The incidence of venous thromboembolism in asymptomatic carriers of a deficiency of antithrombin, protein C, or protein S: a prospective cohort study.

Deficiencies of antithrombin, protein C, and protein S are associated with an increased risk of venous thromboembolism. The objective of this study was to prospectively assess the incidence of venous thromboembolism in nontreated asymptomatic subjects with such a deficiency. We conducted a prospective cohort study in asymptomatic family members of unselected patients who presented with a venous thromboembolic event and who were found to have a deficiency of antithrombin, protein C, or protein S. No anticoagulant prophylaxis was given to the study participants, except during risk periods for venous thromboembolism. All venous thromboembolic events were diagnosed by objective diagnostic tests. A total of 208 individuals with a mean age of 37 years (range, 15 to 79) were included in the study. A total of 611 patient observation years was obtained. Nine venous thromboembolic events occurred, resulting in an annual incidence of 1.5% (95% confidence interval [CI], 0.7 to 2.8) for the 3 deficiencies combined. Five of these events occurred spontaneously, resulting in an annual incidence of spontaneous venous thromboembolism of 0.8% (95% CI, 0.3 to 1.9). For antithrombin, protein C, and protein S deficiencies separately, this figure was 1.6%, 1.0%, and 0.4%, respectively. Thirty-four subjects experienced a total of 40 risk periods during which 4 venous thromboembolic events occurred (10% per risk period). We conclude that the use of continuous anticoagulant prophylaxis seems not warranted in asymptomatic individuals with a deficiency of antithrombin, protein C, or protein S. During risk periods for venous thromboembolism, adequate anticoagulant prophylaxis is necessary.