recipient Donor A A, O B B, O AB AB, A, B, O O O 5 1.Transfusion MIGHT occur during admission 2. Surgery planned with <10% risk of transfusion 1. Transfusion PLANNED 2. Surgery with at least 10% risk of transfusion Group & Screen Group & Screen & Cross-match Group ABO Group, Rh Group Screen Antibody Screen Cross-match Anti-globulin cross-match, immediate spin or electronic cross-match 6 Inform patient of material risks of transfusion At minimum: risk of viral and bacterial infection, transfusionrelated acute lung injury, acute hemolysis, common minor reactions (fever, urticaria) Inform patient of benefits and possible alternatives Document in chart that informed consent has been obtained Informed consent must be completed by a physician Informed consent is mandatory in all cases except where: Patient’s life is at immediate risk, AND Neither patient nor surrogate decision-maker are able to provide consent 7 A unit of RBC is expected to raise hemoglobin by 10 g/L Transfuse a single unit over 2 hours but not more than 4 hours RBCs are stored at 1-6ºC Consider using a blood warmer if transfusing many units Blood is compatible only with saline 8 Pre-medication is not necessary consider furosemide for patients with suspected impaired cardiac function Assess the outcome of transfusion (clinical, hemoglobin level) before transfusing further 9 Order 1 unit at a time, reassess patient and Hgb between units Jan 1st, 2008 @ 09:00h Max is 4 hours per unit Transfuse 1 unit of RBC over 2 hours for Hb 65 and tachycardia. I. Transfusalot, MD Always include indication for transfusion 10 RBC Product Turn-Around Time Comments Uncrossmatched blood 5 minutes Only in emergencies (when risks of delaying transfusion outweigh risks of acute hemolysis) Group-specific, uncrossmatched RBCs 10 minutes As above; matching for ABO and RhD preserves O-Neg stock Crossmatched RBCs 45 minutes for patients without antibodies, up to 3 hours for patients with antibodies Preferred choice, as safest product available 11 56 year old man post-op day 2 from esophagectomy for esophageal carcinoma No history of cardiac disease Not currently bleeding Vital signs: HR 90, BP 140/80 Labs: Hgb 80 g/L Would this patient benefit from RBC transfusion? Current evidence indicates that a transfusion should not be given at this time… 12 0 g/L 70 g/L 80 g/L 90 g/L Why not transfuse? 100 g/L 140 g/L Why transfuse? Decreasing Decreasing benefit benefit 13 Maintain hemoglobin >70 g/L during active bleeding1 Consider rate of bleeding, hemodynamic factors, and evidence of tissue ischemia Post-transfusion Hgb > 100 g/L should be avoided Consider maintaining a higher hemoglobin level (85-100 g/L) for patients with2: Impaired pulmonary function Increased oxygen consumption (fever, chills) Atherosclerosis Unstable coronary syndromes 1. 2. British Committee for Standards in Haematology, Blood Transfusion Task Force. British Journal of Haematology 2001; 113: 24-31 Clinical practice guidelines. Appropriate use of red blood cells. National Health and Medical Research Council, Canberra, Australia 2001 14 In a non-bleeding critical care patient, keeping Hgb > 100 g/L is not indicated In most patients, maintaining Hgb > 70 g/L is adequate In patients with symptomatic anemia, consider maintaining a higher hemoglobin level Confusion, pre-syncope, tachycardia/arhythmia, angina, tachypnea, heart failure, tissue ischemia 15 Hebert et al. A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. NEJM 1999; 340: 409-417 838 ICU patients randomized to two different transfusion strategies Restrictive: transfuse only if Hgb < 70 g/L Liberal: transfuse only if Hgb < 100 g/L Outcomes: No difference in 30 d mortality (18.7 vs 23.3%) No difference in overall mortality for patients with history of ischemic heart disease (20.5 vs. 22.9%) Reduced in-hospital mortality (22.2 vs. 28.1%) 16 Subgroup analysis suggests restrictive strategy of greatest benefit in younger patients and those with lower APACHE II scores 17 Cause of higher mortality with liberal transfusion strategy unclear; may be related to increased risk of myocardial infarction, pulmonary edema and ARDS 18 56 year old man post-op day 2 from esophagectomy for esophageal carcinoma No history of cardiac disease Not currently bleeding Vital signs: HR 90, BP 140/80 Labs: Hgb 80 g/L ECG shows evidence of acute ischemia Now would this patient