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 wa s to prospectively assess the incidence of venous thromboembolism in nontre ated asymptomatic subjects with such a deficiency. We conducted a prospecti ve cohort study in asymptomatic family members of unselected patients who p resented with a venous thromboembolic event and who were found to have a de ficiency of antithrombin, protein C, or protein S. No anticoagulant prophyl axis was given to the study participants, except during risk periods for ve nous thromboembolism. All venous thromboembolic events were diagnosed by ob jective 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 [Cl], 0. 7 to 2.8) for the 3 deficiencies combined. Five of these events occurred sp ontaneously, resulting in an annual incidence of spontaneous venous thrombo embolism of 0.8% (95% CI, 0.3 to 1.9). For antithrombin, protein C,and prot ein S deficiencies separately, this figure was 1.6%, 1.0%, and 0.4%, respec tively. Thirty-four subjects experienced a total of 40 risk periods during which 4 venous thromboembolic events occurred (10% per risk period). We con clude that the use of continuous anticoagulant prophylaxis seems not warran ted in asymptomatic individuals with a deficiency of antithrombin, protein C, or protein S. During risk periods for venous thromboembolism, adequate a nticoagulant prophylaxis is necessary. (C) 1999 by The American Society of Hematology.