Long-term oral anticoagulation with acenocoumarol significantly reduced ex vivo thrombin generation compared to healthy controls, but these parameters did not correlate with INR values.
Observational (n=90)
Does chronic oral anticoagulation with acenocoumarol alter ex vivo thrombin generation compared to healthy controls, and do these parameters correlate with INR in patients with VTE or AF?
In patients with VTE or AF on chronic oral anticoagulation, INR values do not correlate with ex vivo thrombin generation, suggesting that other mechanisms like the protein C system play an important role in controlling hemostasis.
International normalized ratio (INR) is used to monitor chronic oral anticoagulant (OA) treatment; however, it is poorly understood how this simple test reflects in vivo hemostatic reactions, culminating in thrombin generation and clot formation. We studied the process of thrombin generation using an ex vivo model, where thrombin-antithrombin (TAT) complexes are measured in blood emerging from standardized skin incisions in 55 patients (35 with venous thromboembolism VTE and 20 with sustained atrial fibrillation AF) treated with acenocoumarol (INR 2.0-3.0). In addition, in venous blood, we measured the activity of factor VIII (FVIII) and vitamin K-dependent coagulation proteins. Chronic anticoagulation led to significant reductions in maximum TAT concentrations as compared to 35 healthy controls, in maximum TAT generation rates, and in mean amount of thrombin generated. Parameters of thrombin generation did not correlate with INR or any coagulation factor measured. International normalized ratio was significantly and independently affected by the decrease in the activity of all vitamin K-dependent coagulation proteins. The strongest influence was shown for FVII. Factor VIII activity was increased in all patients studied independently of the duration of anticoagulation and did not change over time. In conclusion, in patients with VTE and AF on OA, there is no correlation between INR values and parameters of ex vivo thrombin generation. This may indicate an important role of protein C (PC) system and possibly other endothelium-dependent mechanisms in controlling hemostasis. Increased FVIII activity in patients with VTE and AF does not change significantly during anticoagulation and is probably related to the pretreatment prothrombotic state.
Musiał et al. (Tue,) conducted a observational in Venous thromboembolism or atrial fibrillation (n=90). Acenocoumarol (oral anticoagulation) vs. Healthy controls was evaluated on Ex vivo thrombin generation (maximum TAT concentrations, generation rates, and mean amount) and correlation with INR. Long-term oral anticoagulation with acenocoumarol significantly reduced ex vivo thrombin generation compared to healthy controls, but these parameters did not correlate with INR values.