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PA21.1-6 | Transfusion Reactions & Investigation — Part 3
Delayed Transfusion Reactions
Delayed Transfusion Reactions
1. Delayed Haemolytic Transfusion Reaction (DHTR)
Occurs 2–14 days post-transfusion. Mechanism: an anamnestic (secondary) immune response — the patient was sensitised to a red cell antigen (most commonly Rh, Kidd, Duffy, Kell systems) by a previous transfusion or pregnancy. Titre was too low to detect pre-transfusion; re-exposure boosts IgG antibody production.
Mechanism: IgG-coated donor cells are removed by splenic macrophages — extravascular haemolysis (less catastrophic than AHTR).
Features: Falling Hb, mild jaundice, low-grade fever, positive DAT. Usually self-limiting. Detect with post-transfusion DAT and antibody screen.
2. Transfusion-Associated Graft-versus-Host Disease (TA-GVHD)
Occurs 1–6 weeks post-transfusion in severely immunocompromised patients (haematological malignancies, bone marrow transplant, congenital immunodeficiency).
Mechanism: Viable donor T-lymphocytes engraft and mount a GvH attack against host tissues.
Features: Fever, rash, diarrhoea, hepatitis, pancytopenia (marrow aplasia) — mortality >90%.
Prevention: Gamma-irradiation of cellular blood products kills donor lymphocytes. Leukoreduction alone is NOT sufficient.
3. Iron Overload
Each unit of blood contains ~200 mg elemental iron. Patients receiving chronic transfusions (e.g., thalassaemia, sickle cell disease) accumulate iron in the liver, heart, and endocrine organs — haemosiderosis → cirrhosis, cardiomyopathy, diabetes.
Treatment: Iron chelation therapy (desferrioxamine, deferasirox).
4. Post-Transfusion Purpura (PTP)
Rare. Occurs ~7–10 days post-transfusion. Antibody (usually anti-HPA-1a) destroys both donor AND recipient platelets → severe thrombocytopenia → purpura, bleeding.
Extravascular vs Intravascular Haemolysis: Mechanisms and Clinical Features
CLINICAL PEARL
TA-GVHD vs AHTR — the overlooked danger:
Both can be fatal, but TA-GVHD is uniquely silent in its early phase and is virtually 100% preventable with irradiation. The clinical pearl: always check for immunocompromise before ordering blood products. A patient on aggressive chemotherapy, a post-BMT recipient, or a premature neonate — these patients MUST receive irradiated (and often CMV-negative, leukodepleted) products. Asking 'is this patient immunocompromised?' before every transfusion costs nothing; missing it costs everything.
Investigation of a Suspected Transfusion Reaction
Investigation of a Suspected Transfusion Reaction
PA21.4 specifically requires you to enumerate the investigation steps — meaning an ordered, actionable sequence. Memorise the following algorithm:
Step 1 — STOP the transfusion immediately.
Do not wait to confirm — suspicion alone is sufficient to stop.
Step 2 — Maintain IV access; assess and stabilise the patient.
Check: airway, breathing, circulation. Record vital signs. Do NOT remove the cannula — you need access for resuscitation and fresh samples.
Step 3 — Clerical recheck.
Verify the patient's wristband and blood group vs the unit label, request form, and compatibility report. Most AHTR are caused by clerical error — this step is both investigative and immediately diagnostic.
Step 4 — Return the unit + giving set + all labels to the blood bank.
Do NOT discard anything. The blood bank will re-examine the unit for haemolysis, repeat typing, and perform direct gram stain and culture.
Step 5 — Collect fresh samples from the patient (from a different vein).
• Clotted sample: repeat ABO/Rh grouping, repeat crossmatch, serum for haemolysis
• EDTA sample: direct antiglobulin test (DAT)
• Pre-transfusion sample (from the blood bank archive): repeat DAT and grouping
Step 6 — Check for evidence of haemolysis.
