2025 focused update of the 2020 ISTH guidelines for management of thrombotic thrombocytopenic purpura

Background: Over the past few years, new information has emerged in the management of both immune thrombotic thrombocytopenic purpura (iTTP) and congenital (or hereditary) thrombotic thrombocytopenic purpura (cTTP). Methods: In March 2024, the International Society on Thrombosis and Haemostasis (ISTH) formed a multidisciplinary panel comprising hematologists, intensivists, nephrologists, pathologists, patient representatives, and a methodology team. The panel discussed all treatment questions related to thrombotic thrombocytopenic purpura (TTP) using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) method to appraise evidence and formulate recommendations. Results: For patients with cTTP in remission, a new strong recommendation was issued for the use of recombinant ADAMTS-13 over fresh frozen plasma in the context of moderate certainty evidence. The panel also revised a previous recommendation and suggested using fresh frozen plasma over a watch-and-wait approach for patients with cTTP in remission based on very low certainty evidence should recombinant. The panel reviewed and referenced new publications supporting therapeutic efficacy, potential survival benefit, and cost considerations of adding caplacizumab to therapeutic plasma exchange, corticosteroids, and rituximab, but concluded that no change was warranted to the previous recommendations in the management of iTTP. Good practice statements on the concomitant use of antithrombotic agents were marginally modified. Conclusions: For patients with iTTP, no change to 2020's recommendations. For patients with cTTP, the panel supports ADAMTS-13 replacement. Where accessible, recombinant ADAMTS-13 provides the most favorable balance of benefits and risks. Otherwise, fresh frozen plasma may still be effective. Shared decision-making should include the benefits, the potential harms, and the burden of care. (International Society on Thrombosis and Haemostasis)