Blood Transfusion - Process And Complications
Blood transfusion is the intravenous administration of blood or blood components to restore oxygen-carrying capacity, coagulation factors, or volume, with potential complications including hemolytic reactions, febrile non-hemolytic reactions, allergic reactions, transfusion-related acute lung injury (TRALI), and transfusion-associated circulatory overload (TACO).
Blood Transfusion — Process and Complications
Blood transfusion is the intravenous administration of blood components to correct deficiencies in oxygen-carrying capacity (red cells), haemostasis (platelets, clotting factors), or plasma volume. It is one of the most common interventions in hospital medicine, but carries real risks — from fatal ABO-incompatible haemolysis to subtle iron overload in chronically transfused patients.
What a safe clinician must not miss: ABO-incompatible transfusion is the single most dangerous iatrogenic error; the majority of fatal transfusion reactions are caused by clerical/identification errors, not laboratory failures. Every step from blood-bank request to bedside administration must include patient identity verification.
The first human-to-human transfusion was performed in London 1829 by Dr Blundell, an obstetrician, for postpartum haemorrhage. [1]
These are the 8 ideas you must internalise before memorising details [1][2]:
- Different kinds of blood products — know what each contains, how it is stored, and when to use it.
- Acute adverse reactions after transfusion — recognise and manage within minutes.
- Chronic complications from transfusion — infections, iron overload.
- How to prevent complications from transfusion — specialised products, screening, bedside checks.
- Restrictive vs liberal transfusion strategy — restrictive (transfuse at Hb < 7 g/dL) is now standard of care in most settings.
- Massive transfusion protocol — know the definition ( > 10 units or 1–2× blood volume), the empirical ratio, and the metabolic complications.
- Pre-transfusion testing — ABO/RhD grouping, antibody screening, crossmatch, infectious agent screening.
- Consent and documentation — transfusion is a procedure requiring informed consent.
Blood Products — Types, Processing, Storage, and Indications
Whole blood is NOT given in Hong Kong — blood is fractionated into components. [3]
| Product | Content / Processing | Storage | Indications | Dosing / Expected Effect |
|---|---|---|---|---|
| Red Cell Concentrate (Packed Cells) | Plasma removed, replaced with CPDA-1 anticoagulant + SAGM additive; Hct ~57% | Up to 35 days at 2–6°C | Hb < 7 g/dL (general); < 8 g/dL (IHD); clinical decision | 1 unit → ↑Hb by ~1.2 g/dL and ↑Hct by 3% in a 70 kg adult; paeds: 4 mL/kg → ↑Hb ~1 g/dL [3] |
| Platelet Concentrate | 1 adult dose from 4 whole-blood donations (pooled) or single apheresis; cultured for 24h before release (high bacterial risk at RT) | 5–7 days at 20–24°C on agitator | Thrombocytopenia thresholds (see table below); platelet dysfunction + bleeding | 1 adult dose → ↑PLT by 7–10 × 10⁹/L [3] |
| Fresh Frozen Plasma (FFP) | 150–300 mL; all soluble plasma proteins and clotting factors | Up to 2 years at −30°C | TTP (plasma exchange); massive transfusion; warfarin reversal with bleeding; PT/aPTT > 1.5× control + bleeding/procedure | 2–4 units adults; 12–15 mL/kg paeds [3] |
| Cryoprecipitate | Controlled thawing of FFP → precipitate rich in fibrinogen (150–300 mg), F8 (80–120 U), vWF; 20–50 mL/unit | Frozen | Fibrinogen < 1 g/L; vWD (if DDAVP/factor concentrate not suitable); F13 deficiency | 10 U/dose adults (raises fibrinogen ~1 g/L) [3] |
