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Transfusion MedicineTransfusion Medicine

22/March/2010Mazin Jan, MD, FRCPC

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Transfusion Medicine BasicsTransfusion Medicine Basics

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Transfusion: Risks and Informed ConsentTransfusion: 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

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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)

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Autologous and Directed DonationAutologous 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

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Donor ScreeningDonor 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

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Testing the Donation I.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 Group AB 3%

Rhesus group D positive

Normally none Should be RhD identical, RhD –ve acceptable

85%

Rhesus group D negative

Normally none Should be RhD identical

15%

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Testing the Donation II.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 solabeled

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Removal of White Cells (Leukoreduction)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

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Making ComponentsMaking 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

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Components – Shelf-life, Storage & CompatibilityComponents – Shelf-life, Storage & Compatibility

Component Shelf-life Storage 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)

5 days 20-24o C with constant mixing

be crossed. Anti-D prophylaxis required for some recipients

Frozen plasma 12 months Minus 18o C or lower

ABO compatible preferred

Cryoprecipitate 12 months Minus 18o C or lower

ABO compatible preferred

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Importance of Patient Identification Importance of Patient Identification to Safe Transfusion Practiceto 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

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When to Order “Group & Screen” When to Order “Group & Screen” and When to Consider Cross-matchand 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 GroupScreen

Cross-matchAntibody Screen

Anti-globulin cross-match, or abbreviated cross-match

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Red Blood Cell TransfusionRed Blood Cell Transfusion

This section covers:Contents of a unit of red cellsPatient testingSelection of compatible unitsExpected outcome of transfusionGood transfusion practicesGuidelines for use of red cells

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Red Blood Cells for TransfusionRed Blood Cells for Transfusion

A unit of red cells contains 280mL, made up of160mL of red cells60mL of plasma60mL of anticoagulant

(citrate) and preservative

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Selecting Compatible Red Cells I.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

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Selecting Compatible Red Cells II.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

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Transfusion of Red CellsTransfusion of Red Cells

RBCs must be transfused through a blood administration filter (170-260 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

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Transfusion of Red CellsTransfusion 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.

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Transfusion in Acute Blood LossTransfusion 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 (80-100 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

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Transfusion in the Critically IllTransfusion 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

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Transfusion and the Peri-operative PatientTransfusion 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

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Transfusion and the Peri-operative PatientTransfusion and the Peri-operative Patient

Hgb Recommendation

> 100 g/L Likely inappropriate

70-100 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

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Transfusion and Chronic AnemiaTransfusion 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

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Frozen Plasma - IndicationsFrozen 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

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Frozen Plasma - IndicationsFrozen 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 12-24 hours

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Frozen Plasma - IndicationsFrozen 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 30-45 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

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Frozen PlasmaFrozen Plasma

Dose is 10-15 mL/Kg, or 750-1000 mL for average sized adult

Infusion time 30-120 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

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Frozen PlasmaFrozen 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

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PlateletsPlatelets

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

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PlateletsPlatelets

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)

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Platelets – Storage & TransfusionPlatelets – 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

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Platelets and Blood GroupPlatelets 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

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Clinical Use of Platelets I.Clinical Use of Platelets I.

Platelet count (x109/L)

Clinical setting Recommend

<10 Immune thrombocytopenia Transfuse platelets only with serious bleeding

<10 Non-immune thrombocytopenia Transfuse 5 unit pool or 1 unit of apheresis platelets

<10 Non-immune thrombocytopenia and HLA-immunized

Transfuse 1 unit of HLA-matched apheresis platelets

<20 Non-immune thrombocytopenia and fever >38.5oC or coagulopathy

Transfuse 5 unit pool or 1 unit of apheresis platelets

<20 Procedures not associated with significant blood loss

Transfuse 5 unit pool or 1 unit of apheresis platelets

20-50 Procedures not associated with significant blood loss

Have pool of 5 units or 1 unit of apheresis platelets available, transfuse only if there is serious bleeding

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Clinical Use of Platelets II.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

<50 Procedures associated with blood loss or major surgery (>500 mL expected blood loss)

Transfuse 5 unit pool or 1 unit of apheresis platelets immediately before procedure

<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)

Transfuse 5 unit pool or 1 unit of apheresis platelets

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CryoprecipitateCryoprecipitate

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 10-30 minutes Each dose should raise fibrinogen by 0.5 g/L Check post-infusion fibrinogen level to confirm outcome

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Clinical Use of CryoprecipitateClinical 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

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

Wrong blood66%

Acute Hemolytic11%

Delayed Hemolytic10%

TRALI7%

PT-Purpura2%

Infectious2%

GVH1% Other

1%

Other4%

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Risk ChartsRisk 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)

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Risk ChartsRisk Charts

1 in 7,000 Delayed hemolytic transfusion reaction

1 in 10,000 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

1 in 40,000 Wrong ABO (blood) group, per unit of red blood cells that you receive

1 in 40,000 Serious allergic reaction per unit of component

1 in 153,000 Hepatitis B (HBV) transmission per unit of component.

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Risk ChartsRisk 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

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Some Transfusion Risks compared with Risks Some Transfusion Risks compared with Risks of Everyday Lifeof 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

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The 10 CommandmentsThe 10 Commandments

1. Base decisions on national guidelines2. Minimize blood loss and use conservation

measures3. In acute blood loss, use effective resuscitation

while assessing transfusion needs4. Hemoglobin level not the only consideration in

decision to transfuse5. Transfusion only one element in treatment6. Be aware of risks of transfusion

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The 10 CommandmentsThe 10 Commandments

7. Prescribe only when the benefits outweigh the risks

8. Clearly record the reason for transfusion9. Monitor the first 15 minutes of the transfusion for

adverse events10. 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