Ceftriaxone-associated immune haemolytic anaemia: A patient-level systematic review

Ceftriaxone can cause acute haemolysis. Its clinical presentation, risk factors, and outcomes remain incompletely characterized. We conducted a systematic review of published cases with patient-level data, following international guidelines and with registration in PROSPERO (CRD420261338709). Reports were identified through three bibliographic databases. Only cases meeting a predefined reporting completeness threshold were included. Clinical features, laboratory findings, management strategies, and outcomes were analysed, with prespecified comparisons between paediatric and adult patients. Eighty-nine reports describing 101 patients were included: 57% were aged ≤18 years and 53% were male. Acute kidney injury and disseminated intravascular coagulation were reported in 23% and 13% of patients, respectively. Overall mortality was 24%. Mortality was not associated with sex, age group, preexisting haematological conditions, or acute kidney injury, but was significantly higher among patients with disseminated intravascular coagulation. Mortality declined markedly from 80% among cases reported between 1991 and 2000 to 18% among those reported thereafter. A direct antiglobulin test was performed in 89% of cases and was positive in 93%. Among characterized positive tests, complement deposition was present in 90%, either alone (53%) or combined with immunoglobulin G (37%). Management primarily consisted of ceftriaxone discontinuation. Red blood cell transfusions were administered in 67% of cases, corticosteroids in 45%, and polyclonal immunoglobulins in 16%. Ceftriaxone-associated haemolytic anaemia is generally associated with a positive direct antiglobulin test and carries a substantial risk of rapid fatal deterioration. Given its abrupt presentation, a high index of suspicion, early recognition, and prompt discontinuation of ceftriaxone are critical.