| White Cell Concentrate (Buffy Coat) | Pooled or apheresis; must be irradiated | RT for max 24h — must pre-arrange with HKRCBTS | Neutropenia ( < 0.5 × 10⁹/L) + documented infection unresponsive to broad-spectrum Abx + antifungals ≥48h | 10 U/day for ≥4 days [3] |
| Product | Indication |
|---|---|
| Human albumin | Volume expansion, hypoalbuminaemia |
| Clotting factor concentrate | Haemophilia A/B, specific factor deficiencies |
| Intravenous immunoglobulin (IVIg) | ITP, Kawasaki, immunodeficiency, GBS |
| Prothrombin complex concentrate (PCC) — 3-factor (II, IX, X) or 4-factor (II, VII, IX, X) | Similar to FFP but for torrential bleeding / ICH; provides ↑factors in ↓volume; risk: thrombosis [3] |
| Platelet Count | Setting |
|---|---|
| < 10 × 10⁹/L | Stable patients (except ITP, SLE, TTP, HUS) |
| < 20 × 10⁹/L | Fever / sepsis |
| < 50 × 10⁹/L | Major/mucosal bleeding; before invasive procedures; stable premature neonates |
| < 100 × 10⁹/L | CNS/retinal bleeding or surgery; post-cardiopulmonary bypass active bleeding; sick premature neonates |
This table is very high yield — it links product processing to the specific complication it prevents [3]:
| Product | Processing | Purpose | Indications |
|---|---|---|---|
| Leukodepleted blood | Pre-storage buffy-coat removal OR post-storage in-line leukocyte filter | Prevent FNHTR, HLA alloimmunisation, CMV transmission | Transfusion-dependent thalassaemia; haematological diseases; ≥2 severe FNHTR episodes; paed oncology [1][3][7] |
| Irradiated cellular components | 2500 cGy irradiation before transfusion | Inactivates donor lymphocytes → prevents TA-GVHD (otherwise 100% fatal) | Intrauterine transfusion; SCID; HSCT recipients; Hodgkin disease; purine analogue chemo; transfusion from 1° relatives [3] |
| CMV-seronegative components | Tested seronegative for CMV (not routine) | Prevent CMV transmission in immunocompromised | CMV-negative pregnant women; CMV-negative allo-HSCT recipients; intrauterine transfusion; HIV [3] |
| Rh(D)-negative red cells | Tested Rh(D) negative | Prevent Rh-haemolytic reaction / Rh(D) sensitisation in women of childbearing age | HDN due to anti-D; RhD-neg with anti-D; RhD-neg female before menopause; emergency resuscitation of Caucasian female with unknown RhD [3] |
Thalassaemia Transfusion
For thalassaemia major, use leukodepleted packed cells to ↓FNHTR and TRALI. Target: pre-transfusion Hb 9–10 g/dL, post-transfusion Hb ~14 g/dL. Frequency: every 4 weeks. Hyper-transfusion suppresses ineffective erythropoiesis and ↓GI iron absorption. [7]
The restrictive transfusion strategy (transfuse when Hb < 7 g/dL, aim 7–9 g/dL) is now standard in most clinical scenarios. [4][5]
| Clinical Setting | Transfusion Threshold | Target Hb | Rationale |
|---|---|---|---|
| General | Hb < 7 g/dL | 7–9 g/dL | Large RCT evidence: restrictive strategy ↓mortality at 6 weeks [4] |
| Acute variceal bleeding (cirrhosis) | Hb < 7 g/dL | 7–9 g/dL | Liberal transfusion engorges vasculature → ↑portal pressure → ↑rebleeding [4][5] |
| ACS / cardiovascular disease | Hb < 8 g/dL (consider 8–10 g/dL) | ≥8–9 g/dL | Avoid triggering adverse vascular events [4] |
| Haemodynamically unstable | Transfuse liberally | Guided by clinical response | Exceptions to restrictive strategy [4] |
| Critical care / HF / shock | Hb < 7–8 g/dL | 7–9 g/dL | Generally still restrict [3] |
| Thalassaemia major | Pre-transfusion Hb < 9–10 g/dL | Post-transfusion 14 g/dL | Suppress ineffective erythropoiesis [7] |
Exam Trap
Do NOT confuse the thresholds. The two exceptions to restrictive transfusion in UGIB are: (1) haemodynamically unstable patients and (2) underlying cardiovascular disease (especially ACS) — in these, transfuse more liberally. [4]
Key Steps Explained
- Consent: Explain risks (fever, allergy, infection, serious but rare reactions). Document.
