The cornerstone of life-saving therapy in immune-mediated thrombotic thrombocytopenic purpura (iTTP) has been plasma exchange (PEX) combined with immunomodulatory strategies. Caplacizumab, a novel anti–von Willebrand factor nanobody trialed in 2 multicenter randomized controlled trials (RCTs) leading to European Union and US Food and Drug Administration approval, has been available in the United Kingdom (UK) through a patient access scheme. Data were collected retrospectively from 2018 to 2020 for 85 patients (4 children) receiving caplacizumab from 22 UK hospitals. Patient characteristics and outcomes in the real-world clinical setting were compared with caplacizumab trial end points and historical outcomes in the precaplacizumab era. Eighty-four of 85 patients received steroid and rituximab alongside PEX; 26% required intubation. Median time to platelet count normalization (3 days), duration of PEX (7 days), and hospital stay (12 days) were comparable with RCT data. Median duration of PEX and time from PEX initiation to platelet count normalization were favorable compared with historical outcomes (P < .05). Thrombotic thrombocytopenic purpura (TTP) recurred in 5 of 85 patients; all had persistent ADAMTS13 activity < 5 IU/dL. Of 31 adverse events in 26 patients, 17 of 31 (55%) were bleeding episodes, and 5 of 31 (16%) were thrombotic events (2 unrelated to caplacizumab); mortality was 6% (5/85), with no deaths attributed to caplacizumab. In 4 of 5 deaths, caplacizumab was introduced >48 hours after PEX initiation (3-21 days). This real-world evidence represents the first and largest series of TTP patients, including pediatric patients, receiving caplacizumab outside of clinical trials. Representative of true clinical practice, the findings provide valuable information for clinicians treating TTP globally.

We noted anaphylaxis in a patient with thrombotic thrombocytopenic purpura (TTP), which was associated with human antichimeric antibodies (HACA) to rituximab. Because of the high risk of relapse of TTP, further elective therapy was preferred. Treatment with ofatumumab, a human monoclonal anti-CD20 antibody, was successfully completed, with no reactions and with normalization of ADAMTS13 activity.

Direct oral anticoagulants (DOACs) are increasingly used for the treatment of thrombosis. While inhibitors of factor IIa and factor Xa have shown effectiveness, the risk of bleeding remains a significant concern. Recently, direct factor XIa inhibitors—including asundexian and milvexian—have emerged as potential anticoagulation therapies, based on clinical observations that patients with factor XIa deficiencies seldom present with spontaneous bleeding tendencies. The interferences associated with DOACs in routine and specialised coagulation assays are well-described; however, the interferences associated with emerging FXIa inhibitors are largely uncharacterised. Here, we briefly report the impact of asundexian and milvexian in routine coagulation assays using in vitro plasma-based systems. Asundexian and milvexian induce concentration-dependent prolongations in APTT-based assays with curvilinear regressions, which may be suitable for the measurement of pharmacodynamic effects at peak levels ex vivo. We also report differential sensitivities of APTT-based assays—particularly at higher FXIa inhibitor concentrations—highlighting the clinical need for an extensive evaluation of interferences associated with FXIa inhibitors in coagulation assays.

Direct inhibition of factor (F)XI/FXIa is emerging as a promising anticoagulant strategy to mitigate the risk of bleeding typically associated with antithrombotic medications, including direct oral anticoagulants (DOACs). While DOACs are known to interfere with a broad range of coagulation assays, the interferences associated with emerging FXIa inhibitors remain incompletely characterized. This study evaluated the interferences associated with the FXIa inhibitors asundexian and milvexian in a panel of routine and specialized coagulation assays. Additionally, we assessed the capacity of charcoal-based adsorbents-including raw activated charcoal and DOAC-Stop-to remove interferences in coagulometric assays. Human-derived plasma was anticoagulated with increasing concentrations of asundexian or milvexian (0-10 000 ng/mL) and assayed for routine and specialized coagulation parameters before and after treatment with charcoal-based adsorbents using Sysmex CN/CS-series analyzers. Plasma was anticoagulated with both asundexian and milvexian at therapeutic and supratherapeutic concentrations representative of those reported in recent pharmacokinetic trials. Asundexian and milvexian produced significant dose-dependent interferences in FXIa-dependent coagulation assays, including markedly prolonged activated partial thromboplastin time-based clotting times and markedly reduced intrinsic coagulation factor activities. Treatment with charcoal-based adsorbents effectively removed both asundexian- and milvexian-associated interferences across all affected assays. Emerging FXIa inhibitors interfere significantly with FXIa-dependent coagulation assays, potentially leading to misinterpretation of hemostatic function. However, charcoal-based adsorbents efficiently remove these interferences and enable routine and specialized coagulation testing in the presence of asundexian and milvexian.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to an unprecedented global healthcare crisis. While SARS-CoV-2-associated COVID-19 affects primarily the respiratory system, patients with COVID-19 frequently develop extrapulmonary manifestations. Notably, changes in the hematological system, including lymphocytopenia, neutrophilia and significant abnormalities of hemostatic markers, were observed early in the pandemic. Hematological manifestations have since been recognized as important parameters in the pathophysiology of SARS-CoV-2 and in the management of patients with COVID-19. In this narrative review, we summarize the state-of-the-art regarding the hematological and hemostatic abnormalities observed in patients with SARS-CoV-2-associated COVID-19, as well as the current understanding of the hematological system in the pathophysiology of acute and chronic SARS-CoV-2-associated COVID-19.