Blood Products for Transfusion - Complete Exam Guide

Overview: Component Therapy Philosophy

1. PACKED RED BLOOD CELLS (pRBCs)

Preparation

• Whole blood is centrifuged into 3 layers: RBCs (bottom), buffy coat (WBCs + platelets, middle), plasma (top)
• Plasma is removed and frozen (becomes FFP)
• Remaining RBCs + buffy coat pass through a leukoreduction (LR) filter - removes essentially all WBCs
• Final product: ~350 mL, hematocrit 55-65%

Storage

• Anticoagulant/preservative solution (SAGM - Saline, Adenine, Glucose, Mannitol, or CPD - Citrate Phosphate Dextrose)
• Temperature: 2-6°C
• Shelf life: 42 days (with SAGM additive; older CPD solutions: 21 days)

Indications

• Symptomatic anaemia
• Restrictive transfusion strategy thresholds (AABB 2016 guidelines):
  • Hb < 7 g/dL - most critically ill patients, general surgical patients
  • Hb < 8 g/dL - orthopedic surgery, cardiac surgery, pre-existing cardiovascular disease
  • Hb < 9 g/dL - known symptomatic coronary artery disease or ongoing cardiac ischaemia
  • Hb < 10 g/dL - active cardiac ischaemia (some guidelines)
• Exsanguinating hemorrhage: transfuse emergently regardless of Hb (untyped O-negative or O-positive)

Dose

• 1 unit pRBC raises Hb by ~1 g/dL (or Hct by ~3%) in a 70 kg adult
• In pediatrics: 4-5 mL/kg raises Hb by ~1 g/dL

2. FRESH FROZEN PLASMA (FFP)

Preparation

• Plasma from whole blood centrifugation, frozen at -18° to -30°C within 8 hours of procurement
• "PF-24" = frozen between 8-24 hrs; "Thawed plasma" = FFP/PF-24 thawed but not immediately used
• Contains all clotting factors at physiological levels
• Volume: ~200-250 mL per bag

Storage

• -18° to -30°C (some sources say -40° to -50°C for maximum preservation)
• Shelf life: 2 years (frozen); once thawed must be used within 4 hours (or within 5 days if stored at 1-6°C as "thawed plasma")
• Available for use in 45-60 minutes (thawing time is a practical limitation)

Indications

• Coagulopathic haemorrhage (INR > 1.5 with bleeding)
• Massive transfusion protocol (1:1:1 ratio)
• Reversal of warfarin in active life-threatening bleeding (alongside Vitamin K, but 4-factor PCC is preferred)
• DIC with bleeding
• Thrombotic thrombocytopenic purpura (TTP) - plasma exchange uses FFP
• Note: FFP cannot correct INR below 1.5 - it is ineffective for mildly elevated INR (< 2.0)

Dose

• 15 mL/kg, or approximately 4 units (~1,000 mL) in a 70 kg adult
• Each unit raises all coagulation factors by 2-3% in average-sized adults
• Minimum of 4 units needed to meaningfully correct an elevated INR

ABO compatibility

• ABO-compatible preferred; Rh compatibility is not required for FFP (though Rh-D positive FFP given to Rh-negative woman can cause rare seroconversion due to red cell fragments)

3. CRYOPRECIPITATE ("Cryo")

Preparation

• Made by thawing FFP slowly at 4°C, then centrifuging - the cold-insoluble precipitate (cryoprecipitate) is separated and refrozen
• Resuspended in ~15-20 mL of plasma
• Often pooled from multiple donors
• Rich in: Fibrinogen, Factor VIII, Factor XIII, von Willebrand Factor (vWF), Fibronectin

Storage

• -30°C (or -18°C)
• Shelf life: 2 years (frozen); once thawed must be used promptly (within 4-6 hours)
• Available in approximately 20 minutes (faster to prepare than FFP)

Indications

• Hypofibrinogenaemia (fibrinogen < 100 mg/dL) - the primary indication
• DIC with low fibrinogen
• Bleeding after fibrinolytic therapy (e.g., tPA)
• Factor VIII deficiency (Haemophilia A) - when specific factor concentrates unavailable
• vWF disease - when DDAVP fails
• Factor XIII deficiency