- Pre-transfusion testing: ABO/RhD compatibility + infectious agent tests (HBV, HCV, HIV, syphilis) — done at HKRCBTS [3].
- Bedside check: The most critical safety step. Two staff independently verify patient identity against the blood unit label and compatibility form.
- Monitoring during transfusion: Baseline vitals → 15 min after start → then at least hourly. Most severe reactions occur within the first 15 minutes.
- Unit-by-unit transfusion is now preferred: Reassess Hb after each unit — often 1 unit is sufficient. Traditional 2-unit ordering is outdated. [3]
Complications of Blood Transfusion
| Timing | Immune-Mediated | Non-Immune-Mediated |
|---|---|---|
| Acute (< 24h) | AHTR, FNHTR, allergic/anaphylaxis, TRALI | Bacterial contamination, TACO, air embolism, primary hypotensive reaction |
| Delayed | DHTR, TA-GVHD, post-transfusion purpura, HLA alloimmunisation | Infections (viral, parasitic, prion), iron overload (haemosiderosis) |
| Massive transfusion specific | — | Hypothermia, coagulopathy, hyperkalaemia, citrate toxicity (↓Ca²⁺), metabolic alkalosis |
Acute Complications (< 24 hours)
The most common symptoms reported in acute transfusion reactions are: fever, chills, pruritus, urticaria. [1]
- Incidence: ~3% (commonest reaction) [6]
- Pathogenesis: HLA Class I antigens are carried in high concentrations by leucocytes and platelets → reaction with patient's HLA antibodies → cytokine release from stored WBCs [8][9]
- S/S: Temperature rise ≥1°C, chills/rigors during or shortly after transfusion; patient otherwise well
- Management:
- Prevention: Leukodepleted blood products [3][8]
Key Distinction
Fever during transfusion ≠ automatic stop. You MUST exclude the dangerous causes (ABO incompatibility, bacterial contamination) first, but if it's FNHTR → treat symptomatically and continue. If it was ABO incompatibility or bacterial contamination → stop immediately. [1]
- Incidence: ~1/6,000 [6]
- Pathogenesis: ABO-incompatible red cells → pre-formed IgM anti-A or anti-B activate complement → intravascular haemolysis → DIC → renal failure
- S/S: Within minutes of starting transfusion — fever, rigors, back/loin pain, chest tightness, hypotension, dark urine (haemoglobinuria), DIC
- Management:
- STOP transfusion immediately — do NOT restart
- Keep IV line open with NS
- Resuscitate: fluids, vasopressors if needed
- Send: blood unit + IV set to lab; repeat group/crossmatch; direct antiglobulin test (DAT); serum for free Hb, haptoglobin, bilirubin, LDH; urine for haemoglobin
- Monitor urine output (Foley's catheter) — maintain > 100 mL/h to prevent acute renal failure
- Manage DIC if it develops (FFP, cryoprecipitate, platelets)
- Report to blood bank and HKRCBTS
- Root cause: Almost always a clerical error — wrong patient, wrong label, wrong unit
- Urticaria: ~1% incidence [6]; localised hives/itch; due to reaction to donor plasma proteins
- Mx: Antihistamines; can often continue transfusion after symptoms settle
- Anaphylaxis: ~1/150,000 [6]; generalised urticaria, bronchospasm, hypotension, laryngeal oedema
- Classically in IgA-deficient patients with anti-IgA antibodies reacting to donor IgA
- Mx: STOP transfusion; IM adrenaline; ABC approach; IV fluids; future: use washed blood products or IgA-deficient donor products
