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Pro- and anticoagulant factors facilitate thrombin generation and balance the haemostatic response to FEIBA(®) in prophylactic therapy.
- Source :
-
Haemophilia : the official journal of the World Federation of Hemophilia [Haemophilia] 2016 Jul; Vol. 22 (4), pp. 615-24. Date of Electronic Publication: 2016 Feb 15. - Publication Year :
- 2016
-
Abstract
- Introduction: 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).<br />Methods: 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.<br />Results: 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.<br />Conclusion: These experiments showed that although the FII-FXa complex induced immediate thrombin formation on the activated platelet surface, other procoagulant components of FEIBA were necessary to achieve an optimal thrombin burst. The presence of the pro- and anti-coagulants in FEIBA provides a haemostatic balance, and is thus expected to prevent thrombotic events. Recent clinical data verified the postulated MoA of FEIBA in prophylaxis treatment.<br /> (© 2016 The Authors. Haemophilia Published by John Wiley & Sons Ltd.)
Details
- Language :
- English
- ISSN :
- 1365-2516
- Volume :
- 22
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Haemophilia : the official journal of the World Federation of Hemophilia
- Publication Type :
- Academic Journal
- Accession number :
- 26879158
- Full Text :
- https://doi.org/10.1111/hae.12873