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Massive Blood Transfusion and Blood Components

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I. BLOOD COMPONENTS - TYPES AND CHARACTERISTICS (8 marks)

1. Packed Red Blood Cells (PRBCs)

• Volume: ~250 mL per unit; haematocrit 55-80%
• Indication: Symptomatic anaemia, acute haemorrhage
• Storage: 1-6°C; shelf life 35-42 days (depending on preservative - CPDA-1, AS-3, etc.)
• Effect: 1 unit raises Hb by ~1 g/dL and haematocrit by ~3% in an average adult; 10-15 mL/kg raises Hb by 2-3 g/dL in children
• Transfusion time: 60-90 min in stable patients; should not exceed 4 hours (bacterial growth risk)
• Universal donor: Type O Rh-negative
• Universal recipient: Type AB
• Special preparations: leukocyte-reduced, irradiated, washed, frozen PRBCs

2. Fresh Frozen Plasma (FFP)

• Volume: 200-250 mL per unit
• Contains: All coagulation factors (both labile V and VIII), fibrinogen, inhibitors (antithrombin, protein C and S), albumin
• Preparation: Frozen within 8 hours of collection; stored at -18°C or below; shelf life 12 months (up to 24 months at -65°C)
• Thawing: Must be thawed at 37°C; use within 24 hours once thawed
• Indications:
  • Multiple coagulation factor deficiency (liver disease, DIC, massive transfusion)
  • Reversal of warfarin when PCC unavailable
  • TTP (plasma exchange)
  • Isolated factor deficiencies when specific concentrates unavailable
• Dosing: 10-15 mL/kg; 1 unit of any coagulation factor activity = clotting activity in 1 mL FFP
• ABO compatibility required; no Rh typing required
• Risks: TRALI (most commonly associated with multiparous female donors), allergic reactions, volume overload

3. Platelets

• Volume: ~55 mL (whole-blood derived) or 200-300 mL (apheresis/single-donor)
• Storage: 20-24°C on continuous agitation; shelf life 5-7 days
• One apheresis unit ≡ approximately 6 whole-blood-derived units
• Effect: 1 unit raises platelet count by ~5,000-10,000/μL in average adult
• Indications:
  • Platelet count <10,000/μL (prophylactic)
  • Count <50,000/μL with active bleeding or before invasive procedure
  • Count <100,000/μL in CNS surgery or ophthalmic surgery
  • Platelet function disorders with clinical bleeding
• ABO compatibility preferable but not always required; Rh-negative platelets preferred for Rh-negative premenopausal women (RBC contamination can cause Rh sensitisation)
• Leukocyte-reduced platelets reduce HLA sensitisation

4. Cryoprecipitate

• Preparation: Obtained by slowly thawing rapidly frozen (single-donor) plasma at 1-6°C; the precipitate is refrozen
• Volume: 5-20 mL per unit
• Contents per unit (minimum standards per AABB): fibrinogen ≥150 mg (assumes ~250 mg/unit), factor VIII ≥80 IU, also contains factor XIII, von Willebrand factor (vWF), and fibronectin
• Indications:
  • Hypofibrinogenaemia (fibrinogen <1.5 g/L with active bleeding) - the PRIMARY indication
  • DIC with fibrinogen deficiency
  • Congenital afibrinogenaemia/dysfibrinogenaemia
  • Haemophilia A and vWD when recombinant concentrates unavailable
  • NOT useful in haemophilia B (no factor IX)
• Dosing: Pool of up to 10 units for adults; expected rise ~50-70 mg/dL fibrinogen
• Formula for dosing: [Desired fibrinogen - Initial fibrinogen] × [Patient plasma volume] / 250 mg per unit
• ABO compatibility preferred (minor incompatibility risk) though not strictly required in adults

5. Prothrombin Complex Concentrate (PCC)

• Three-factor PCC: factors II, IX, X (lacks significant factor VII)
• Four-factor PCC: factors II, VII, IX, X + protein C and S (preferred for warfarin reversal)
• Indication: Life-threatening warfarin-associated haemorrhage or intracranial haemorrhage; more rapid INR normalisation than FFP; achieves INR <1.5 within 1 hour
• Always co-administer Vitamin K 10 mg slow IV (1 mg/min)

6. Whole Blood / Low-Titer O Universal Whole Blood (LTOWB)

• Gaining renewed interest especially in damage-control resuscitation and military settings
• LTOWB: Type O donors with anti-A and anti-B titer <256 (saline method); safe in non-group O recipients when up to 4 units given
• Contains all blood components in physiologic ratio; simplifies logistics

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II. PRE-TRANSFUSION TESTING (3 marks)

• (Coombs reagent) = anti-human globulin; promotes agglutination of sensitised RBCs
• Type O Rh-positive can be used in males and post-menopausal women if O Rh-negative unavailable; avoid in females of childbearing potential (~20% develop anti-Rh(D) with 1 unit)

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III. MASSIVE BLOOD TRANSFUSION (MBT) (10 marks)

Definition

• Classical: Transfusion of ≥10 units PRBCs within 24 hours (approximately one circulating blood volume in an adult ~70 mL/kg)
• Practical/operational: Transfusion of ≥3 units PRBCs/hour or ≥4 components in 30 minutes - triggers MTP activation
• Alternative: Transfusion of >50% circulating blood volume in 3 hours

Indications for Massive Transfusion

1. Major trauma with haemorrhagic shock
2. Ruptured aortic aneurysm
3. Gastrointestinal haemorrhage
4. Obstetric catastrophe (postpartum haemorrhage, placenta praevia/accreta)
5. Major intraoperative haemorrhage (hepatic surgery, cardiac surgery, vascular surgery, spine surgery)

Massive Transfusion Protocol (MTP)