- Incidence: < 1/10,000 [6]
- Pathogenesis: Donor's HLA Class I and/or II antibodies form immune complexes with corresponding HLA antigens of the patient → deposition on lung tissue → non-cardiogenic pulmonary oedema [8][9]
- S/S: Acute respiratory distress, bilateral pulmonary infiltrates, hypoxia within 6h of transfusion; NO evidence of circulatory overload (normal CVP)
- Dx: Clinical; CXR bilateral infiltrates; normal CVP (differentiates from TACO)
- Mx: Supportive — O₂, ventilation if needed; usually resolves within 48–72h
- Prevention: Leukodepleted products; avoid plasma from multiparous female donors (who have higher rates of HLA antibodies)
TRALI vs TACO differentiation is a classic exam question:
- TRALI: normal/low CVP, non-cardiogenic pulmonary oedema, onset < 6h
- TACO: ↑CVP with pulmonary oedema, onset 6–12h, responds to diuretics [3]
- Incidence: 0.2/10⁶ units for RBCs, 10/10⁶ units for platelets (50× higher risk for platelets) [3]
- Pathogenesis:
- S/S: Rapid onset of chills/rigors, high fever (usually > 2°C rise), N/V/D, hypotension — can mimic AHTR with DIC, intravascular haemolysis, renal failure [3]
- Management:
- STOP transfusion, change set, keep IV open with NS
- Urgent Gram stain of implicated unit
- Blood cultures from patient AND unit
- Broad-spectrum antibiotics with adequate anti-pseudomonal coverage
- Monitor for septic shock (vitals, I/O)
- Report to HKRCBTS [3]
- Incidence: 1/10,000 [3]
- Pathogenesis: Volume overload from any blood component; risk factors: pre-existing HF, CKD, elderly
- S/S: Respiratory distress (SOB, orthopnoea) in 6–12h of completing transfusion
- Dx: ↑CVP with pulmonary oedema (differentiates from TRALI) [3]
- Mx: O₂, diuretics ± ventilation; slow transfusion rate in future
Delayed Complications
- Onset: 3–14 days post-transfusion
- Pathogenesis: Anamnestic antibody response to minor red cell antigens (e.g. Kidd, Duffy, Kell); prior sensitisation from transfusion or pregnancy
- S/S: Falling Hb despite transfusion, mild jaundice, positive DAT
- Mx: Usually self-limiting; identify antibody for future transfusions
- Pathogenesis: Immunocompetent donor lymphocytes engraft in immunocompromised recipient → mount immune attack on host BM, skin, liver, GI
- S/S: Profound BM suppression, rash, liver dysfunction, diarrhoea → virtually 100% fatal [3]
- Prevention: Irradiated cellular components (2500 cGy) — indications listed above [3]
- Rare; thrombocytopenia 5–10 days post-transfusion due to anti-platelet antibodies (usually anti-HPA-1a)
- Mx: IVIg; future: HPA-1a-negative platelets
Risk of infections is not negligible as screening is not always accurate. [3]
| Agent | Estimated Risk | Notes |
|---|---|---|
| HBV | 1:3,000–1:10,000 | Most common transfusion-transmitted viral infection in HK [3][6] |
| HCV | 1:300,000 | [3] |
| HIV 1/2 | < 1:1,000,000 | [3] |
| CMV | Common; 40% adults seropositive | Serious in immunocompromised; prevented by leukodepletion or CMV-seronegative products [3] |
| HTLV-1 | Rare | Causes adult T-cell leukaemia/lymphoma or tropical spastic paraparesis [3] |
| Human parvovirus B19 | 1:10,000 | Aplastic crisis in chronic haemolysis [3] |
