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Blood Bank and Transfusion Pathology

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1. Historical Milestones

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2. Blood Donation and Screening

• Hepatitis B and C
• HIV-1 and HIV-2
• Syphilis

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3. Blood Groups

ABO System

• Group O = Universal donor (no antigens to provoke a reaction)
• Group AB = Universal recipient (no circulating antibodies)

Rhesus (Rh) System

• The Rh(D) antigen is strongly antigenic; present in ~85% of the UK population
• Anti-D antibodies are not naturally occurring - they are stimulated by transfusion of Rh+ blood or delivery of an Rh(D)+ baby
• Anti-D crossing the placenta in an Rh(D)-negative mother can cause haemolytic disease of the newborn (HDN) - severe haemolytic anaemia or hydrops fetalis

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4. Blood Products

Whole Blood

• Rarely available in civilian practice; replaced by component therapy
• Advantages: coagulation factor-rich, metabolically active if fresh
• Indications: acute blood loss replacement, volume expansion in septicaemia with coagulopathy

Packed Red Blood Cells (pRBCs)

• Each unit ~330 mL, haematocrit 50-70%
• Stored in SAG-M (saline-adenine-glucose-mannitol) solution at 2-6°C
• Shelf life: 5 weeks (older CPD storage: 2-3 weeks)

Fresh Frozen Plasma (FFP)

• Rich in all coagulation factors
• Stored at -40 to -50°C; shelf life 2 years
• First-line therapy for coagulopathic haemorrhage
• Note: Rh(D)-positive FFP can be given to Rh(D)-negative women, but seroconversion is possible with large volumes due to red cell fragments - consider Rh-D immunisation prophylaxis

Cryoprecipitate

• Supernatant precipitate of FFP
• Rich in: fibrinogen, Factor VIII, Factor XIII
• Stored at -30°C; shelf life 2 years
• Indications: low-fibrinogen states, Factor VIII deficiency

Platelets

• Pooled concentrate: ~250 × 10⁹/L
• Stored on a special agitator at 20-24°C; shelf life only 5 days
• Given for thrombocytopenia or platelet dysfunction in bleeding/surgery
• Patients on clopidogrel who are actively bleeding may need near-continuous infusion; DDAVP has limited success

Prothrombin Complex Concentrates (PCC)

• Highly purified; contains Factors II, IX, X (±VII)
• Indicated for emergency reversal of warfarin in uncontrolled haemorrhage
• Dose: 25-50 units/kg based on INR; preferred over FFP for warfarin reversal (BCSH 2012 guidelines)

Autologous Blood

• Pre-donation up to 3 weeks before elective surgery for re-transfusion
• Cell salvage: intraoperative collection, washing, and reinfusion of red cells

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5. Indications and Transfusion Trigger

1. Acute blood loss (restore circulating volume and O₂ delivery)
2. Perioperative anaemia
3. Symptomatic chronic anaemia

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6. Cross-Matching

• Full cross-match (ABO + Rh typing + recipient serum vs donor cells): takes up to 45 minutes
• "Type-specific" blood (ABO/Rh matched only): available within 10-15 minutes
• Emergency: Group O blood (O- for females of childbearing age; O+ for males)

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7. Transfusion Reactions

Acute Reactions

Immediate Haemolytic Transfusion Reaction (IHTR)

• Caused by ABO incompatibility - usually clerical/human error (~1 in 180,000 red cells transfused)
• Mechanism: IgM complement-fixing anti-A/anti-B antibodies cause intravascular haemolysis
• Consequences: cytokine release, activation of coagulation, renal failure, DIC
• Features: pain at infusion site, chest and back pain, hypotension, haemoglobinuria
• Mortality: up to 10%

Febrile Non-Haemolytic Transfusion Reaction (FNHTR)

• Caused by recipient's anti-leucocyte antibodies reacting with leukocytes in transfused components
• Features: fever, chills/rigors, nausea, muscle pain
• Temperature rise >38°C but <2°C above baseline: slow transfusion + antipyretics (paracetamol)
• Temperature >39°C or rise >2°C: stop transfusion
• Now rare with leukodepleted blood

Allergic Reaction / Anaphylaxis

• Mild (urticaria, flushing): slow infusion, antihistamines
• Severe anaphylaxis (wheeze, stridor, angioedema): IM adrenaline + IV chlorpheniramine + IV hydrocortisone

