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22/March/2010 Mazin Jan, MD, FRCPC

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1 22/March/2010 Mazin Jan, MD, FRCPC
Transfusion Medicine 22/March/2010 Mazin Jan, MD, FRCPC

2 Transfusion Medicine Basics

3 Transfusion: Risks and Informed Consent
Physicians ordering transfusion must have current knowledge of the risks of and alternatives to red blood cell and plasma transfusion. Patients should be informed of the possibility of transfusion and informed of benefits, risks, and available alternatives, far enough in advance of planned medical or surgical interventions. Patients should be informed that they have received a transfusion

4 The Regulator vs. The Blood Collection Agencies
Health Canada enforces strict standards for screening donors for collection, processing and distribution of blood and components Canadian Blood Services (CBS) and Hema-Quebec are responsible for donor recruitment collection, processing and distribution of blood components Supply of manufactured products (e.g. albumin, clotting factor VIII)

5 Autologous and Directed Donation
Autologous blood (patient’s own blood) may be collected in advance of elective surgery by CBS or at the treating hospital Directed donations from parent to minor child, from selected donors for patients with rare blood types or platelet refractor-iness are available through CBS

6 Donor Screening Each donation is accompanied by a Record of Donation, consisting of two parts: Questions about e.g. general health, travel Questions by a skilled interviewer about “risk behaviors” e.g. illicit drug use

7 Testing the Donation I. Red cell type Antibodies present
Recipient Compatibility Approximate frequency Group O (no ABO antigens) Anti-A, anti-B All ABO groups 46% Group A Anti-B Groups A & AB 42% Group B Anti-A Groups B & AB 9% Group AB Neither present 3% Rhesus group D positive Normally none Should be RhD identical, RhD –ve acceptable 85% Rhesus group D negative Should be RhD identical 15%

8 Testing the Donation II.
All donations are tested for some infectious agents: HIV by antibody and NAT HCV by antibody and NAT HBV by antibody WNV by NAT Syphilis by antibody Some donations are tested for cytomegalovirus (CMV) and so labeled

9 Removal of White Cells (Leukoreduction)
Leukoreduction: All blood donations have the white cells removed (>99.99%) Provide no benefit Predispose to febrile reactions and platelet refractoriness Harbor organisms (e.g. CMV, HTLV) Theoretical risk of abnormal prion transmission is reduced Theoretical risk of immuno- suppression is reduced

10 Making Components Donation of 450mL blood in 60mL anticoagulant yields: 160mL red cells in total of 280mL, including added nutrient About 250mL frozen plasma 5.5x1010 platelets in 70mL Cryoprecipitate (fibrinogen, factor VIII, von Willebrand factor) in 15mL

11 Components – Shelf-life, Storage & Compatibility
Compatibility requirements Red blood cells 42 days (35 for autologous) 1-6o C ABO, RhD compatible, identical if possible Platelets (random donor) 5 days 20-24o C with constant mixing ABO RhD identical if possible; blood group barriers may Platelets (single donor apheresis) be crossed. Anti-D prophylaxis required for some recipients Frozen plasma 12 months Minus 18o C or lower ABO compatible preferred Cryoprecipitate

12 Importance of Patient Identification to Safe Transfusion Practice
The root cause of most major blood group incompatible reactions is failure to identify the patient: when taking the specimen for cross-match when hanging the red cell bag. Accurate and careful identity checks are required: At specimen procurement At each stage of handling in the laboratory At the place of transfusion before starting the transfusion

13 When to Order “Group & Screen” and When to Consider Cross-match
1.Transfusion MIGHT occur during admission 2. Surgery planned with <10% risk of transfusion 1. Transfusion PLANNED 2. Surgery with at least a 10% risk of transfusion Group & Screen Group & Screen & Cross-match Group ABO Group, Rh Group Screen Antibody Screen Cross-match Anti-globulin cross-match, or abbreviated cross-match