Dose

• 10 bags for hypofibrinogenaemia (fibrinogen < 100 mg/dL)
• 10-12 bags for fibrinolytic-induced bleeding
• 1 bag per 5 kg for Factor VIII deficiency (raises factor VIII to ~50% of normal)
• Each bag raises fibrinogen by ~50 mg/dL in average adults (rough estimate)

4. PLATELETS

Preparation

1. Random donor (whole blood-derived): "Soft spin" then "hard spin" centrifugation; pooled from 4-6 donors = "6-pack"
2. Single-donor apheresis (preferred): Blood continuously cycled through a centrifuge machine over 2-3 hours; single donor reduces infectious and immunological risk; an apheresis pack ≈ one 6-pack in platelet count

Storage

• 20-24°C (room temperature) with continuous gentle agitation
• Shelf life: 5-7 days (short! This is clinically important)
• Volume: 30-50 mL per individual unit; ~180-300 mL per 6-pack/apheresis unit

Indications

• Active haemorrhage with thrombocytopenia
• Massive transfusion (1:1:1 ratio)
• Maintain > 50,000/μL in GI bleed patients
• Note: Do NOT transfuse empirically in patients on antiplatelet drugs (ASA/clopidogrel) who are NOT thrombocytopenic
• In ITP, transfused platelets are rapidly destroyed - benefit is transient

Dose

• 1 unit per 10 kg body weight
• Equivalent to: 1 apheresis pack or a 4-6 pack of pooled random-donor platelets
• Expected rise: each unit → 5,000-10,000/μL increase; a 6-pack or 1 apheresis unit → 30,000-60,000/μL increase
• For clopidogrel/ASA reversal: use 3x the usual dose

ABO compatibility

• ABO and Rh compatible preferred, but not required in emergency

5. WHOLE BLOOD

• Rarely available in civilian practice; standard in military trauma
• Low Titer Group O Whole Blood (LTGOWB) - used in military for unknown blood group patients
• Advantages: coagulation factor-rich, more metabolically active than stored blood
• Storage: 2-6°C, up to 35 days (retains platelet functionality in vivo)
• Increasingly used at civilian trauma centers in hemorrhagic shock resuscitation

6. OTHER/SPECIAL PRODUCTS

Factor Concentrates

• 4-Factor Prothrombin Complex Concentrate (PCC): Contains factors II, VII, IX, X + Protein C/S - preferred over FFP for reversal of Vitamin K antagonists (warfarin) in active bleeding; faster and more effective; also used in ICH
• Recombinant Factor VIIa (rFVIIa): Used in haemophilia A with Factor VIII inhibitors; off-label use in massive hemorrhage (increased arterial clot risk, no proven mortality benefit in non-haemophiliacs)
• Factor VIII / Factor IX concentrates: Specific replacement in Haemophilia A/B

TRANSFUSION REACTIONS & COMPLICATIONS

Frequency Table (per unit transfused, USA)

A. Acute Haemolytic Transfusion Reaction (AHTR)

• Mechanism: Preformed recipient antibodies + transfused RBC antigens → antigen-antibody complex → complement activation → intravascular haemolysis
• Most commonly from ABO incompatibility (clerical/administrative errors account for most)
• Triggered by as little as 10 mL of incompatible blood
• Symptoms: Fever, chills, back/flank pain, chest pain, nausea, haemoglobinuria, hypotension
• Under general anaesthesia, masked symptoms - look for: haemoglobinuria, unexplained hypotension, bleeding diathesis (DIC)
• Plasma turns pink/red when free Hb > 2 mg/dL
• Complications: AKI (haemoglobin tubular toxicity), DIC, death
• Management:
  1. Stop transfusion immediately
  2. Maintain IV access (normal saline, not blood)
  3. Maintain urine output > 1 mL/kg/hr (IVF ± furosemide/mannitol)
  4. Send samples: recheck blood group/cross-match, DAT, plasma Hb, urine Hb, coagulation screen
  5. Notify blood bank
  6. Treat DIC if it develops

B. Febrile Non-Haemolytic Transfusion Reaction (FNHTR)

• Most common transfusion reaction
• Temperature rise ≥ 1°C or > 38°C within 4 hours of transfusion cessation
• Mechanism:
  • Platelets: cytokines that accumulate during storage
  • RBCs: donor leukocytes reacting with patient WBC antibodies
• Incidence greatly reduced by leukoreduction
• Management: Stop transfusion, exclude AHTR (send samples), restart at slower rate if confirmed FNHTR; paracetamol pre-medication for future transfusions

