Fever, Jaundice and Acute Kidney Injury Nine Days After Transfusion
A 52-year-old woman with chronic menorrhagia and a baseline haemoglobin of 6.5 g/dL received two units of packed red cells nine days ago; the pre-transfusion antibody screen and immediate-spin cross-match were negative. She now returns with fever, jaundice, dark urine and loin pain. Results: haemoglobin 7.0 g/dL (it had risen to 9.4 g/dL on day 2), reticulocytes 6.8%, bilirubin 61 µmol/L (predominantly unconjugated), LDH 1180 U/L, haptoglobin <0.08 g/L, creatinine 165 µmol/L (baseline 82), urine dipstick positive for blood with no red cells on microscopy. The direct antiglobulin test is now positive with anti-IgG only; the eluate reacts with three Jk(a+b−) and two Jk(a+b+) reagent cells but not with two Jk(a−b+) cells; the autocontrol is negative. The transfusion service holds 14 units of red cells, none of which is phenotyped beyond ABO/D, and the surgical team wants her haemoglobin above 8 g/dL before a planned procedure.
1. Interpret the clinical and laboratory picture. What is the diagnosis, and which findings support it against the main alternatives?
Read the worked answer
The picture is a delayed haemolytic transfusion reaction (DHTR) caused by an anamnestic alloantibody against a Kidd (Jkᵃ) antigen.
Supporting evidence
- Timing: days 7–10 after transfusion is the classic window for an anamnestic secondary response.
- Serology: the eluate is specific - it reacts with Jk(a+) cells and not with Jk(a−) cells - and the negative autocontrol excludes an autoantibody. The pre-transfusion screen was negative because the antibody had fallen below detectable levels (Kidd antibodies are notoriously evanescent).
- Haemolysis biochemistry: falling haemoglobin despite transfusion, raised LDH, undetectable haptoglobin and unconjugated hyperbilirubinaemia, with reticulocytosis, indicate extravascular haemolysis.
- Renal injury: creatinine rose from 82 to 165 µmol/L with haemoglobinuria-type dipstick positivity but no red cells - consistent with haemoglobin/haem pigment nephropathy, and indicating a component of intravascular haemolysis or a severe extravascular reaction.
Alternatives considered and excluded
- Autoimmune haemolysis: negative autocontrol, no underlying lymphoma/autoimmune disease, eluate is alloantibody-specific.
- Sepsis/DIC: fever and renal injury fit, but haptoglobin is undetectable and the eluate is specific; schistocytes and thrombocytopenia were not described.
- Passenger lymphocyte syndrome: occurs after solid-organ or stem-cell transplant, not here.
- Mechanical haemolysis from a faulty giving set: would not produce a specific eluate antibody.
Kidd antibodies are complement-binding IgG and are well known for causing severe, sometimes fatal DHTRs precisely because they are missed on routine screening.
2. Set out the serological work-up you would perform now and explain what each step adds.
Read the worked answer
- Repeat ABO/D and full antibody screen on a fresh sample using LISS/column agglutination and a tube indirect antiglobulin test - Kidd antibodies may be dose-dependent, so include homozygous Jk(a+b−) cells and test by AHG with polyspecific and anti-IgG reagents.
- Repeat the DAT with anti-IgG, anti-C3d and monospecific reagents; record whether complement is present (Kidd antibodies often fix complement).
- Elution and specificity - the acid or heat eluate should be tested against a full 11-cell panel and, where available, enzyme-treated cells; document the reaction pattern with the Jk(a−) cells as the negative control.
- Phenotype or genotype the patient. Phenotyping after recent transfusion is unreliable because donor cells circulate for weeks; red-cell genotyping (or molecular Kidd typing) is preferred to establish her true Jkᵃ status and to guide future transfusion.
- Screen for additional alloantibodies - patients with one alloantibody have a substantial chance of a second; use a full phenotype or genotype profile and record it permanently.
- Exclude concurrent causes of anaemia and renal injury: blood film, coagulation screen, lactate, cultures if febrile, urinalysis for free haemoglobin.
- Lookback and haemovigilance: identify the two donor units, check whether the recipients of the co-components are affected, and file a haemovigilance report.
The specificity result must be entered on the patient's permanent record and on the laboratory information system so that any future cross-match is automatically flagged - this is the single most important step for her future safety.
3. How should the requested pre-operative transfusion be handled with the stock available? Discuss the safest strategy and the risks of the alternatives.
Read the worked answer
The request must be reframed: the risk of another haemolytic reaction now outweighs the benefit of an arbitrary haemoglobin target, so transfusion should be for symptomatic anaemia or active bleeding, not for a pre-operative number.
Preferred strategy
- Transfuse only Jk(a−) units, cross-matched by AHG. Even if the current screen appears negative on some units, Kidd antibodies can be undetectable intermittently; antigen-negative units remove that risk.
- Phenotype/genotype the patient first. If she is Jk(a−) herself, her antibody is unexpected and the specificity must be re-checked. If she is Jk(a+), record anti-Jkᵃ permanently.
- The 14 untyped units can be phenotyped rapidly (Jkᵃ antisera or molecular typing), or a local/regional donor centre can supply antigen-negative units; Kidd-negative donors are common (~23% of donors are Jk(a−)).
- Where possible, additionally match for Rh (C, c, E, e) and Kell to prevent further alloimmunisation, since she is a woman of childbearing potential.
- If surgery is elective, defer it until units are sourced and her haemoglobin is stabilised; treat iron deficiency (menorrhagia) concurrently.
Alternatives and their risks
- Transfusing unphenotyped units and hoping for the best: high risk of a second, potentially more severe reaction; the anamnestic response may already be at peak titre.
- 'Least incompatible' units: acceptable only in a life-threatening emergency, with a clinician's documented decision, divided doses, close observation and pre-medication only if there is a documented indication - not as a routine workaround.
- Blood salvage/erythropoietin/iron: adjuncts, not substitutes in acute symptomatic anaemia.
She should also receive a patient information card or alert record stating anti-Jkᵃ, and the finding should trigger a review of the pre-transfusion antibody screening sensitivity in the laboratory.