benefit from an RBC transfusion? Current evidence does not provide a clear answer to guide use of RBC transfusion in setting of ischemia… 19 • Conflicting evidence from three retrospective studies… • Recommend transfusion • if Hgb < 80 if symptoms have resolved, OR • Hgb < 100 g/L if ongoing ischemia Publication Result Wu et al. NEJM 2001;345:1230-6 Transfusion decreases mortality in patients with Hct < 33% (OR 0.22-0.69) Rao et al. JAMA 2004;292;1555-62 Transfusion increases mortality in patients with Hct > 25% (OR 3.94) Yang et al. J Am Coll Cardiol 2005;1490-5 Transfusion increases mortality, with baseline Hct of 26% in transfused patients vs 35% in non-transfused patients (adjusted OR 1.67) 20 56 year old man post-op day 2 from esophagectomy for esophageal carcinoma No history of cardiac disease Not currently bleeding HR 90, BP 140/80 New labs: Hgb is now 60 g/L When you approach the patient to obtain informed consent, he refuses to sign stating religious objections, as a Jehovah’s Witness, to blood transfusion… 21 Risk of mortality proportional to severity of anemia1 Mortality (%) 100 90 80 70 60 50 40 30 20 10 0 non-cardiac cardiac 71-80 61-70 51-60 41-50 31-40 21-30 11-20 Hgb (g/L) 1. Carson J, et al. Transfusion 2002;42:812-818 22 Suggested management: 1. Minimize phlebotomies for laboratory tests 2. Be vigilant for other causes of anemia 3. Provide adequate nutritional support a) Ferrous fumarate 300 mg po BID b) Folic acid 5 mg po OD c) Vitamin B12 1 mg po OD 4. Start erythropoietin 20 000 IU SQ OD1 if a) Hgb < 100 g/L b) Hgb < 120 g/L and surgery anticipated Discontinue Epo once target Hgb achieved 5. In setting of ongoing blood loss, judicious use of hemostatic agents (antifibrinolytics and/or rVIIa) 1. Corwin HL, et al. Crit Care Med 1999;27:2346-50 64 year-old woman on warfarin for stroke prevention in setting of atrial fibrillation, admitted to ICU with severe pneumonia, requires immediate central line placement INR therapeutic at 2.8 What do you need to know before ordering FP for this patient? 23 24 Types of plasma Frozen plasma (FP) - whole-blood derived, volume of 1 unit is ~250 mL Apheresis plasma – collected by apheresis, volume of 1 unit is ~500 mL Contains all necessary clotting factors for hemostasis, each with different halflife Overall half-life of FP in non-bleeding patient is 6-8 hours Must be ABO compatible with recipient AB 25 Recipient Donor A A, AB B B, AB AB AB O O, A, B, AB 26 A dose of 10-20 mL/kg of FP will increase all coagulation factors by ~30%, which is usually adequate for hemostasis and will reduce INR to < 1.5 Small adult: 3 units Large adult: 4 units Providing smaller doses will be ineffective1 Plasma is stored in a frozen state (-18C or lower) Thawing takes ~30 min 1. Dara SI et al. Crit Care Med 2005;33:2667-71 27 Only compatible with normal saline Transfuse each unit over 30-120 minutes (maximum 4 hours) Assess the outcome (clinical, INR and aPTT) following transfusion 28 Cardiac surgery Casbard et al. The role of prophylactic FFP in reducing blood loss and correcting coagulopathy in cardiac surgery: a systematic review. Anaesthesia 2004; 59: 550-558. Prophylactic FP vs. no FP (or non-plasma alternative) post CPB No effect on blood loss or transfusion requirements 29 Intensive care Dara et al. FFP transfusion in critically ill medical patients with coagulopathy. Crit Care Med 2005, 33: 2667-2671 Single centre, retrospective cohort in MICU Patients with INR>1.5 who received FP (vs. who did not) had similar rate of bleeding and higher incidence of acute lung injury 30 Liver disease1 Correction of elevated INR requires large volumes of FP Effects of transfusion are short-lived No association between elevated INR and bleeding Decreased production of procoagulants is balanced by decreased production in anticoagulants 1. Stanworth 2007 31 Massive transfusion No good quality evidence Guidelines: ATLS, ASA, CAP, ABC-T (keep INR<1.5) New studies Johansson et al 2007. Proactive administration of platelets and plasma for patients with a ruptured AAA: evaluating a change in transfusion practice. Gonzales et al 2007. FFP should be given earlier to patients requiring massive transfusion. Borgman et al 2007.The ratio of blood products transfused affects mortality in patients receiving massive transfusions at a combat support hospital. 