Targeting Tissue Factor Pathway Inhibitor with concizumab to improve haemostasis in patients with Glanzmann thrombasthenia: an in vitro study. - Archive ouverte HAL
Article Dans Une Revue Journal of Thrombosis and Haemostasis Année : 2024

Targeting Tissue Factor Pathway Inhibitor with concizumab to improve haemostasis in patients with Glanzmann thrombasthenia: an in vitro study.

Résumé

Glanzmann thrombasthenia (GT) is caused by an inherited defect of platelet αβ integrin. Concizumab,a monoclonal antibody specific for Tissue Factor Pathway Inhibitor (TFPI), abolishes its anticoagulant effect. To evaluate the in vitro ability of concizumab to improve haemostasis in GT. The effects of concizumab were evaluated in whole blood or platelet-rich plasma (PRP) from GT patients (n=5-9) using a thrombin generation assay (TGA), rotational thromboelastometry (ROTEM), a global fibrinolytic capacity assay and a flow-chamber assay (T-TAS). Washed platelets (WP) and 20 nM recombinant activated factor VIIa (rFVIIa) were included for comparison. The lag time in the TGA was significantly longer (+85%, p<0.0001) in GT patients than in controls. WP, rFVIIa and concizumab each significantly improved thrombin generation profiles. The ROTEM clotting time was significantly longer in GT patients than in controls (677 s vs 523 s; p=0.03). However, CT improved after adding WP, rFVIIa or concizumab. Under flow, occlusive thrombi were present in all healthy controls after 10 min, whereas platelet-fibrin depositions were not seen in GT patients. Sub-occlusive or occlusive thrombi formed when GT blood was mixed with WP, rFVIIa or concizumab. Clots in GT PRP were more susceptible to fibrinolysis and were improved by WP, rFVIIa or concizumab. 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.

Dates et versions

hal-04637041 , version 1 (05-07-2024)

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Jade Dubut, Valérie Goin, Cloé Derray, Yoann Huguenin, Mathieu Fiore. Targeting Tissue Factor Pathway Inhibitor with concizumab to improve haemostasis in patients with Glanzmann thrombasthenia: an in vitro study.. Journal of Thrombosis and Haemostasis, 2024, ⟨10.1016/j.jtha.2024.05.033⟩. ⟨hal-04637041⟩

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