Low plasma levels of tissue factor pathway inhibitor in patients with congenital factor V deficiency

Abstract

Severe factor V (FV) deficiency Is associated with mild to severe bleeding diathesis, but many patients with FV levels lower than 1% bleed less than anticipated. We used calibrated automated thrombography to screen patients with severe FV deficiency for protective procoagulant defects. Thrombin generation In FV-deflclent plasma was only measurable at high tissue factor concentrations. Upon reconstitution of FV-deflclent plasma with purified FV, thrombin generation Increased steeply with FV concentration, reaching a plateau at approximately 10% FV. FV-deflclent plasma reconstituted with 100% FV generated severalfold more thrombin than normal plasma, especially at low tissue factor concentrations (1.36 pM) or in the presence of activated protein C, suggesting reduced tissue factor pathway inhibitor (TFPI) levels In FV-deficient plasma. Plasma TFPI antigen and activity levels were indeed lower (P