32 64 year-old woman on warfarin for stroke prevention in setting of atrial fibrillation, admitted to ICU with severe pneumonia Patient has received 3 units of FP, and central line placed successfully. Bronchoscopy with biopsy planned for following day INR 1.5 immediately following plasma infusion Does this patient require any additional management prior to bronchoscopy? Yes! Effect of FP will be lost by the following day. Effects of warfarin will likely still be present, requiring additional treatment with Vitamin K 33 Vitamin K Corrects coagulopathy due to vitamin K deficiency (eg., malnutrition, therapy with warfarin) Most patients will have substantial reduction in INR within 6-12 hours of receiving IV vitamin K Oral vitamin K may take 12-24 hours Vitamin K should not be administered IM (increases risk of hematoma) or SC (less effective than oral or IV forms) 34 Condition Recommendation INR <5 Hold warfarin and adjust dose INR 5-9 Hold warfarin and give vitamin K 1-2.5 mg po INR >9 Hold warfarin and give vitamin K 5-10 mg po INR > 1.5 and major bleeding Hold warfarin, give vitamin K 10 mg IV and 3-4 units of FP INR > 1.5 and major procedure planned Hold warfarin, give vitamin K 10 mg IV • if procedure not planned within 6 hours, repeat INR 1 hour prior to procedure to confirm INR < 1.5 • if procedure must be performed (for medical reasons) within 6 hours, also give 3-4 units of FP in addition to vitamin K Adapted from Ansell J et al, Chest 2004;126:204S-33S 64 year-old woman on warfarin for stroke prevention in setting of atrial fibrillation, admitted to ICU with severe pneumonia Patient’s condition deteriorates, develops sepsis and disseminated intravascular coagulation, diffuse microvascular bleeding noted from IV sites and endotracheal tube STAT blood tests reveal platelet count 40 x 109/L, INR 3.5, aPTT 76, Fibrinogen 0.6 g/L Patient ordered 4 units of FP and 5 units of platelets. What other blood product should this patient receive? This patient should receive cryoprecipitate… 35 36 The volume of a unit of cryoprecipitate is ~15 mL, and contains high concentrations of FVIII (80 IU), vWF and fibrinogen Used primarily for fibrinogen replacement, with each unit containing ~150 mg of fibrinogen Adult dose is 1 unit per 5-10 kg of body weight Small adult: 8 units Large adult: 12 units One adult dose will increase plasma fibrinogen level by ~1 g/L (0.60-1.0 g/L) 37 Cryoprecipitate is stored at -18C or colder Thawing and pooling requires ~30 min Transfuse each dose of cryoprecipitate over 10-30 minutes (maximum 4 hours) Assess the outcome (clinical, fibrinogen) following transfusion 38 Documented hypofibrinogenemia (<1.0 g/L) and bleeding Inherited hypofibrinogenemia or dysfibrinogenemia Acquired hypofibrinogenemia DIC, post-thrombolytic therapy, liver disease Massive transfusion Cryoprecipitate may be requested prior to laboratory results being available in cases suggestive of a low fibrinogen concentration, including: Disseminated intravascular coagulation Following massive transfusion (eg., > 10 units of RBCs in 24 hours) Not recommended for treatment of von Willebrand’s disease or hemophilia (FVIII deficiency) 39 30 year-old man undergoing induction chemotherapy for acute myeloid leukemia admitted to ICU with febrile neutropenia and septic shock Lab results reveal platelet count 15 x 109/L. No evidence of bleeding Your attending physician asks you to “give the patient some platelets” 40 Types of platelet products: 1. Buffy coat platelets – whole-blood derived, pool of 4 group-matched platelet concentrates suspended in plasma of a male donor (one of the 4) total volume ~300 mL/pool 2. Single donor platelets – collected by apheresis, platelet concentrate and plasma from a single donor, total volume ~300 ml/unit Order “one adult platelet dose” 1 buffy coat platelet pool OR 1 single donor platelet concentrate 1 adult dose will increase platelet count at 1 hour by 40 x 109/L 41 Transfuse each dose over 60 minutes (maximum 4 hours) Platelets only compatible with normal saline ABO identical platelets are preferred but not essential Platelets are stored at RT Wait time for platelets is 5-10 minutes Assess the outcome (clinical, platelet count) following transfusion 42 PLT <10 CONDITION Immune thrombocytopenia <10 Non-immune thrombocytopenia (e.g. bone marrow failure) <20 Non-immune thrombocytopenia with fever > 38.5ºC or coagulopathy <20 Procedures