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

Abstract

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.