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