not associated with significant blood loss 20-50 Procedures not associated with significant blood loss Transfuse 1 dose 1 dose of platelets on hold, transfuse only if serious bleeding Transfuse 1 dose immediately before procedure Transfuse 1 dose immediately before procedure Transfuse 1 dose Lumbar puncture <50 Massive bleeding or procedures not associated with significant blood loss Peri-neurosurgery or head trauma Platelet dysfunction and marked Transfuse 1 dose bleeding (e.g. post cardiopulmonary bypass, aspirin, antiplatelet agents) Any Transfuse 1 dose <50 <100 RECOMMENDATION Transfuse only with serious bleeding Transfuse 1 dose 43 Try to determine the cause of thrombocytopenia before transfusing platelets For some causes, platelet transfusion is relatively contraindicated Heparin-induced thrombocytopenia (HIT) Thrombotic thrombocytopenic purpura (TTP) In the above conditions, platelet transfusion should only be considered in the setting of serious bleeding 44 If the platelet count doesn’t increase significantly 1 hour after a platelet transfusion, your patient may be refractory Follow algorithm to determine etiology and manage 45 58 year-old man admitted to CVICU following urgent aortocoronary bypass graft surgery Patient had been on ASA and clopidogrel pre-operatively and had prolonged time on pump On arrival to ICU, patient bleeding heavily from chest tubes, initial laboratory results reveal Platelets 120 x 109/L aPTT 38 seconds, and INR 1.4 Fibrinogen 2.2 g/L 46 Is the bleeding excessive? > 300 ml in first hour, > 250 mL in 2nd hour, or > 150 mL/hr thereafter1 Is there a coagulopathy? Ensure heparin has been fully reversed (1 mg protamine/100 units of heparin) Use FP and/or cryo to keep aPTT < 45 sec, INR < 1.5 and fibrinogen > 1.0 g/L Has maximum dose of antifibrinolytics been administered? If aprotinin: max total dose = 6 mU If tranexamic acid: max dose = 100 mg/kg 1. Michelson EL, et al. Am J Surg 1980;139:313-7 47 Have platelets been transfused since patient taken off bypass pump? Platelet dysfunction is common post-bypass If excessive bleeding continues despite adequate doses of protamine, antifibrinolytics and correction of coagulopathy, transfuse 1 dose of platelets regardless of platelet count; then consider a 2nd dose of platelets if ongoing bleeding Has a surgical cause of bleeding been excluded? If at this point excessive bleeding continues, patient may require surgical re-exploration Would this patient benefit from rVIIa? If all other measures have failed to control bleeding, consult hematologist on call re: further management including rVIIa48 32 year old G3P3 with severe post-partum hemorrhage, admitted to ICU Bleeding controlled, Hgb now 55 g/L She and her husband are very worried about having a blood transfusion They want to know the risks… Here’s what you need to know about the risks of blood transfusion… 49 You inform the patient that all blood donations are tested for: HIV Hepatitis B and C Human T-cell Lymphotropic Virus (HTLV) Bacterial contamination (platelets only) Syphilis West Nile Virus However, there are residual risks… 50 Residual risk for all donors per million donations (95% CI) Virus HIV 0.13 (0.05-0.28) 1 in 7.8 million HCV 0.43 (0.27-0.66) 1 in 2.3 million HBV 6.55 (3.90-10.29) 1 in 153 thousand 0.23 (0.04-0.83) 1 in 4.3 million unknown unknown WNV O'Brien 2007 Component Incidence of bacterial contamination Incidence of symptomatic septic reaction 51 Incidence of fatal bacterial sepsis Platelet concentrate pool 1 in 1,000 1 in 10,000 1 in 40,000 Packed red blood cells (1 unit) 1 in 50,000 1 in 100,000 1 in 500,000 Clinical Guide to Transfusion. CBS 2007 52 53 1. Acute hemolysis 2. Sepsis 3. Transfusion-associated acute lung injury (TRALI) 4. Transfusion-associated circulatory overload (TACO) 5. Anaphylaxis 54 1. Always obtain informed consent before transfusing • 2. Transfusion should only be prescribed when benefits outweigh risks Don’t transfuse RBCs unless patient has symptomatic anemia or Hgb < 70 g/L • Give one unit at a time 3. Don’t transfuse platelets prophylactically unless platelet count < 10, or < 50 and patient scheduled for surgery 4. Don’t transfuse FP to correct an INR > 1.5 if vitamin K will do 5. If patient is bleeding and fibrinogen < 1.0 g/L, cryoprecipitate is the preferred blood product 6. If in doubt, ask for help (call the blood bank) 55