Pro- and anticoagulant factors facilitate thrombin generation and balance the haemostatic response to FEIBA(®) in prophylactic therapy

Haemophilia : the Official Journal of the World Federation of Hemophilia
K VáradiP L Turecek

Abstract

FEIBA(®) consists of zymogens and traces of activated forms of procoagulant factors II, VII, IX, X, anticoagulants protein C and TFPI, and small amounts of cofactors FV, FVIII and protein S, in a balanced ratio. As shown previously, FII-FXa complex plays a key role in FEIBA's mode of action (MoA). Thrombin generation (TG) was measured by spiking coagulation factors, cofactors and inhibitors to high titer FVIII inhibitor plasma, and in plasma samples from patients in a phase 3 clinical study evaluating the safety and efficacy of FEIBA prophylaxis in haemophilia A patients with inhibitors. Increasing the FXa/FII ratio improved TG, while adding coagulation enzyme components had a negligible effect. Adding FX, FIX, and FVII increased the peak thrombin and decreased the lag time. The presence of FV and phospholipids led to faster TG, while protein C and protein S reduced the amount of peak thrombin. TFPI appeared to have no effect. Patients on prophylaxis with FEIBA(®) showed higher peak thrombin and AUC with elevated FII, FX, FIX, FVIIa, and protein C levels, and experienced significantly less bleeding episodes than those receiving on-demand treatment. These experiments showed that although the FII-FXa complex induced immediate thr...Continue Reading

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Citations

Jun 12, 2018·Journal of Thrombosis and Haemostasis : JTH·R HartmannF Scheiflinger
Feb 6, 2019·VASA. Zeitschrift für Gefässkrankheiten·Paul Gressenberger
Sep 26, 2017·The Cochrane Database of Systematic Reviews·Chatree Chai-AdisaksophaBarbara A Konkle
Oct 29, 2017·Journal of Thrombosis and Haemostasis : JTH·J D BeckmanA S Wolberg
Jan 19, 2018·Nature Reviews. Cardiology·Jerrold H LevyJeffrey I Weitz
May 11, 2020·Blood Cells, Molecules & Diseases·Puja SoniShrimati Shetty

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