Low blood anticoagulant levels increase risk for VTE

By MedWire Reporters

Low plasma levels of antithrombin, protein C, and protein S significantly increase the risk for venous thromboembolism (VTE), Italian research shows.

Deficiencies in these anticoagulant proteins were each associated with a significant twofold increased risk for deep vein thrombosis (DVT) or pulmonary embolism (PE).

The risk for VTE associated with plasma levels of the naturally occurring anticoagulant proteins was not limited to predefined cutoff values, report investigators.

Instead, the risk "should be considered a continuum, being progressively higher with decreasing plasma levels of these proteins and also present for low borderline levels," according to Paolo Bucciarelli (Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan) and colleagues.

The incidence of VTE in the general population is approximately 1-2 cases per 1000 person-years. It develops without any cause in about 40% of cases.

Antithrombin, protein C, and protein S are anticoagulant proteins that play a role in control of thrombus formation. Inherited deficiencies in these proteins, although rare, are a strong risk factor for VTE.

In the present study, the researchers hypothesized that varying levels of antithrombin, protein C, and protein S might explain some of variable thrombotic risk in individuals at genetic risk for VTE. Such individuals carry mutations in the factor V Leiden and prothrombin genes (FII G20210A).

Published in the Journal of Thrombosis and Haemostatsis, the case-control study included 1401 patients with documented VTE and 1847 healthy controls.

For all three anticoagulant proteins, a dose-response effect was observed, with the risk for VTE higher among individuals with reduced plasma concentrations of the proteins.

For every 20 IU/dL decrease in plasma levels of antithrombin, the risk for VTE increased by 43%, and for every 20 IU/dL decrease in plasma levels of both protein C and protein S, the risk for VTE increased by 13%.

The increased risk for VTE was statistically significant with antithrombin levels between 76 and 85 IU/dL and for protein C and protein S levels between 61 and 75 IU/dL. For antithrombin, even plasma levels considered normal increased the risk for VTE.

In addition, the risk for VTE in factor V Leiden or prothrombin G20210A was two- to threefold higher even in patients with low-to-borderline antithrombin or protein C and protein S levels.

Based on these findings, specifically the demonstrated dose-response effect on the risk for VTE, the researchers conclude these anticoagulant proteins "should be considered in the assessment of individual VTE risk."

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