• Visual inspection of plasma: pink/red = haemoglobinaemia
• Urine dipstick + microscopy: haemoglobinuria (haem-positive, no RBCs on microscopy)
• Serum LDH, bilirubin, free Hb: all elevated in haemolysis
• Haptoglobin: decreased (binds free Hb)
Step 7 — Blood culture.
One set from the patient + one from the blood unit residue (for septic reaction).
Step 8 — Monitor renal function and coagulation.
• Urine output, creatinine, urea — renal failure in AHTR
• Prothrombin time, aPTT, fibrinogen, D-dimer — DIC in AHTR
Stepwise Investigation Protocol for Transfusion Reactions
SELF-CHECK
After stopping a suspected acute haemolytic transfusion reaction, what is the SINGLE MOST IMPORTANT immediate clerical action that is simultaneously investigative and preventive of further harm?
A. Send the patient's urine for haemoglobin dipstick
B. Order an urgent complete blood count
C. Verify the patient's identity band and blood group against the unit label and compatibility report
D. Collect blood for direct antiglobulin test (DAT)
Reveal Answer
Answer: C. Verify the patient's identity band and blood group against the unit label and compatibility report
The majority of AHTRs result from clerical error — a mismatch between the patient's identity and the unit issued. Rechecking the patient's wristband against the unit label and crossmatch report is the immediate clerical action that identifies whether a clerical error occurred AND prevents further transfusion of the wrong unit to any patient. Urine haemoglobin (A) and DAT (D) are important laboratory steps but come after stopping and stabilising. CBC (B) is useful for trend monitoring but is not the most urgent single action.
Prevention — the Bedside Imperative
Preventing Fatal Transfusion Reactions at the Bedside
The majority of ABO haemolytic deaths are preventable. The bedside pre-transfusion check is a non-delegable clinical duty:
- Two-identifier rule: Confirm patient name + date of birth (or hospital number) on the wristband — NOT from memory or a chart.
- Unit label check: Donor group and compatibility label must match the patient's group.
- Expiry and integrity: Inspect the unit for discolouration, clots, or bag leaks — signs of bacterial contamination.
- Right patient, right time: Transfuse one unit at a time; do not switch units mid-transfusion without re-checking.
A 10-second bedside check before every unit is the single most powerful intervention to prevent the most fatal transfusion reaction. No technology substitutes for this.
Additional system-level prevention strategies:
| Reaction | Prevention |
|---|---|
| AHTR | Strict ABO/Rh pre-transfusion verification |
| FNHTR | Leucoreduction |
| TRALI | Defer high-risk donors (multiparous women with anti-HLA antibodies) |
| TACO | Slow transfusion; loop diuretic in at-risk patients |
| TA-GVHD | Gamma-irradiation of cellular products |
| Iron overload | Iron chelation in chronic transfusion patients |
| Septic | Bacterial screening of units; good collection technique |
SELF-CHECK
A 7-year-old boy with acute lymphoblastic leukaemia receiving induction chemotherapy requires a packed red cell transfusion. Which special preparation of the blood product is MANDATORY to prevent a potentially fatal complication?
A. Washed red cells to prevent IgA-mediated anaphylaxis
B. Gamma-irradiated blood to prevent transfusion-associated graft-versus-host disease
C. CMV-negative blood only
D. ABO-matched platelets to prevent post-transfusion purpura
Reveal Answer
Answer: B. Gamma-irradiated blood to prevent transfusion-associated graft-versus-host disease
Severely immunocompromised patients — including those on intensive chemotherapy — cannot destroy viable donor T-lymphocytes. These T-cells engraft and attack host tissues, causing TA-GVHD with >90% mortality. Gamma-irradiation kills donor lymphocytes and is mandatory for all cellular products given to immunocompromised patients. Washed red cells (A) are indicated for IgA-deficient patients. CMV-negative blood (C) is also recommended for immunocompromised patients and transplant recipients but does not prevent TA-GVHD. Platelet matching (D) does not prevent TA-GVHD.