Signs of Hypofibrinolysis in Patients with Unprovoked Idiopathic Venous Thromboembolism

Background: The causes for venous thromboembolism (VTE) remain undetermined in at least 30% of patients with unprovoked VTE. Hypofibrinolysis may be associated to VTE, however the occurrence of hypofibrinolysis in patients with unprovoked, idiopathic, VTE is not well stablished.

Aims: To evaluate whether hypofibrinolysis would be associated with unprovoked idiopathic VTE.

Methods: Patients with a history of unprovoked VTE without acquired or inherited thrombophilia were included. Global tests of fibrinolysis, such as euglobolin lysis time (ELT) and lysis area on fibrin plate (LAFP), and specific tests of fibrinolysis, such as plasma activity plasminogen, a-2 antiplasmin (a2AP), plasminogen activator

inhibitor-1 (PAI-1), and thrombin activatable fibrinolysis inhibitor (TAFI), were performed in patients and healthy controls. We also analyzed the plasma activity of factor (F) XIII.

Results: Thirty-one patients and fifty healthy controls were included. ELT results were higher in patients than in controls (median= 295 and IQ= 205-355 minutes vs. median=250 and IQ= 167-295 minutes, respectively, p = 0.006) and LAFP values were lower in patients compared to controls (median=81 and IQ= 56-110 vs. median= 95 and IQ 72-132 respectively, p = 0.0014), suggesting that they were experiencing a hypofibrinolytic state. Plasma activity of plasminogen (median= 131 and IQ= 119-141 vs. median=120 and IQ=111-137, respectively, p = 0.045) and FXIII (median= 103 and IQ 89-127 vs. median= 96 and IQ=80-105, respectively, p = 0.050), were higher in patients than in controls, whereas plasma activity of α-2AP was lower in patients (median= 124 and IQ 114-128 vs. median= 127 and IQ=121-133, p≤0.001). Interestingly, patient's median TAFI activity was lower than in controls (median=16 and IQ 13-18μg/mL vs. median= 19 and IQ= 17-21g/mL, p≤0.001). However, PAI-1 activity did not differ between groups.

Conclusions: Hypofibrinolysis may occur in patients with unprovoked idiopathic VTE and may be detected by global tests of fibrinolysis. It is possible that hypofibrinolysis contribute to the pathogenesis of thrombosis in these selected cases.