| Bacterial | See above | Yersinia, Pseudomonas (cold-resistant); skin flora [3] |
| Malaria (Plasmodium spp) | Rare in HK | Screened by travel history [3][6] |
| Trypanosoma cruzi | Rare | Chagas disease [3] |
| Prion (vCJD) | Cannot be screened | PrP mainly on B-lymphoid cells; infectivity: WBC > plasma > albumin [3] |
| Treponema pallidum | Rare | Serology not accurate enough [3] |
Measures to decrease risk of transfusion-related infections [3]:
- Donor screening questionnaire (travel, risk behaviours)
- Serological and NAT (nucleic acid testing) for HBV, HCV, HIV, syphilis
- Bacterial culture of platelet units (24h)
- Leukodepletion (↓CMV, HTLV-1)
- Pathogen inactivation (methylene blue for paediatric FFP in HK)
Massive transfusion = transfusion of > 10 units (or 1–2× patient's blood volume) [2][6]
Indications: severe trauma, ruptured AAA, obstetric haemorrhage [6]
Empirical ratio: packed cells : FFP : platelets = 1:1:1 (with repeated blood sampling for Hb, clotting profile) [6]
| Complication | Mechanism | Key Detail |
|---|---|---|
| Hypothermia | Each unit at 4°C → requires 1255 kJ to warm to 37°C | Use blood warmer for massive transfusion [2] |
| Coagulopathy | Haemodilution of clotting factors; Factor V and VIII decline quickly within 24h after collection | Replace with FFP, cryoprecipitate [2] |
| Hyperkalaemia | K⁺ leaks from stored RBCs (40–70 mmol/L in stored blood); older units worse | Monitor K⁺; use ECG monitoring [2][6] |
| Citrate toxicity → Hypocalcaemia | Citrate anticoagulant chelates Ca²⁺ → ↓ionised Ca²⁺ → cardiac dysfunction | Give IV calcium gluconate [2][6] |
| Metabolic alkalosis | Citrate and lactate in stored blood are metabolised to HCO₃⁻ | Paradoxical: initial acidosis from citrate/lactate, then delayed alkalosis [6] |
| 2,3-DPG degradation | Stored blood has ↓2,3-DPG → left-shifted O₂ dissociation curve → ↓O₂ delivery to tissues | [2] |
| Immunomodulation | ↑ratio of suppressor to helper T-cells → ↑infection risk | Relevant in cancer surgery — transfusion-related immunosuppression → ↑recurrence risk [2][6] |
Massive Transfusion Mnemonic: 'CHICK-M'
Coagulopathy, Hypothermia, hyperK (Ion), Citrate toxicity (hypoCa²⁺), K (metabolic alKalosis), M (immunoModulation / 2,3-DPG)
Iron Overload (Haemosiderosis)
- Each 500 mL blood contains ~250 mg iron = 8 months' worth of dietary iron [10]
- Body has no good mechanism for iron excretion → chronic transfusion → iron overload → toxic to the heart (cardiomyopathy), liver (cirrhosis), endocrine (diabetes, hypogonadism) [10]
- Management: Iron chelation — Desferrioxamine (DFO), Deferiprone (DFP), Deferasirox → bind iron, excrete via urine and faeces [10]
- Critical in thalassaemia major patients on regular transfusion
Special Situations and Modifications
- Transfusion causes immunosuppression → ↑risk of recurrence → higher threshold / avoid transfusion if possible after curative cancer surgery [6]
- Blood transfusion causes falsely low HbA1c (new donor RBCs not yet glycosylated) — important to remember when monitoring diabetic patients who have been recently transfused [11]
Exam Approach
- Expect scenarios: "Patient develops fever 30 min into transfusion — what is the most likely diagnosis and management?"