14 Red Blood Cell Transfusion
This section covers: Contents of a unit of red cells Patient testing Selection of compatible units Expected outcome of transfusion Good transfusion practices Guidelines for use of red cells

15 Red Blood Cells for Transfusion
A unit of red cells contains 280mL, made up of 160mL of red cells 60mL of plasma 60mL of anticoagulant (citrate) and preservative

16 Selecting Compatible Red Cells I.
Identical ABO and RhD type preferred Red cells of non-identical ABO type may be used as displayed above: Group O cells may be given for all other ABO types AB cells can only be given to AB patients

17 Selecting Compatible Red Cells II.
The RhD antigen is highly immunogenic Transfusing RhD +ve blood to an RhD -ve patient should be avoided wherever possible RhD –ve females with child-bearing potential should never receive any RhD +ve products unless there is no alternative Such female RhD –ve patients should receive prophylactic treatment with anti-D Patients with an unexpected antibody should receive only red cells lacking the corresponding blood group antigen

18 Transfusion of Red Cells
RBCs must be transfused through a blood administration filter ( microns) A unit of red cells is expected to raise the hemoglobin 10 g/L Transfuse a single unit over 2 hours and not more than 4 hours if no massive bleeding Assess the outcome (clinical, hemoglobin level) before transfusing further

19 Transfusion of Red Cells
Start within 30 minutes of removing RBCs from refrigeration RBCs are compatible ONLY with normal saline Freezing or heating blood may cause hemolysis, and may harm the patient Check patient’s VS; Transfuse slowly (50 mL/hr) for thefirst 15 minutes Monitor the patient closely for the first 15 minutes.

20 Transfusion in Acute Blood Loss
Maintain hemoglobin over 70 g/L during active bleeding Anticipate need when hemoglobin drops below 80 g/L Consider maintaining higher level ( g/L) with: Impaired pulmonary function Increased oxygen consumption (e.g. fever) Unstable coronary disease Atherosclerosis Uncontrolled bleeding Patients with levels above 100 g/L are unlikely to benefit

21 Transfusion in the Critically Ill
No general benefit (& possible harm) until hemoglobin falls to 70 g/L Transfusion recommended below 70 g/L Consider higher levels (100 g/L) in patients with unstable angina or acute M I Consider transfusing if there are clear signs of inadequate tissue oxygen delivery

22 Transfusion and the Peri-operative Patient
Pre-operatively, consider alternatives in advance (at least 5 weeks) of surgery to allow planning: . Iron, Folic aid, B12, Erythropoietin, Autologus donation. Intra-operatively, meticulous attention to surgical technique, cell saver, INH, volume expantion, DDAVP, Vit K, Traneximic acid. Post-operatively, minimize blood taking for laboratory tests

23 Transfusion and the Peri-operative Patient
Hgb Recommendation > 100 g/L Likely inappropriate g/L Likely to be appropriate if there are signs or symptoms of impaired oxygen delivery < 70 g/L Likely to be appropriate. < 60 g/L Transfusion highly recommended

24 Transfusion and Chronic Anemia
Consider alternatives and adjuncts to transfusion Ensure adequate stores of iron, B12 & folate Erythropoietin Treat underlying disease Only transfuse when there is no effective alternative Maintain hemoglobin at a level avoid symptoms of anemia Monitor long-term transfusion dependant patients for iron overload

25 Frozen Plasma - Indications
1. Emergency reversal of warfarin therapy in a patient undergoing an emergency operation or with potentially life-threatening bleeding + should also include Vitamin K (10 mg i.v.) • Repeat PT/PTT after infusion of FP to ensure that replacement is adequate ◆ Patients with INR > 5 due to warfarin without bleeding • With INR > 5 and < 9, bring within the therapeutic range with 1-2 mg of oral Vitamin K

26 Frozen Plasma - Indications
• With INR ≥ 9, use 5-10 mg of oral vitamin K • SC and IM NOT recommended; use intravenous formulation orally, if oral tablets are not readily available • These patients do NOT require frozen plasma • After administration, Vitamin K effect can be detected after 2 hours and the INR should be normalized after hours

