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.
Resumen
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.
Por qué esto importa para la hirudoterapia
Este estudio in vitro evaluó si el concizumab, un anticuerpo monoclonal dirigido contra el inhibidor de la vía del factor tisular, podría mejorar la hemostasia en muestras de sangre de pacientes con trombastenia de Glanzmann. El concizumab aumentó la generación de trombina, mejoró el tiempo de coagulación en la tromboelastometría y mejoró la formación de trombos bajo flujo en muestras de pacientes con TG. Este trabajo solo es relevante para el ámbito de la ASH en el sentido amplio de que concierne a la modulación anticoagulante/procoagulante de las vías relacionadas con la trombina, el mismo eje enzimático que la hirudina ataca. Sin embargo, el estudio no involucra sanguijuelas, hirudina ni agentes derivados de sanguijuela, por lo que su relevancia para la hirudoterapia es indirecta y limitada.
Citación
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
Contexto clínico relacionado
Explore cómo esta investigación se conecta con la práctica clínica
Añadido a la biblioteca ASH: May 28, 2026 · Última actualización del sitio: June 18, 2026