Revisiting Clinical Response and Refractoriness in Immune Thrombotic Thrombocytopenic Purpura

Immune thrombotic thrombocytopenic purpura (iTTP) is a rare, life-threatening condition. Caplacizumab substantially shortens the time to clinical response, yet delayed platelet count recovery is occasionally observed, raising concerns about iTTP refractoriness. This retrospective multicenter study analyzed 204 acute iTTP episodes reported to the German REACT-2020 and Austrian ATMAR registries, all treated with caplacizumab. Refractoriness was assessed using the 2017 International Working Group criteria and the more stringent definition by the French Reference Center for Thrombotic Microangiopathies. We evaluated time to platelet recovery and presence of confounding clinical conditions, potentially accounting for persistent thrombocytopenia, in all episodes. By day 5 after caplacizumab initiation, 83.8% of patients (171/204) achieved a clinical response, and the remaining 16.2% (33/204) showed at least a doubling of the platelet count. Only three patients (1.5%) met laboratory criteria for refractoriness. In all cases, plausible alternative causes were present (e.g., missed doses, infection). No patient was refractory without a confounding factor. In 8/204 patients (3.9%) we observed a markedly prolonged thrombocytopenia (≥10 days) and identified confounding conditions in all cases. In the stratified Cox model, the presence of alternative causes of thrombocytopenia was the only independent determinant of delayed platelet count normalization (HR 0.16, 95% CI 0.09-0.28, p < 0.001), whereas baseline parameters were not predictive. In the context of caplacizumab-based therapy, true refractoriness is rare. Delayed platelet count recovery is predominantly attributable to concomitant clinical conditions. Careful clinical assessment and context-sensitive interpretation of treatment response before escalating iTTP-specific therapy may avoid unnecessary treatment intensification and associated risks.

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Journal
Blood
Published
2026-02-11
DOI
https://doi.org/10.1182/blood.2025031704
Primary Topic
Complement system in diseases
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article
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article

Revisiting Clinical Response and Refractoriness in Immune Thrombotic Thrombocytopenic Purpura

Martin Nitschke, Matthias Masla, Anja Mühlfeld, Kristina Schönfelder et al.
Blood
Complement system in diseases
article

Revisiting Clinical Response and Refractoriness in Immune Thrombotic Thrombocytopenic Purpura

Martin Nitschke, Matthias Masla, Anja Mühlfeld, Kristina Schönfelder, Sadrija Cukoski, Lena Schulte‐Kemna, J. Menne, Saban Elitok, Martin Bommer, Jessica Kaufeld, Christian Pfrepper, Vedat Schwenger, Dennis A. Eichenauer, Johannes Ruhe, F Özcan, Jörn Bramstedt, C. Hart, Anja Gäckler, Evelyn Seelow, Victor Walendy, Thomas Osterholt, Petros Sirak, Anke von Bergwelt-Baildon, Felix Eisinger, Tilman Schmidt, Paul Brinkkötter, Ulf Schoenermarck, Lucas Kühne, Wolfram Johannes Jabs, Paul Knöbl, Lars Grasshoff, Wolfgang A Miesbach, Maximilian Suer, Johannes Thaler, Ralph Wendt, Linus Alexander Voelker, Marcus Brand, Felix S. Seibert
article en

Abstract

Immune thrombotic thrombocytopenic purpura (iTTP) is a rare, life-threatening condition. Caplacizumab substantially shortens the time to clinical response, yet delayed platelet count recovery is occasionally observed, raising concerns about iTTP refractoriness. This retrospective multicenter study analyzed 204 acute iTTP episodes reported to the German REACT-2020 and Austrian ATMAR registries, all treated with caplacizumab. Refractoriness was assessed using the 2017 International Working Group criteria and the more stringent definition by the French Reference Center for Thrombotic Microangiopathies. We evaluated time to platelet recovery and presence of confounding clinical conditions, potentially accounting for persistent thrombocytopenia, in all episodes. By day 5 after caplacizumab initiation, 83.8% of patients (171/204) achieved a clinical response, and the remaining 16.2% (33/204) showed at least a doubling of the platelet count. Only three patients (1.5%) met laboratory criteria for refractoriness. In all cases, plausible alternative causes were present (e.g., missed doses, infection). No patient was refractory without a confounding factor. In 8/204 patients (3.9%) we observed a markedly prolonged thrombocytopenia (≥10 days) and identified confounding conditions in all cases. In the stratified Cox model, the presence of alternative causes of thrombocytopenia was the only independent determinant of delayed platelet count normalization (HR 0.16, 95% CI 0.09-0.28, p < 0.001), whereas baseline parameters were not predictive. In the context of caplacizumab-based therapy, true refractoriness is rare. Delayed platelet count recovery is predominantly attributable to concomitant clinical conditions. Careful clinical assessment and context-sensitive interpretation of treatment response before escalating iTTP-specific therapy may avoid unnecessary treatment intensification and associated risks.

Blood
Goethe University Frankfurt (DE), MODUL University Vienna (AT), Medical University of Graz (AT), Universitätsmedizin Greifswald (DE), Klinikum St. Georg (DE), LMU Klinikum (DE), University Hospital Regensburg (DE), Medizinische Hochschule Hannover (DE), Universitätsklinik Marien Hospital Herne (DE), Augenstern (DE), Alb Fils Kliniken (DE), Deutsches Herzzentrum der Charité (DE), Klinikum Region Hannover (DE), German Society of Medical Intensive Care and Emergency Medicine (DE), Universitätsklinikum Aachen (DE), University Hospital Leipzig (DE), Klinikum Dortmund (DE), University Hospital Frankfurt (DE), Jena University Hospital (DE), Klinikum Bremerhaven-Reinkenheide (DE), Klinikum im Friedrichshain (DE), University Hospital Cologne (DE), University Hospital Ulm (DE), Klinikum Ernst von Bergmann (DE), Klinikum Stuttgart (DE), University of Duisburg-Essen (DE), Martin Luther University Halle-Wittenberg (DE), Medical University of Vienna (AT), University of Tübingen (DE), Ludwig-Maximilians-Universität München (DE), Ruhr University Bochum (DE), University of Lübeck (DE)
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Complement system in diseases
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