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  • Title: Oral contraceptives enhance the risk of clinical manifestation of venous thrombosis at a young age in females homozygous for factor V Leiden.
    Author: Rintelen C, Mannhalter C, Ireland H, Lane DA, Knöbl P, Lechner K, Pabinger I.
    Journal: Br J Haematol; 1996 May; 93(2):487-90. PubMed ID: 8639453.
    Abstract:
    In 29 patients (17 females) homozygous Arg 506 Gln mutation (FV Leiden) was identified. 25 had been investigated because of venous thromboembolism (VTE); four asymptomatic patients were found during family studies. The first VTE had occurred significantly earlier in females (median age [m] 26 years, range 17-49) than in males (m=38 years, range 21-82) (P=0.01). 12 females (80%) had taken oral contraceptives (OC, estrogen content 0.02-0.1 mg) for 6-150 months prior to thrombosis. Further triggering conditions in females were hormone replacement (n=1) and pregnancy (n=2). In 8/10 males the first VTE had occurred spontaneously--in two after surgery. The sites of VTE were deep vein thrombosis, pulmonary embolism, caval vein thrombosis and superficial thrombophlebitis. From our data we conclude that OC medication is the most important precipitating factor for VTE in females with homozygous FV Leiden. During June 1994 to September 1995, in Austria, 25 patients homozygous for factor V Leiden who developed venous thrombosis were referred to the General Hospital in Vienna. Retrospective analysis was conducted of these patients and of 4 asymptomatic homozygous patients identified during family studies to identify other risk factors that might contribute to the development of thrombosis in homozygous patients. Factor V Leiden prevents production of an important inhibitor of blood coagulation, thereby increasing the risk of venous thrombosis 3-7 fold in heterozygous individuals and 80-fold in homozygous individuals. The subjects included 17 females and 12 males. The women experienced their first thromboembolic event at an earlier age than men (median, 26 vs. 38; p 0.01). 80% of the women experienced this first event while using combined oral contraceptives (OCs) (estrogen content, 0.02-0.1 mg). The interval between OC use and first thrombosis ranged from 6 to 150 months. One woman developed her first thrombosis 12 months after beginning hormone (4 mg estrogen) replacement therapy. 13% of the female patients had thromboembolic events during pregnancy. 80% of the men had no precipitating cause for thrombosis. Two men had an additional risk factor (i.e., surgery). These findings clearly suggest that OC use puts women with homozygous factor V Leiden at an unacceptably high risk of venous thrombosis. Health personnel should consider the medical and socioeconomic benefits of routine screening for factor V Leiden to identify both homozygous and heterozygous women considering OC use.
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