Factor V leiden and Prothrombin Gene Mutations: Differences by Gender

Factor V Leiden (FVL) and prothrombin gene mutation (PT) are the most common cause of inherited thrombophilia in Caucasian populations, accounting for 40 to 50 % of cases. The incidence of inherited thrombophilia in subjects with a deep vein thrombosis ranges from 24 to 37 %. Women with factor V Leiden or prothrombin gene mutation have a substantially increased risk of clotting in pregnancy and on estrogen -containing birth control pills or hormone replacement in the form of deep vein thrombosis (DVT) and pulmonary embolism (PE). There have been multiple studies done in regards to thrombophilia in women but few reports specific to the behavior of these mutations in men.

To investigate the difference in clinical presentations of men vs women with Factor V Leiden and prothrombin gene mutations. Methods: A retrospective study of patients (pts) over the age of 18 years (yrs) with FVL and PT mutation with history of thrombosis was conducted. These pts were followed in Comprehensive Hemophilia and Thrombosis Disorder Center at Newark Beth Israel Medical Center (NBIMC).

72 pts with symptomatic diagnoses of FVL or PT mutation were identified. The female to male ratio was (43/17) 2:1. Of the male patients 13/17 (76%) had FVL mutation and 4/17(24%) had PT gene mutation. The mean age was 32 yrs (range18–54 yrs). The majority, 15/17(88%) had a lower extremity DVT; 2/17(12%) had PE at presentation. 13/15(86%) of the DVTs were provoked: 5/13 (38%) had surgery, 5/13(38%) had history of recent travel, 3/13(24%) had history of trauma. Of the male pts 11/17 (65%) of the pts had a family history of thrombophilia. 9/17 (53%) had a second thrombotic event with a mean time of 10 yrs (range 1–30 years). Of the female pts 31/43(72%) were diagnosed with FVL gene mutation and 12/43(28%) with PT mutation. The mean age was 32 yrs (18–79 yrs). Of the females 13/43(30%) presented with pregnancy loss, 11/43(23%) with a provoked lower extremity DVT [ 3/43 (6%) had history of oral contraceptive pills use, 5/43(12%) with recent surgery, 2/43(5%) with pregnancy, 1/43(2%) with travel history], 5/43 (12%) had unprovoked DVT, and 13/43(30%) had other thrombotic events (2/43 (5%)CVA, 1/43 (2%)neck vein thrombosis, 1/43(2%) arteriovenous fistula thrombosis, 6/43 (14%) PE, 1/43(2%)with retinal artery thrombosis, 1/43 (2%) with mesenteric ischemia, and 1/43(2%) with portal vein thrombosis). In this group 21/43(49%) had a family history of thrombophilia. Second events occurred in 8/43(18%) with a mean time to recurrence of 7 yrs (range 1–41 yrs).

Clinical presentations in patients with FVL and PT mutations differ between males and females including location, time to recurrence and associated conditions. First events in females included both arterial and venous thrombosis and were predominantly hormone related. In contrast, the most common site of thrombosis in our male pts was a provoked lower extremity venous thrombosis especially post surgery and prolonged travel. Additionally, males had higher recurrent events. Prospective long term outcome studies of patients and their asymptomatic family members are necessary to confirm these differences.

No relevant conflicts of interest to declare.