Background and objective: Deficiencies of natural inhibitors and the presence of lupus anticoagulant are important risk factors leading to venous thromboembolic events. Before resistance to activated protein C (APC-R) was identified, the overall prevalence of inherited abnormalities of hemostasis in non-selected outpatients with venous thromboembolic disease was under 10%. This cast doubts on the of cost effectiveness and clinical significance of assaying hemostasis inhibitors in all such patients. The goal of this study is to evaluate the prevalence of inherited and acquired abnormalities of hemostasis in younger symptomatic outpatients with objectively diagnosed venous thromboembolic disease (VTD).
Methods: From October 1994 to October 1996, we diagnosed, treated and followed 191 consecutive outpatients with an objective diagnosis of venous thromboembolic disease, and assayed natural and acquired hemostasis inhibitors in 81 of them aged less than 50; in addition, 129 relatives of patients with inherited deficiencies were evaluated.
Results: Twenty-six of the patients under age 50 showed inherited deficiencies of natural inhibitors (3 antithrombin, 5 protein C, 3 protein 5 and 14 APC-R, 1 dysfibrinogenemia) and 8 patients had lupus anticoagulant (LA): abnormalities of hemostasis were found in 41.9% (95% confidence interval 31.1-53.5). In older selected patients, 60% (95% confidence interval 40.6-77.3) of the subjects showed abnormalities. Seventy-two of the relatives displayed natural inhibitor deficiencies; 88.5% of the families studied had at least one relative with the same defect as the propositus.
Interpretation and conclusions: A simple selection based on age, clinical and family history shows the existence of a high prevalence and the important clinical significance of abnormalities of hemostasis in symptomatic outpatients with venous thromboembolic disease.