Patient Education Blog

Unexplained Arterial Clots – Causes, Thrombophilia Testing

Stephan Moll, MD writes…

Arteries are the blood vessels that lead blood away from the heart into the periphery, i.e. to the extremities, the brain, the abdominal and pelvic organs. They deliver oxygen to organs and muscles. Veins lead the blood back to the heart, from where it flows into the lung to take up fresh oxygen. Blood clots in arteries can lead to stroke (so called ischemic stroke), heart attacks, or gangrene of the extremities. Blood clots in veins are called superficial thrombophlebitis, deep vein thrombosis (DVT), and pulmonary embolism (PE).

Main Causes of arterial clots

There are 2 main reasons why people develop artery occlusions:

  • Arteriosclerosis: Often, blood clots form in arteries narrowed by plaque – deposits of cholesterol and other unwanted materials. This underlying narrowing and hardening of the artery is called arteriosclerosis or atherosclerosis. It typically occurs in people who are overweight, smoke, have high cholesterol, high blood pressure, or diabetes mellitus.
  • Atrial fibrillation: Another common cause for arterial blood clots is an irregular heartbeat, called atrial fibrillation, or “a. fib”. In this medical condition parts of the heart do not contract in a coordinated manner, leading to an increased risk of blood clot formation in one of the heart chambers (called the left atrium). From there, clots can travel with the bloodstream into the brain (causing a stroke), the coronary arteries (causing a heart attack), the abdominal organs (causing infarction [=damage from lack of oxygen delivery] of the intestine, spleen, kidney), or the extremities (causing gangrene).


Only uncommonly do arterial blood clots occur in the middle aged or younger person (less than approximately 50 years of age) who do not have arteriosclerosis or atrial fibrillation. In that case, a number of uncommon conditions, including clotting disorders (=thrombophilias) should then be considered and investigated (see table below).

However, 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 genetic abnormalities (polymorphisms) are not a risk factor for arterial clots 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 the table, and consider doing the thrombophilia work-up listed in the table.

Table. Arterial clots – Causes and work-up

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 clots, 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. The role of a connection (hole) between the right and left chamber of the heart (called PFO = patent foramen ovale) in arterial clots is not fully clear.

Patients with arterial clots due to arteriosclerosis are typically treated with drugs that make platelets slick, so called anti-platelet drugs (aspirin, clopidogrel = Plavix®, Aggrenox®, Prasugrel®). Patients with atrial fibrillation and stroke are typically treated with warfarin (Coumadin®, Jantoven®) or one of  the new “blood thinners” such as Dabigatran (Pradaxa®), Rivaroxaban (Xarelto®), or Apixaban (Eliquis®). Whether individuals with arterial clots who are found to have one of the strong thrombophilias discussed above are more effectively treated with anti-platelet therapy or “blood thinners”, is not known.


  1. 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.
  2. 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.
  3. Klerk M. MTHFR 677C–>T polymorphism and risk of coronary heart disease: a meta-analysis JAMA 2002;288:2023-2031.

Disclosure:  I have no financial conflict of interest relevant to this blog entry.

Last updated: Jan 16th, 2013

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