Inherited Thrombophilia

Factor V Leiden Mutation

Factor V Leiden is found in approximately 5% of Caucasians. Patients with this mutation will be at higher risk of experiencing a venous clot than others in the community. In fact the Factor V Leiden mutation is found in approximately 15% of all patients with first time clots. Furthermore, the mutation is found in 40% of young people, and 60% of pregnant women with venous clots. The Factor V Leiden mutation is also associated with increased complications during pregnancy, such as pre-eclampsia, recurrent miscarriage, stillbirth and pulmonary embolism.

Women who have one copy of the Factor V leiden mutation and are taking oral contraceptives have an even higher risk of venous clot formation.

Prothrombin 20,210 Mutation

Another gene associated with increasing your risk for abnormal venous clotting is called Prothrombin or Factor II. The DNA change that leads to the increased risk is known as Prothrombin 20,210. This DNA change is found in about 1-2% of Caucasians and in up to 8% of patients experiencing their first venous clot.

Lifetime Risk Increase for developing a venous clot

Family members of people who are known to carry these mutations are also advised to seek testing. Preventative treatment can be instigated during periods of increased risk, such as surgery, pregnancy or immobility). Also people at risk can avoid risk factors such as smoking, oestrogen therapy and oral contraception.

References

1. Poort SR, Rosendaal FR, Reitsma PH, Bertina RM. A common genetic variation in the 3’-untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increase in venous thrombosis. Blood. 1996;88:3698-3703.
2. Gerhardt A, Scharf RE, Beckmann MW, et al. Prothrombin and factor V mutations in women with a history of thrombosis during pregnancy and the puerperium. N Engl J Med. 2000;342:374-380.
3. Foka ZJ, Lambropoulos AF, Saravelos H, et al. Factor V Leiden and prothrombin G20210A mutations, but not methylenetetrahydrofolate reductase C677T, are associated with recurrent miscarriages. Hum Reprod. 2000;15:458-462.
4. Schobess R, Junker R, Auberger K, et al. Factor V G1691A and prothrombin G20210A in childhood spontaneous venous thrombosis – Evidence of an age-dependent thrombotic onset in carriers of factor V G1691A and prothrombin G20210A mutation. Eur J Pediatr. 1999;158(Suppl 3):S105-S108.
5. Martinelli I, Sacchi E, Landi G, et al. High risk of cerebral-vein thrombosis in carriers of a prothrombin-gene mutation and in users of oral contraceptives. N Engl J Med. 1998;338:1793-1797.
6. Reich L, Bower M, Key NS. Role of geneticist in testing and counseling for inherited thrombophilia. Genet Med 2003; 5(3):133-143.