FVIII/VWF complex displays a greater pro‐haemostatic activity than FVIII preparations devoid of VWF: Study in plasma and cell‐based models. Issue 4 (23rd April 2020)

• Record Type: Journal Article
• Authors: Ammollo, Concetta T.; Semeraro, Fabrizio; Vitulli, Antonia; Dirienzo, Lavinia; Mezzasoma, Anna M.; Semeraro, Nicola; Gresele, Paolo; Colucci, Mario
• Is Part Of: Haemophilia. Volume 26:Issue 4(2020)
• Page Start: e151
• Page End: e160
• Publication Date: 2020-04-23
• Subjects: coagulation -- endothelial cells -- fibrinolysis -- inhibitor -- thrombin -- thrombin‐activatable fibrinolysis inhibitor; Hemophilia -- Periodicals; 616.1572005
• DOI: 10.1111/hae.14008
• Languages: English
• ISSNs: 1351-8216

Abstract

Abstract: Introduction: Plasma‐derived FVIII/VWF complex was reported to be less sensitive to inhibitors than FVIII preparations devoid of VWF. Aim: To compare the efficacy of FVIII/VWF complex (Fanhdi) and five different VWF‐free FVIII preparations in restoring thrombin generation and activation of thrombin‐activatable fibrinolysis inhibitor (TAFI) in haemophilic plasma, with and without inhibitor, and in cell‐based models. Methods: Experiments were performed in haemophilic plasma supplemented with inhibitory IgG or in plasma samples obtained from haemophilia A patients without (n = 11) and with inhibitor (n = 12). Thrombin generation was evaluated by calibrated automated thrombography (CAT) under standard conditions, in the presence of activated protein C (APC) or thrombomodulin (TM), and in cell‐based models including endothelial cells, either alone or in combination with platelets or tissue factor‐expressing blood mononuclear cells. The kinetics of TAFI activation was determined by a two‐stage functional assay in the absence and in the presence of APC. Results: In haemophilic plasma without inhibitor, Fanhdi enhanced thrombin generation and TAFI activation as well as recombinant (2nd‐4th generation) and plasma‐derived FVIII preparations devoid of VWF. On the contrary, in plasma with inhibitor, Fanhdi displayed a greater ability to restore thrombin generation and TAFI activation under all tested conditions. Notably, in cell‐based models including endothelial cells, Fanhdi proved more efficient than all other preparations in improving thrombin generation even in the absence of inhibitor. Conclusion: The greater pro‐haemostatic activity of FVIII/VWF complex, either in haemophilic plasma with inhibitor or in the presence of endothelial cells, may offer therapeutic advantages.