TRALI - Transfusion-Related Acute Lung Injury

• Typically after platelets or FFP (multi-parous female donors are higher risk)
• Mechanism: Two-hit model
  1. Donor anti-leukocyte antibodies (HLA class I/II or neutrophil-specific antigen antibodies) react with recipient neutrophils - "first hit"
  2. Bioactive lipids/cytokines stored in blood products activate primed pulmonary neutrophils - "second hit"
• Features: severe hypoxia, hypotension, bilateral lung infiltrates within 6 hours of transfusion
• Distinguishing from ARDS or TACO is important
• Treatment: supportive - high-flow oxygen, ventilator support if needed

TACO - Transfusion-Associated Circulatory Overload

• Common in elderly and cardiac patients; frequently underdiagnosed
• Defined as: acute/worsening pulmonary oedema within 6 hours of transfusion
• Features: dyspnoea, tachycardia, hypertension (key distinction from TRALI), positive fluid balance
• Treatment: stop transfusion, oxygen, diuretics
• Prevention: co-administration of diuretics, single unit transfusions in frail adults

Approach to Acute Transfusion Reaction (BOX - Scott-Brown's)

1. Stop the transfusion
2. Assess: Airway, Breathing, Circulation
3. Maintain IV access with physiological saline
4. Check patient ID and blood component compatibility
5. Inspect component for clumps/discolouration
6. Assess for evidence of blood loss
7. (Unless mild allergic/febrile): FBC, renal/liver screen, blood culture, direct Coombs test, repeat group & screen, urine for haemoglobinuria
8. Inform the transfusion laboratory
9. Return blood component to the transfusion laboratory
10. Report to SHOT (Serious Hazards of Transfusion)

SHOT Report Data (Cumulative 1996-2012)

Delayed Reactions

Delayed Haemolytic Transfusion Reaction (DHTR)

• Occurs days after transfusion in previously sensitized individuals (prior transfusions or pregnancy)
• Mechanism: alloantibodies (Rh, Kell, Duffy) had fallen below detectable levels; re-exposure triggers a secondary IgG immune response and extravascular haemolysis
• Features: jaundice, haemoglobinuria, fever, fatigue, anaemia; rarely renal failure
• Investigations: drop in Hb, positive direct Coombs test, raised bilirubin

Post-Transfusion Purpura (PTP)

• Severe thrombocytopenia (platelets <10 × 10⁹/L) 7-12 days post-transfusion
• Occurs in previously pregnant/transfused females who are HPA-1a antigen negative
• Develops high anti-HPA-1a levels after transfusion
• Treatment: high-dose IV immunoglobulin; now rare since leukodepletion

Transfusion-Associated Graft Versus Host Disease (TA-GVHD)

• Rare but usually fatal
• Cause: donor lymphocytes engraft in recipient and mount immune attack
• Features: fever, rash, diarrhoea, jaundice, bone marrow failure (appearing up to 30 days post-transfusion)
• At-risk: immunocompromised patients (congenital immunodeficiency, HIV, post-BMT, fludarabine therapy)
• Prevention: gamma-irradiated blood components

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8. Complications of Massive Transfusion

Management of Coagulopathy in Massive Haemorrhage

• Damage control resuscitation: deliver matched RBC : FFP : platelets in 1:1:1 ratio (approximates whole blood)
• Tranexamic acid: empirically, as early as possible - most bleeding patients are hyperfibrinolytic
• Cryoprecipitate: for low fibrinogen (guided by TEG/ROTEM or empirically)
• Avoid crystalloids and colloids if at all possible (dilute clotting factors)
• Frequent point-of-care coagulation testing (thromboelastometry)

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9. Infection Transmission Risk

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10. Blood Substitutes

• Biomimetic (haemoglobin-based): engineered molecules from human, bovine or recombinant sources; one free Hb solution commercially available in some countries
• Abiotic (perfluorocarbon-based): synthetic oxygen carriers; second-generation emulsions in clinical trials
• No widely approved substitute available yet in most countries

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Summary of Key Safety Points

• Always confirm patient identity and blood compatibility with two healthcare personnel before transfusion
• The commonest cause of fatal reactions is ABO incompatibility due to clerical error - not inherent product failure
• Universal leukodepletion has significantly reduced FNHTR and TA-GVHD
• In active haemorrhage, a 1:1:1 ratio of RBC:FFP:platelets plus tranexamic acid is standard damage control resuscitation
• For warfarin reversal: PCC + vitamin K preferred over FFP
• High-risk patients (immunocompromised) must receive gamma-irradiated components to prevent TA-GVHD

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