Abstract
Venous thromboembolism (VTE) is a chronic disease, which tends to recur. Whether an abnormal fibrinolytic system is associated with an increased risk of VTE is unclear. We assessed the relationship between fibrinolytic capacity (reflected by clot lysis time [CLT]) and risk of recurrent VTE. We followed 704 patients (378 women; mean age 48 yrs) with a first unprovoked VTE for an average of 46 months after anticoagulation withdrawal. Patients with natural coagulation inhibitor deficiency, lupus anticoagulant, cancer, homozygosity for factor V Leiden or prothrombin mutation, or requirement for indefinite anticoagulation were excluded. Study endpoint was symptomatic recurrent VTE. For measurement of CLT, a tissue factor-induced clot was lysed by adding tissue-type plasminogen activator. Time between clot formation and lysis was determined by measuring the turbidity.135 (19%) patients had recurrent VTE. For each increase in CLT of 10 minutes, the crude relative risk (RR) of recurrence was 1.13 (95% CI 1.02–1.25; p = 0.02) and was 1.08 (95% CI 0.98–1.20; p = 0.13) after adjustment for age and sex. For women only, the adjusted RR was 1.14 (95% CI, 0.91–1.42, p = 0.22) for each increase in CLT of 10 minutes. CLT values in the 4th quartile of the female patient population, as compared to values in the 1st quartile, conferred a risk of recurrence of 3.28 (95% CI, 1.07–10.05; p = 0.04). No association between CLT and recurrence risk was found in men. Hypofibrinolysis as assessed by CLT confers a moderate increase in the risk of recurrent VTE. A weak association between CLT and risk of recurrence was found in women only.
Highlights
A third of patients with first unprovoked venous thromboembolism (VTE) have recurrence of VTE within 5 years after completion of anticoagulant therapy [1]
A total of 121 patients left the study because they required antithrombotic treatment for causes other than venous thrombosis (65 patients), or because they were given a diagnosis of cancer (16), because they became pregnant (29) or for other reasons (11). 36 patients were lost to follow-up
clot lysis time (CLT) values in the 4th quartile, as compared to values in the 1st quartile, conferred a 2.7fold risk of recurrence after adjustment for age. In this prospective cohort study of more than 700 patients with a first unprovoked VTE the risk of recurrent VTE was as high as 21% 5 years after withdrawal of anticoagulants
Summary
A third of patients with first unprovoked venous thromboembolism (VTE) have recurrence of VTE within 5 years after completion of anticoagulant therapy [1]. Current guidelines recommend extended anticoagulation in patients with unprovoked proximal deep vein thrombosis (DVT) or pulmonary embolism (PE) provided they have a low bleeding risk and coagulation monitoring can be accomplished at regular intervals [2]. This recommendation, implies that many patients who do not experience recurrence are unnecessarily exposed to a bleeding risk. A better stratification of patients with regard to their recurrence risk can be achieved by measuring coagulation activation markers such as D-Dimer or in vitro thrombin generation [1]
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