27 Frozen Plasma - Indications
2. Active bleeding/major surgery with PT/PTT more than 1.5 times normal10 3. Microvascular bleeding or massive transfusion AND patient’s clinical status precludes waiting minutes for PT/PTT results 4. Patients with liver disease-related coagulopathy for certain invasive procedures (percutaneous liver biopsy, paracentesis, thoracentesis) and INR > 2.0

28 Frozen Plasma Dose is mL/Kg, or mL for average sized adult Infusion time minutes (max 4 hrs) Transfuse slowly (50 mL/hr) for the first 15 minutes Monitor the patient closely for the first 15 minutes. Should be ABO compatible

29 Frozen Plasma Single dose should normalize INR/PT/PTT
Check INR/PT/PTT after Frozen plasma must be transfused through a blood administration filter (170–260 microns) FP is compatible ONLY with normal saline Frozen plasma is kept frozen for up to one year. ◆ The biological half-life of plasma coagulation proteins is different for each protein: • 3–6 hours for factor VII • 8–12 hours for factor VIII • 2–3 days for factors II and IX

30 Platelets Platelets for transfusion come in 4 forms:
Random donor, from single donation, contains > 5.5x1010 platelets; given in pools of 5, volume 300mL Apheresis (single donor) platelets; pack contains 30x1010 platelets,volume 300ml HLA-matched apheresis platelets, matched for specific recipients immunized against HLA antigens Pool of 4 units of buffy coat derived platelets

31 Platelets In non-bleeding patients, the risk of spontaneous hemorrhage is low when platelet count is greater than 10 x 109/L The bleeding time is NOT useful in predicting which thrombocytopenic patients are at risk. Relative Contraindications: ◆ Thrombotic thrombocytopenic purpura (TTP) ◆ Heparin induced thrombocytopenia (HIT) ◆ Post-transfusion purpura (PTP)

32 Platelets – Storage & Transfusion
Shelf life 5 days Stored at 20-24o C with constant mixing Longer storage increases risk of septic reaction Recommended infusion time 60 minutes One pool of 5 units of random donor platelets, or one apheresis platelet unit, should raise the platelet count by >15x109/L Check post-transfusion platelet count within 1 hour of transfusion to determine response and detect refractoriness Transfuse slowly (50 mL/hr) for the first 15 minutes Monitor the patient closely for the first 15 minutes

33 Platelets and Blood Group
ABO/RhD identical preferred ABO/RhD non-identical are acceptable Rarely, incompatible plasma in a platelet preparation may cause a hemolytic reaction due to high titre anti-A or anti-B RhD –ve females of child-bearing potential receiving RhD +ve platelets require Rh-immunoglobulin prophylaxis

34 Clinical Use of Platelets I.
Platelet count (x109/L) Clinical setting Recommend <10 Immune thrombocytopenia Transfuse platelets only with serious bleeding Non-immune thrombocytopenia Transfuse 5 unit pool or 1 unit of apheresis platelets Non-immune thrombocytopenia and HLA-immunized Transfuse 1 unit of HLA-matched apheresis platelets <20 Non-immune thrombocytopenia and fever >38.5oC or coagulopathy Procedures not associated with significant blood loss 20-50 Have pool of 5 units or 1 unit of apheresis platelets available, transfuse only if there is serious bleeding

35 Clinical Use of Platelets II.
Platelet count (x109/L) Clinical Setting Recommended <50 Epidural anesthesia and lumbar puncture Transfuse 5 unit pool or 1 unit of apheresis platelets immediately before procedure Procedures associated with blood loss or major surgery (>500 mL expected blood loss) <100 Pre-neurosurgery or head trauma Transfuse 5 unit pool or 1 unit of apheresis platelets Any Platelet dysfunction and marked bleeding (e.g. post-cardiopulmonary bypass, anti-platelet agents)

