Thrombophilic risk of individuals with rare compound factor V Leiden and prothrombin G20210A polymorphisms: an international case series of 100 individuals

Abstract

The risk of thrombosis in individuals with rare compound thrombophilias, homozygous factor V Leiden (FVL) plus heterozygous prothrombin G20210A (PTM), homozygous PTM plus heterozygous FVL, and homozygous FVL plus homozygous PTM, is unknown. We identified, worldwide, individuals with these compound thrombophilias, predominantly through mailing members of the International Society on Thrombosis and Haemostasis. Physicians were sent a clinical questionnaire. Confirmatory copies of the genetic results were obtained. One hundred individuals were enrolled; 58% were female. Seventy-one individuals had a venous thrombosis (includes superficial and deep vein thrombosis, and pulmonary embolism), 4 had an arterial thrombosis and 6 had both. Nineteen individuals had never had a thrombotic event. Thrombosis-free survival curves demonstrated that 50% of individuals had experienced a thrombotic event by 35 yrs of age, while 50% had a first venous thromboembolic event (VTE; includes all venous thrombosis except superficial thrombosis) by 41 yrs of age; 38.2% of first VTEs were unprovoked. 37% of patients had at least one VTE recurrence. Seventy percent of first pregnancies carried to term and not treated with anticoagulation were thrombosis-free. In conclusion, patients with these rare compound thrombophilias are not exceedingly thrombogenic, even though they have a substantial risk for VTE.

Do Factor V Leiden and Prothrombin G20210A Mutations Predict Recurrent Venous Thromboembolism in Older Patients?

“…Similarly, testing for genetic thrombophilia did not influence medical management in 77% of tested patients [10]. Evidence suggests that even combined heterozygous or single homozygous factor V Leiden or prothrombin G20210A mutations do not appear to carry a relevant venous thromboembolism recurrence risk [11] and that the venous thromboembolism risk becomes substantial only among the very rare individuals with compound homozygous mutations of these polymorphisms [12].…”

Anticoagulation Therapy in a Patient With Heterozygous Factor V Leiden and Coexisting Homozygous Prothrombin Gene Mutations

“…Prothrombin G20210A and FVL mutations are considered common thrombophilias independently. However, the presence of concomitant heterozygous FVL and homozygous prothrombin G20210A mutations is exceedingly rare, only occurring in roughly one out of 200,000 persons worldwide [6]. Patients with this rare condition are at a 17-fold higher risk of developing venous thromboembolism (VTE) than patients without this genotype [7].…”

“…The rarity of a homozygous prothrombin combined with a heterozygous FVL mutation poses new challenges in treatment options; however, research suggests that long-term use of apixaban can prevent the recurrence of VTE [6,8]. A case series showed that out of 100 patients with compound FVL mutation and prothrombin G20210A mutation, 68 experienced a VTE, and 25 of those patients experienced at least one recurrent VTE [6]. However, 72% of the patients with recurrent VTE were not receiving anticoagulants at the time of recurrence [6].…”

“…A case series showed that out of 100 patients with compound FVL mutation and prothrombin G20210A mutation, 68 experienced a VTE, and 25 of those patients experienced at least one recurrent VTE [6]. However, 72% of the patients with recurrent VTE were not receiving anticoagulants at the time of recurrence [6]. These data suggest that patients with thrombophilias should be on long-term anticoagulant therapy, such as apixaban.…”

Recurrent Cardiac Events Driven by Prothrombotic Burden in a Patient Undergoing Lipoprotein Apheresis for High Lp(a) Levels

“…This case highlights the role of thrombophilia in in luencing the therapeutic response and the risk of recurrent cardiovascular events. Current literature lacks provide evidence of causality between the presence of thrombophilia and cardiovascular events [11] and guidelines discourage the assessment of genetic testing for thrombophilia [12,13]; however, patients with a hereditary protein S, protein C or antithrombin de iciency had a high absolute risk for venous thromboembolism [14]. Moreover, hereditary thrombophilia was frequently reported in young patients [15] with acute coronary syndromes.…”