Article A panhaemocytometric approach to COVID-19: a retrospective study on the importance of monocyte and neutrophil population data on Sysmex XN-series analysers was published on April 1, 2021 in the journal Clinical Chemistry and Laboratory Medicine (CCLM) (volume 59, issue 5).

SARS-CoV-2 cell–cell fusion and syncytiation is an emerging pathomechanism in COVID-19, but the precise factors contributing to the process remain ill-defined. In this study, we show that metalloproteases promote SARS-CoV-2 spike protein-induced syncytiation in the absence of established serine proteases using in vitro cell–cell fusion assays. We also show that metalloproteases promote S2′-activation of the SARS-CoV-2 spike protein, and that metalloprotease inhibition significantly reduces the syncytiation of SARS-CoV-2 variants of concern. In the presence of serine proteases, however, metalloprotease inhibition does not reduce spike protein-induced syncytiation and a combination of metalloprotease and serine protease inhibition is necessitated. Moreover, we show that the spike protein induces metalloprotease-dependent ectodomain shedding of the ACE2 receptor and that ACE2 shedding contributes to spike protein-induced syncytiation. These observations suggest a benefit to the incorporation of pharmacological inhibitors of metalloproteases into treatment strategies for patients with COVID-19.

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.

Article A panhaemocytometric approach to COVID-19: the importance of cell population data on Sysmex XN-series analysers in severe disease was published on November 29, 2022 in the journal Clinical Chemistry and Laboratory Medicine (CCLM) (volume 0, issue 0).