36 Cryoprecipitate Cryoprecipitate contains Fibrinogen
Von Willebrand Factor Clotting Factor VIII (anti-hemophilic factor) 1 unit per 8-10 Kg body weight, or 8-12 units for an average sized adult Infusion time minutes Each dose should raise fibrinogen by 0.5 g/L Check post-infusion fibrinogen level to confirm outcome

37 Clinical Use of Cryoprecipitate
Treatment of massive or microvascular bleeding with Fibrinogen less than 0.8 to 1.0 g/L Clinical status highly suggestive of a low fibrinogen concentration in the setting of massive bleeding and clinical status precludes waiting for fibrinogen result before transfusion Massive rapid defibrination in the obstetrical patient Hereditary Disorders of Hemostasis For bleeding in von Willebrand’s syndrome patients ONLY if factor concentrate is unavailable and DDAVP is ineffective For the emergency management of factor VIII deficiency ONLY if manufactured factor VIII is unavailable

38 Serious Hazards of Transfusion n=2087 Major Morbidity in UK for 1996-2003

39 Risk Charts Risk of Event Event 1 in 10
Febrile non-hemolytic transfusion reaction per pool of 5 donor units of platelets (5 ‘donor exposures’) per unit of component 1 in 100 Minor allergic reactions (urticaria) 1 in 300 Febrile non-hemolytic transfusion reaction per unit of RBC (1 ‘donor exposure’) 1 in 700 Transfusion-associated circulatory overload (TACO) per transfusion episode 1 in 5,000 Transfusion-related acute lung injury (TRALI)

40 Risk Charts 1 in 7,000 Delayed hemolytic transfusion reaction
Symptomatic bacterial sepsis, per pool of platelets that you receive 1 in 40,000 Death from bacterial sepsis, per pool of platelets that you receive Wrong ABO (blood) group, per unit of red blood cells that you receive Serious allergic reaction per unit of component 1 in 153,000 Hepatitis B (HBV) transmission per unit of component.

41 Risk Charts 1 in 100,000 Symptomatic bacterial sepsis, per unit of red blood cells that you receive 1 in 500,000 Death from bacterial sepsis, per unit of red blood cells that you receive. < 1 in 1,000,000 Transmission of West Nile Virus 1 in 3,100,000 Hepatitis C (HCV) transmission, per unit of componentHuman 1 in 4,300,000 T-cell lymphotropic virus (HTLV) transmission, per unit of component 1 in 5,000,000 Human Immunodeficiency Virus (HIV) transmission, per unit of component

42 Some Transfusion Risks compared with Risks of Everyday Life
Risk of Daily Life Magnitude of Risk Transfusion Risk Death from lung cancer after smoking a pack a day for 30 years 1 in 10 Febrile non-hemolytic transfusion reaction Death associated with hip replacement surgery 1 in 100 Urticarial reaction Annual risk of death from a motor vehicle crash 1 in 10,000 Symptomatic sepsis from a pool of 5 random donor platelets Annual risk of being murdered in Canada 1 in 60,000 Risk of contracting hepatitis B from a single unit is 35% less Annual risk of dying from a lightening strike 1 in 5,000,000 Risk of contracting HIV from a single unit

43 The 10 Commandments Base decisions on national guidelines
Minimize blood loss and use conservation measures In acute blood loss, use effective resuscitation while assessing transfusion needs Hemoglobin level not the only consideration in decision to transfuse Transfusion only one element in treatment Be aware of risks of transfusion

44 The 10 Commandments 7. Prescribe only when the benefits outweigh the risks 8. Clearly record the reason for transfusion 9. Monitor the first 15 minutes of the transfusion for adverse events 10. Obtain informed consent for transfusion of any blood product Must be given voluntarily and clearly documented Patient must have the capacity to give consent Consent must be specific to the treatment proposed Patient must understand the nature, risks and benefits

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