• 6 units PRBCs + 6 units FFP + 1 apheresis platelet unit (equivalent of 6 whole-blood platelets)
• This represents a 1:1:1 ratio (PRBC : FFP : Platelets)

• Acute haemorrhage involves loss of whole blood - not selective loss of RBCs alone
• The PROPPR Trial (multicentre RCT): Compared 1:1:1 vs 1:1:2 (PRBC:FFP:Platelets) - no difference in 24-hour or 30-day mortality, but fewer deaths from exsanguination at 24 hours with 1:1:1 ratio
• Current recommendation: 1:1:1 ratio (PRBCs : FFP : Platelets)
• Note: Some evidence suggests 1:1:2 strategy may be equally efficacious in certain populations

Damage Control Resuscitation (DCR) Principles

1. Permissive hypotension: Target SBP 80-90 mmHg (MAP ~50 mmHg) until surgical haemorrhage control (avoid in TBI/spinal injury)
2. Haemostatic resuscitation: PRBCs + FFP + Platelets in 1:1:1 ratio
3. Minimise crystalloids and colloids: Prevent dilutional coagulopathy and acidosis
4. Early tranexamic acid (TXA): Within 3 hours of injury; antifibrinolytic; especially useful given that most bleeding patients are hyperfibrinolytic
5. Warm all blood products and fluids: Prevent hypothermia

Viscoelastic Testing (VET) - Goal-Directed Therapy

• TEG (Thromboelastography) and ROTEM (Rotational Thromboelastometry)
• Provide real-time global assessment of the entire coagulation cascade
• Guide targeted component therapy (e.g., identify specific deficiency: fibrinogen, clotting factors, platelets)
• One study in trauma patients showed lower risk of death with TEG-guided transfusion vs. conventional coagulation parameters
• A 2015 systematic review could not show TEG/ROTEM superiority to standard coagulation studies; further evidence needed but increasingly adopted

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IV. COMPLICATIONS OF BLOOD TRANSFUSION (7 marks)

A. Complications of Single Transfusion

Acute Transfusion Reactions (onset: during or within 24 hours)

• TRALI: Non-cardiogenic, not volume-related, hypotension, fever, low/normal BNP, NO diuretics
• TACO: Cardiogenic, volume-related, hypertension, raised BNP, responds to diuretics, treat with non-invasive positive-pressure ventilation

Delayed Transfusion Reactions (onset: days to weeks)

• Delayed haemolytic reaction: Anamnestic antibody response; usually extravascular; haemoglobin fall 2-14 days post-transfusion; treat supportively
• Transfusion-associated GvHD (TA-GvHD): Rare but life-threatening; donor T-lymphocytes engraft and attack recipient; in immunocompromised patients or when donor is HLA-homozygous relative; fatal in >90%; prevented by irradiation of cellular products
• Post-transfusion purpura: Rare; anti-HPA-1a antibodies; severe thrombocytopaenia; treat with IVIg
• Alloimmunisation: Against RBC, HLA, or platelet antigens; leads to crossmatch difficulties and platelet refractoriness
• Iron overload: Multiple long-term transfusions (e.g., thalassaemia); each PRBC unit contains ~250 mg elemental iron; treat with chelation

Infection Transmission

• Hepatitis B, Hepatitis C, HIV, malaria, CMV, HTLV
• Bacterial infection (Yersinia enterocolitica in stored RBCs; gram-negative organisms in platelets)

B. Complications Specific to Massive Transfusion

• Hypothermia → reduces enzyme activity of coagulation cascade
• Acidosis → inhibits clotting factor function
• Coagulopathy → ongoing haemorrhage perpetuating hypothermia and acidosis

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V. MONITORING DURING MASSIVE TRANSFUSION (2 marks)

• Haemoglobin/haematocrit: Note that Hb may not reflect acute blood loss (lags behind)
• Platelet count: Maintain >50,000/μL in active bleeding (>100,000/μL if CNS/ophthalmic)
• Coagulation studies: PT, aPTT, INR, fibrinogen; target fibrinogen >1.5-2.0 g/L
• TEG / ROTEM: Real-time global coagulation; guide targeted component therapy
• Ionised calcium: Monitor and replace
• Electrolytes and ABG: K⁺, Na⁺, pH, lactate
• Temperature: Continuous; use warming measures
• Urine output: Maintain ≥1 mL/kg/hr (haemolysis monitoring, renal perfusion)
• Chest X-ray: Detect TRALI/TACO
• BNP: Raised in TACO (not TRALI)

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VI. TRANSFUSION TRIGGERS AND THRESHOLDS (2 marks)

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VII. AUTOLOGOUS BLOOD CONSERVATION STRATEGIES (1 mark)

1. Pre-operative autologous donation (PAD): Collection weeks before elective surgery
2. Acute normovolaemic haemodilution (ANH): Withdraw blood just before surgery, replace with crystalloid; retransfuse at end
3. Cell salvage (intraoperative): Suctioned blood centrifuged, washed, and reinfused; contraindicated in malignancy and bowel contamination
4. Antifibrinolytics: Tranexamic acid (TXA) - reduces blood loss and transfusion requirement; lysine analogue, inhibits plasminogen activation; 1 g IV over 10 min within 3 hours of trauma, then 1 g over 8 hours

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SUMMARY TABLE - Blood Components at a Glance

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• Colour-coded headers (dark blue section banners, mid-blue sub-sections)
• All tables formatted with alternating row colours for easy reading - blood components, transfusion reactions, TRALI vs TACO comparison, thresholds, monitoring parameters
• Bullet points for all indication/management lists
• Quick reference summary table at the end
• Source citations in the footer (Miller's, Rosen's, Bailey & Love, Tietz, Harrison's, Tintinalli's)