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1 CLINICAL PRACTICE CLINICAL PRACTICE OF OF TRANSFUSION MEDICINE TRANSFUSION MEDICINE DR. RAFIQ AHMAD

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CLINICAL PRACTICE CLINICAL PRACTICE OF OF

TRANSFUSION MEDICINETRANSFUSION MEDICINE

DR. RAFIQ AHMAD

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ContentsContents

Procurement and processing Clinical use of red cells, platelets, plasma, and

cryoprecipitate Adverse effects Alternatives Good transfusion practices

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Saudi Food and Drug Authority enforces strict standards for screening donors for collection, processing and distribution of

blood and components Saudi Ministry of Health Blood Services are responsible for

donor recruitment collection, processing and distribution of blood components referral centers

Hospitals hospital blood banks hospital transfusion services - also responsible for supply of manufactured products (e.g. albumin, clotting factor VIII)

BasicsBasics

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Types of donationsTypes of donations

1. Voluntary (including mobiles) -70% in RBB 1. Voluntary (including mobiles) -70% in RBB 2. Replacement – 30% in RBB2. Replacement – 30% in RBB3. Autologous and Directed Donations - rare3. Autologous and Directed Donations - rare

Autologous blood (patient’s own blood) may be collected in advance of elective surgery by blood center 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 the blood center

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Donor RegistrationDonor Registration

Each donation is registered by Identification, and 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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Donor ScreeningDonor Screening * Hb estimation

* Sickle cell testing * ABO grouping * Rh-D typing

Medical Examination * General Health * Pulse * BP * Temperature * Skin

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Testing the Donation I.Testing the Donation I.

All donations are tested for some infectious agents:

HIV by antigen/antibody, and NAT HCV by antibody, and NAT HBV by HBsAg/antibody to HBc

total and NAT HTLV by antibody Syphilis by antibody (RPR/TPHA) Malaria by slide

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Testing the Donation II.Testing the Donation II.Red cell type Antibodies present Recipient

CompatibilityApproximate frequency

Group O (no ABO antigens)

Anti-A, anti-B All ABO groups 42%

Group A Anti-B Groups A & AB 30%

Group B Anti-A Groups B & AB 20%

Group AB Neither present Group AB 08%

Rhesus group D positive

Normally none Should be RhD identical, RhD –ve acceptable

92%

Rhesus group D negative

Normally none Should be RhD identical

08%

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Removal of White Cells Removal of White Cells (Leukoreduction(Leukoreduction))

Leukoreduction: Most of 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 63mL 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 be crossed

Platelets (single donor apheresis)

5 days 20-24o C with constant mixing

Same as above. Anti-D prophylaxis required for some recipients

Fresh 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

Serious Hazards of Transfusion n=1148 Serious Hazards of Transfusion n=1148 Major Morbidity in UK for 1996-2001Major Morbidity in UK for 1996-2001

Wrong blood61%

Acute Hemolytic13%

Delayed Hemolytic12%

TRALI6%

PT-Purpura3%

Infectious3%

GVH1%

Other1%

Other5%

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National Haemovigilance Programme, SingaporeNational Haemovigilance Programme, SingaporeAug 2004 - Dec 2007 (total reported cases 1,939)Aug 2004 - Dec 2007 (total reported cases 1,939)

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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 cells Patient testing Selection of compatible units Expected outcome of transfusion Good transfusion practices Guidelines 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 of 160mL of red cells 60mL of plasma 60mL of anticoagulant (citrate) and preservative

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Blood Grouping ProcedureBlood Grouping Procedure

Upper image: reactions determining the ABO and RhD type

Lower image: antibody screening reactions on 3 patients.

Middle 2 tubes: unexpected antibody to screening cell 1

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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

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

Assess the outcome (clinical, hemoglobin level) before transfusing further

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The 10 FactsThe 10 Facts

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 Facts contd…The 10 Facts contd…

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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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

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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

Intra-operatively, meticulous attention to surgical technique

Post-operatively, adhere to good transfusion practice, minimize blood taking for laboratory tests

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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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PlateletsPlatelets

Platelets for transfusion come in 3 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,volume300m HLA-matched apheresis platelets,

matched for specific recipients immunized against HLA antigens

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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 >30x109/L

Check post-transfusion platelet count within 1 hour of transfusion to determine response and detect refractoriness

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Platelet transfusion responsePlatelet transfusion response

1. Calculation of Corrected Count Increment (CCI) in m² BSA/µL

CCI = Platelet count Increment X m² BSA/N

2. Post Platelet Recovery (PPR) in %age

PPR = Platelet count Increment X Blood Volume /N

N= Numbers of platelets transfusedNIH guidelines * 2 consecutive CCI of < 5000 platelets x m² BSA/µL indicates refractoriness after 1 hr

* PPR of < 20 % also indicates refractoriness

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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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Fresh Frozen PlasmaFresh Frozen Plasma

Fresh Frozen Plasma is a source of

clotting factors, with half lives in vivo

of between 6 hours & 3 days. Available in 2 forms:

250 mL recovered from regular donations 500 mL from apheresis donation

30 minutes required for thawing

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Fresh Frozen Plasma Fresh Frozen Plasma Dose and InfusionDose and Infusion

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

Infusion time 30-120 minutes Should be ABO compatible Single dose should restore

INR/PT/PTT to normal Check INR/PT/PTT after

infusion to confirm outcome

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Reversal of Warfarin EffectReversal of Warfarin Effect

Warfarin effect can be reversed with vitamin K, 10 mg iv, and should be preferred to transfusion if time permits

If not, 750-1000 mL should be transfused

Expected result, INR/PT/PTT 1.5 x normal or less

Failure to get this result, re-consider diagnosis

Warfarin reversal effect

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Misuse of Frozen Plasma - AuditMisuse of Frozen Plasma - Audit

CMAJ 2002; 166: 1539.CMAJ 2002; 166: 1539.

Almost half of 358 patients received FFP outside of guidelines– Appropriate 55%– Bleeding with INR<1.5 29%– Not bleeding 9%– INR not done 4%– Other 3%

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CryoprecipitateCryoprecipitate

Cryoprecipitate containsFibrinogen – 250mgVon Willebrand FactorClotting Factor VIII (anti-hemophilic factor) – 80IU

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 500 mg/dL Check post-infusion fibrinogen level to confirm outcome

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DoseDose

Fibrinogen dose = Fibrinogen increment x Plasma Volume/100/250

1 bag contains 250 mg/dL of fibrinogen

Cryoppt. dose) = factor VIII level increment x Plasma Volume/100/80

1 bag contains 80 IU of factor VIII

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Clinical Use of CryoprecipitateClinical Use of Cryoprecipitate

Treatment of massive or microvascular bleeding with Fibrinogen < 1.0 g/L Status highly suggestive of hypofibrinogenemia without time for

laboratory confirmation 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

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The end !!

Thank you