Tissue factor pathway inhibitor and the risk of recurrent venous thromboembolism

Summary

Tissue factor pathway inhibitor (TFPI) regulates factor X activation. LowTFPI is a risk factor for a first venous thrombosis. We evaluated whether low TFPI confers an increased risk of recurrent venous thromboembolism (VTE). TFPI–free antigen was measured in 611 patients with a first spontaneousVTE, and who were prospectively followed after withdrawal of anticoagulation. The endpoint was symptomatic recurrent VTE. The relative risk (RR) of recurrence increased from 1.0 (95% CI 0.4–2.6) in patients with TFPI levels ≤ 5^th percentile to 2.7 (95% CI 1.0–7.4) in patients with levels ≤ 2^nd percentile as compared with higher levels. At five years, the probability of recurrence was 48.6% (95^th CI 19.0–78.1) among patients with TFPI ≤ 2^nd percentile and 16.8% (95^th CI 13.8–19.8) among those with higher levels (p=0.04). Compared to patients with wild type factor V and high TFPI, the RR of recurrence was 1.1 (95% CI 0.7–1.7) in patients with factorV Leiden and high TFPI, 2.3 (95% CI 0.6–9.5) in patients with wild type factor V and low TFPI and 3.5 (95% CI 0.9–14.3) in patients with factor V Leiden and low TFPI. In a multivariate analysis, the high risk of recurrence in carriers of factor V Leiden and low TFPI slightly decreased [RR 2.8 (95% CI 0.6–9.5)]. We conclude that thrombosis patients with low levels of freeTFPI are at an increased risk of recurrent VTE.

Keywords

Tissue factor pathway inhibitor - venous thrombosis - recurrence - factor V Leiden

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