- Know the differentiation table: FNHTR vs AHTR vs bacterial contamination vs TRALI vs TACO
- Know platelet transfusion thresholds by clinical setting
- Know massive transfusion complications and the 1:1:1 ratio
- Know specialised products and which complication each prevents
- Bedside management of acute transfusion reaction (stepwise protocol)
- Counselling patient about need for transfusion — explain risks in lay terms
- Prescribing blood products: "I would prescribe 1 unit of leukodepleted packed red cells to be transfused over 2–4 hours with vital sign monitoring at baseline, 15 minutes, and then hourly"
- Assuming all fever = stop transfusion (FNHTR → can continue)
- Forgetting to check patient identity at bedside
- Confusing TRALI (normal CVP) with TACO (raised CVP)
- Not knowing that platelets have 50× higher bacterial contamination risk than RBCs
- Forgetting citrate toxicity → hypocalcaemia in massive transfusion
High Yield Summary
- Blood components in HK: packed cells, platelets, FFP, cryoprecipitate, buffy coat; whole blood is NOT used [3]
- Restrictive transfusion (Hb < 7 g/dL) is standard; exceptions: ACS (< 8), haemodynamically unstable (liberal) [4][6]
- Most common acute reaction: FNHTR — give paracetamol, continue transfusion after excluding serious causes [1]
- Most dangerous: AHTR from ABO incompatibility — almost always a clerical error [3]
- TRALI: donor HLA antibodies + recipient HLA antigens → lung immune complex deposition → normal CVP [8][9]
- TACO: volume overload → ↑CVP → diuretics [3]
- Bacterial contamination: platelets >> RBCs; cold-resistant organisms: Yersinia, Pseudomonas [3]
- Massive transfusion ( > 10 units): 1:1:1 ratio; complications = hypothermia, coagulopathy, hyperK⁺, citrate toxicity (↓Ca²⁺), metabolic alkalosis [2][6]
- Specialised products: leukodepleted (↓FNHTR/TRALI), irradiated (↓TA-GVHD — 100% fatal if missed), CMV-negative, RhD-negative [3]
- Iron overload in chronic transfusion: 250 mg Fe per unit; chelation with DFO/DFP/Deferasirox [10]
Active Recall - Blood Transfusion
[1] Senior notes: Block A - Fever after a blood transfusion_ transfusion and related problems.pdf [2] GC lecture slides: GC 188. Hit by a van, in shock with internal bleeding Abdominal injury.pdf (p26) [3] Senior notes: Ryan Ho Haemtology.pdf (pp142–151) [4] Senior notes: Block A - Coffee ground vomitus tarry stool upper GI bleeding.pdf (pp13–14) [5] Senior notes: Block A - Abdominal distension_ ascites and cirrhosis.pdf (p8) [6] GC lecture slides / CFB lecture slides: CFB 22_WCS FLUID ELECTROLYTES TRANSFUSION_r20240814.pdf (pp25, 32); Ryan Ho Critical Care.pdf (p20) [7] Senior notes: Adrian Lui Pediatrics Notes.pdf (p366) [8] Lecture slides: Laboratory Diagnostic Investigations Seminar_Tissue typing and transplant immunology_2025 - Dr J Kwok.pdf (pp131–132) [9] GC lecture slides: GC 049. Fever after a blood transfusion.pdf (pp1–2) [10] Senior notes: Block A - Hematology Interactive Tutorial.pdf (p5) [11] Senior notes: Block A - Polyuria and polydipsia_ glucose metabolism; diabetes mellitus; diabetic ketoacidosis.pdf (p4)
Waldenström Macroglobulinaemia
Waldenström macroglobulinaemia is a lymphoplasmacytic lymphoma characterized by clonal proliferation of B lymphocytes in the bone marrow with overproduction of monoclonal immunoglobulin M (IgM), leading to hyperviscosity and cytopenias.
Immune Thrombocytopenia (ITP)
Immune thrombocytopenia is an autoimmune disorder characterized by antibody-mediated platelet destruction and impaired platelet production, resulting in isolated thrombocytopenia and increased bleeding risk.