Subacute immune-mediated thrombotic thrombocytopenic purpura: prolonged prodromes and delayed diagnosis in 5 cases

Immune thrombotic thrombocytopenic purpura (iTTP) is caused by a deficiency in ADAMTS-13 activity and is classically an acute-onset disorder. A subset of patients, however, may experience a more insidious course. Comprehensive reports of these presentations are sparse, and delayed diagnosis has been associated with increased thrombotic complications and mortality.

To report on 5 cases of subacute iTTP presentations involving a prolonged prodromal period of nonspecific symptoms with gradual decline in platelet counts before acute deterioration and subsequent diagnosis.

This retrospective case series identified delayed iTTP diagnoses in 5 patients with thrombocytopenia (platelets <150 ×10⁹/L) and ADAMTS-13 activity <10 IU/dL managed at a single UK specialist tertiary referral center between 2022 and 2024. Clinical data, laboratory results, treatments, and outcomes were obtained from medical records.

The median age was 52 years (range, 3-78), and 3 patients were female. Median time from first nonspecific symptom to diagnosis was 84 days (range, 60-120), compared with 22 days (range, 5-65) from the first documented evidence of microangiopathic hemolytic anemia or thrombotic microangiopathy. All patients were found to have severe thrombocytopenia and ADAMTS-13 activity <10 IU/dL, with 3 showing anti-ADAMTS-13 IgG positivity. All patients were treated with plasma exchange, corticosteroids, rituximab, and caplacizumab; 3 required obinutuzumab for relapsed/refractory low ADAMTS-13 levels.

Insidious changes to blood count trends and prodromal symptoms risk being overlooked, delaying treatment and increasing morbidity and mortality. Broader awareness of subacute iTTP presentations outside hematology may improve timely diagnosis and management.