Premium
Effect of warfarin treatment on thrombin activatable fibrinolysis inhibitor ( TAFI ) activation and TAFI ‐mediated inhibition of fibrinolysis
Author(s) -
Incampo F.,
Carrieri C.,
Galasso R.,
Scaraggi F. A.,
Di Serio F.,
Woodhams B.,
Semeraro N.,
Colucci M.
Publication year - 2013
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/jth.12102
Subject(s) - fibrinolysis , thrombin , plasmin , chemistry , thromboelastography , medicine , pharmacology , coagulation , endocrinology , biochemistry , platelet , enzyme
Summary Background Severe clotting deficiencies are associated with enhanced in vitro fibrinolysis due to insufficient thrombin activatable fibrinolysis inhibitor (TAFI) activation. Because oral anticoagulant therapy ( OAT ) with warfarin causes a partial deficiency of vitamin K‐dependent factors, its effect on clot lysability remains unclear. Objectives To evaluate plasma and blood fibrinolytic capacity in patients under stable OAT ( n = 221) as compared with controls ( n = 132). Methods Fibrinolysis resistance of plasma (turbidimetry) and blood (thromboelastography) clots was calculated as the lysis time of tissue factor‐induced clots exposed to 30 and 100 ng mL −1 t‐PA, respectively. Results Plasma PAI‐1 was similar in the two groups, whereas TAFI was slightly lower in patients. OAT plasma clots lysed faster than controls ( P = 0.001). The addition of the TAFI a inhibitor PTCI reduced lysis time by 14% in OAT and 34% in controls, and the difference between the groups disappeared. Similar data were obtained with blood clots. Thrombin and TAFIa generation in OAT plasma amounted to roughly 50% of controls, supporting a reduced thrombin‐dependent TAFI activation. Clot resistance of OAT plasma was normalized by Ba‐citrate plasma eluate or prothrombin but not by BaSO 4 serum eluate, rFVII a or FX . Surprisingly, circulating levels of TAFI a and its inactive derivative TAFI ai were higher in warfarin patients ( P < 0.0001) and correlated with plasmin‐antiplasmin ( P = 0.0001) but not with prothrombin F 1 + 2 . Conclusions OAT enhances both plasma and blood fibrinolysis by reducing thrombin‐dependent TAFI activation, a phenomenon largely determined by low prothrombin levels. At variance with in vitro data, ‘basal’ in vivo TAFI a/ai levels seem related to plasmin rather than thrombin generation.