The 2 main causes of arterial thromboembolism are certainly arteriosclerosis and atrial fibriallation. Only uncommonly do arterial clots occur in persons less than 40 or 50 years of age who do not have arteriosclerosis or atrial fibrillation. Under these circumstances, a number of uncommon conditions, including thrombophilias, should be considered and investigated (see table 1: Causes and work-up).
Thrombophilias do not play much of a role in arterial thrombosis. Heterozygous factor V Leiden and heterozygous prothrombin 20210 mutation by themselves do not (factor V Leiden) or only minimally (prothrombin 20210 mutation) increase the risk for arterial thromboembolism (ref 1). Whether the risk is increased in the individual with homozygous factor V Leiden, homozygous prothrombin 20210 mutation, and double heterozygous individual (who has both factor V Leiden and the prothrombin 20210 mutation) is not known. Protein C deficiency and protein S deficiency appear to put a person at moderately increased risk for arterial clots (ref 2). Whether antithrombin deficiency is a risk factor is not clear; recent data suggest, that it may not (ref 2). MTHFR polymorphisms are not a risk factor for arterial thrombosis in the U.S., where food is supplemented with folic acid (ref 3).
What do I test in patients with unexplained arterial clots?
I consider the possible underlying causes listed in table 1, and consider doing the thrombophilia work-up listed as well. The reason I consider a thrombophilia work-up is to detect a “strong thrombophilia”. However, I acknowledge the fact that it is not known whether individuals with arterial clots who are found to have one of the strong thrombophilias are more effectively treated with anti-platelet therapy or anticoagulants. Indivdiualized decisions need to be made.
Special anatomic causes
Some special considerations in patients with unexplained arterial clots are: (a) in the case of upper extremity arterial thromboembolism: thoracic outlet syndrome should be considered; (b) in lower extremity arterial thromboembolism: popliteal artery entrapment syndrome, cystic adventitial disease of the popliteal artery, fibromuscular dysplasia of the lower-extremity arteries, and endofibrosis of the iliac; and (c) in the case of stroke in the young, spontaneous or traumatic cervical artery dissection.
Patients with arterial thromboembolism due to arteriosclerosis are typically treated with anti-platelet drugs. Patients with atrial fibrillation and arterial thromboembolism are typically treated with anticoagulation, i.e. warfarin (Coumadin®, Jantoven®) or one of the new oral anticoagulants. As mentioned above, it is not known whether individuals with arterial clots and a strong thrombophilia are more effectively treated with anti-platelet therapy or anticoagulants.
- Kim RJ et al. Association between factor V Leiden, prothrombin G20210A, and methylenetetrahydrofolate reductase C677T mutations and events of the arterial circulatory system: a meta-analysis of published studies. Am Heart J 2003; 146:948-957.
- Mahmoodi BK, Brouwer JLP, Veeger NJGM, Van der Meer J. Hereditary deficiency of protein C or protein S confer increased risk of arterial thromboembolic events at a young age. Results from a large family cohort study. Circulation 2008; 118:1659-1667.
- Klerk M. MTHFR 677C–>T polymorphism and risk of coronary heart disease: a meta-analysis JAMA 2002;288:2023-2031.
This same post, written for patients, can be found at http://clotconnect.wordpress.com/2010/11/13/unexplained-arterial-clots-%e2%80%93-causes-thrombophilia-testing/
Disclosure: I have no financial conflict of interest relevant to this blog entry.
Last updated: Jan 16th, 2013