Author(s): Martinelli I, Mannucci PM, De Stefano V, Taioli E, Rossi V,
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Abstract Deficiency of the naturally occurring anticoagulant proteins, such as antithrombin, protein C and protein S, and activated protein C resistance due to the factor V Leiden gene mutation is associated with inherited thrombophilia. So far, no direct comparison of the thrombotic risk associated with these genetic defects is available. In this study, we wish to compare the lifetime probability of developing thrombosis, the type of thrombotic symptoms, and the role of circumstantial triggering factors in 723 first- and second-degree relatives of 150 index patients with different thrombophilic defects. We found higher risks for thrombosis for subjects with antithrombin (risk ratio 8.1, 95\% confidence interval [CI], 3.4 to 19.6), protein C (7.3, 95\% CI, 2.9 to 18.4) or protein S deficiency (8.5, 95\% CI, 3. 5 to 20.8), and factor V Leiden (2.2, 95\% CI, 1.1 to 4.7) than for individuals with normal coagulation. The risk of thrombosis for subjects with factor V Leiden was lower than that for those with all three other coagulation defects (0.3, 95\% CI, 0.1 to 1.6), even when arterial and superficial vein thromboses were excluded and the analysis was restricted to deep vein thrombosis (0.3, 95\% CI, 0.2 to 0.5). No association between coagulation defects and arterial thrombosis was found. The most frequent venous thrombotic manifestation was deep vein thrombosis with or without pulmonary embolism (90\% in antithrombin, 88\% in protein C, 100\% in protein S deficiency, and 57\% in factor V Leiden), but a relatively mild manifestation such as superficial vein thrombosis was common in factor V Leiden (43\%). There was a predisposing factor at the time of venous thromboembolism in approximately 50\% of cases for each of the four defects. In conclusion, factor V Leiden is associated with a relatively small risk of thrombosis, lower than that for antithrombin, protein C, or protein S deficiency. In addition, individuals with factor V Leiden develop less severe thrombotic manifestations, such as superficial vein thrombosis.
This article was published in Blood
and referenced in JBR Journal of Clinical Diagnosis and Research