Targeting tissue factor pathway inhibitor with concizumab to improve hemostasis in patients with Glanzmann thrombasthenia: an in vitro study.
Research article published in Journal of thrombosis and haemostasis : JTH (2024)
Abstract
BACKGROUND: Glanzmann thrombasthenia (GT) is caused by an inherited defect of platelet αIIbβ3 integrin. Concizumab, a monoclonal antibody specific for tissue factor pathway inhibitor, abolishes its anticoagulant effect. OBJECTIVES: To evaluate the in vitro ability of concizumab to improve hemostasis in GT. METHODS: The effects of concizumab were evaluated in whole blood or platelet-rich plasma from GT patients (n = 5-9) using a thrombin generation assay, rotational thromboelastometry (ROTEM), a global fibrinolytic capacity assay, and a flow chamber assay (Total Thrombus formation Analysis System). Washed platelets (WPs) and 20 nM recombinant activated factor VII (rFVIIa) were included for comparison. RESULTS: The lag time in the thrombin generation assay was significantly longer (+85%; P < .0001) in GT patients than in controls. WPs, rFVIIa, and concizumab each significantly improved thrombin generation profiles. The ROTEM clotting time (CT) was significantly longer in GT patients than in controls (677 seconds vs 523 seconds; P = .03). However, CT improved after adding WPs, rFVIIa, or concizumab. Under flow, occlusive thrombi were present in all healthy controls after 10 minutes, whereas platelet-fibrin depositions were not seen in GT patients. Subocclusive or occlusive thrombi formed when GT blood was mixed with WPs, rFVIIa, or concizumab. Clots in GT platelet-rich plasma were more susceptible to fibrinolysis and were improved by WPs, rFVIIa, or concizumab. CONCLUSION: Concizumab enhanced thrombin generation, decreased the ROTEM CT, improved thrombus formation under flow, and reduced clot lysis. Our results demonstrate the potential of concizumab for subcutaneous prophylaxis in GT patients.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Zusammenfassung
Glanzmann thrombasthenia (GT) is caused by an inherited defect of platelet αβintegrin. Concizumab, a monoclonal antibody specific for tissue factor pathway inhibitor, abolishes its anticoagulant effect.
Warum dies für die Hirudotherapie relevant ist
Diese In-vitro-Studie untersuchte, ob Concizumab, ein monoklonaler Antikörper gegen den Tissue-Factor-Pathway-Inhibitor, die Hämostase in Blutproben von Patienten mit Glanzmann-Thrombasthenie verbessern kann. Concizumab verstärkte die Thrombingenerierung, verkürzte die Gerinnungszeit in der Thromboelastometrie und verbesserte die Thrombusbildung unter Flussbedingungen in den Proben von GT-Patienten. Diese Arbeit ist nur insofern für das Gebiet der ASH relevant, als sie sich mit der antikoagulatorischen/prokoagulatorischen Modulation Thrombin-bezogener Signalwege befasst – derselben enzymatischen Achse, die Hirudin adressiert. Die Studie beinhaltet jedoch keine Blutegel, kein Hirudin und keine aus Blutegeln gewonnenen Agenzien, wodurch ihre Relevanz für die Hirudotherapie indirekt und begrenzt ist.
Zitation
Targeting tissue factor pathway inhibitor with concizumab to improve hemostasis in patients with Glanzmann thrombasthenia: an in vitro study.
Dubut et al. · Journal of thrombosis and haemostasis : JTH, 2024
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