Abstract
Background. Factor V Leiden and prothrombin G20210A are gain-of-function mutations leading to an increased risk of venous thrombosis. They are the most common causes of thrombophilia, being present in their heterozygous form in 15–20% for factor V Leiden and 6–15% for prothrombin G20210A of unselected patients with venous thrombosis. The prevalence of each mutation in the Italian general population is 3%. Homozygous carriers for each mutation are rare, and double homozygous carriers, expected in 1 in 1.200.000 individuals, has never been described in the literature so far.
Patient. On March 3, 2005 a 30-year-old woman was admitted to the Unit of Internal Medicine, Valduce Hospital, Como, for swell and pain in the left leg. She was pregnant at the 25th gestational week. Ultrasound examination diagnosed a deep vein thrombosis of the left external and common iliac veins. She had no symptoms of pulmonary embolism. She was given nadroparin 6000 UI b.i.d. (her weight was 63 kg), elastic stockings, and was discharged on March 9, 2005. Because of worsening of the swell in the left leg, she was re-admitted on March 12, 2005 and the ultrasound examination showed an extension of the deep vein thrombosis to the left femoral-popliteal venous system. The dose of nadroparin was increased to 7000 UI b.i.d. Thrombophilia screening revealed a double homozygosity for factor V Leiden and prothrombin G20210A. Her past personal history was negative for thrombosis, but she was never exposed to high risk situations (surgery, bone fractures, prolonged immobilization, oral contraceptive use, long-haul flights) apart from a previous pregnancy which ended in miscarriage at the 6th gestational week. On June 14, 2004 she had an uneventful vaginal delivery after two hours of labour, with the last nadroparin injection in the evening before, The newborn was a female who weighted 3500 g. Her family history was also negative for thrombosis in first- and second-degree relatives despite both parents were double heterozygotes for factor V Leiden and prothrombin G20210A and brother and sister were homozygotes for factor V Leiden and heterozygotes for prothrombin G20210A.
Conclusions. The relative risk of venous thrombosis in double homozygous for factor V Leiden and prothrombin G20210A is unknown but is predicted to be extremely high. However, the patient described here had her first episode during a trigger situation, i.e., pregnancy, and severe thrombophilia seems to run an uneventful cause in her family in spite of repeated exposures to high risk situations. Hence, we shall advise the patient to stop oral anticoagulant therapy, started soon after delivery, one year after the thrombotic event.
Frequency of Thrombophilic Gene Mutations in Patients with Deep Vein Thrombosis and in Women with Recurrent Pregnancy Loss
