Blood 1998, 92(7): 2353-2358
Martinelli,Ida; Manucci,M; De Stefano,Valerio; Taioli,Emanuela; Rossi,Valentina; Crosti,Francesca; Paciaroni,Katia; Leone,Giuseppe; Faioni,Elena
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.