C. Allergic Transfusion Reaction

• Mild (urticaria, pruritis, flushing): Stop transfusion, give antihistamine, restart when resolved
• Severe/Anaphylaxis (stridor, bronchospasm, hypotension, shock): Stop transfusion permanently; epinephrine, H1-antihistamine, corticosteroids
• Special case: Anti-IgA antibodies in IgA-deficient patients → anaphylaxis; requires IgA-deficient donor products or washed cells
• Platelets most commonly associated with allergic reactions

D. Transfusion-Associated Circulatory Overload (TACO)

• Incidence: ~1 : 9,000
• Risk factors: Age > 70, positive fluid balance > 3L, multiple units within 6 hours, cardiac/renal impairment
• Symptoms: Dyspnoea, orthopnoea, tachypnoea, cough, hypertension, cyanosis; onset within 6-12 hours of transfusion
• Elevated BNP/NT-proBNP (> 1000 pg/mL post-transfusion)
• Management: Stop transfusion, sit upright, oxygen, diuretics (furosemide)

E. Transfusion-Related Acute Lung Injury (TRALI)

• Incidence: ~1 : 140,000; leading cause of transfusion-related death
• Mechanism: Donor antibodies (anti-HLA or anti-neutrophil antibodies) activate recipient neutrophils → bilateral pulmonary capillary leak
• Onset: Within 6 hours of transfusion
• Symptoms: Acute hypoxia (PaO2/FiO2 < 300), bilateral pulmonary infiltrates on CXR, NO signs of circulatory overload; fever, hypotension
• Distinction from TACO: TRALI = non-cardiogenic (low BNP, no hypertension, low PCWP); TACO = cardiogenic (high BNP, hypertension)
• Management: Stop transfusion, supportive care (oxygen, mechanical ventilation if needed), NO steroids proven effective; usually resolves within 48-96 hours

F. Delayed Haemolytic Transfusion Reaction (DHTR)

• Occurs 3-14 days after transfusion
• Due to anamnestic (secondary) antibody response to non-ABO antigens (Kidd, Duffy, Kell, etc.) in a previously sensitised patient
• Extravascular haemolysis (reticuloendothelial system)
• Symptoms: Unexpected fall in Hb, fever, mild jaundice, positive DAT
• Usually self-limiting

G. Transfusion-Associated Graft-versus-Host Disease (TA-GvHD)

• Extremely rare (< 1 : 10,000,000) but almost universally fatal (>90% mortality)
• Donor lymphocytes proliferate and attack recipient tissues
• Prevention: Irradiation of blood products for immunocompromised patients
• Irradiated products indicated for: immunocompromised patients, bone marrow transplant recipients, neonates, directed donations from relatives, patients on purine analogue chemotherapy

H. Infectious Complications (Residual Risk, USA)

I. Massive Transfusion Complications

• Hypothermia - use blood warmers
• Hypocalcaemia - citrate in stored blood chelates calcium; replace with IV calcium gluconate/chloride
• Hyperkalaemia - stored blood releases K+ (especially old units); monitor ECG
• Metabolic alkalosis - citrate is metabolised to bicarbonate
• Coagulopathy/Dilutional - replace with FFP, platelets, cryoprecipitate in 1:1:1 ratio

QUICK-REFERENCE STORAGE SUMMARY

PRACTICAL SKILLS CHECKLIST

1. Before ANY transfusion:
   • 2 patient identifiers verified (name + DOB)
   • Blood product label checked against patient wristband at bedside
   • Consent documented
   • Baseline obs (temp, HR, BP, SpO2)
2. Administration:
   • Use a blood giving set (170-200 μm filter) - do NOT use the same line as dextrose (causes haemolysis)
   • Normal saline is the only compatible IV fluid to run concurrently
   • Infuse within 4 hours of issue
   • First 15 minutes: observe closely at slow rate (5 mL/min); if no reaction, increase rate
3. If reaction suspected:
   • Stop transfusion, keep IV line open with normal saline
   • Check identity - was the right blood given to the right patient?
   • Obs, notify blood bank, send: patient + bag samples back to blood bank, blood cultures, FBC, coagulation, U&E, LDH, bilirubin, DAT, urine for Hb