Thrombosis in both arteries and veins is a unique clinical scenario. Arterial and venous thrombosis are associated with several known risk factors, while other cases are idiopathic. Most known causes of thrombophilia are related to venous thromboembolic events, but there are several hypercoagulable conditions that cause both arterial and venous thrombosis. An easy way to look at these causes is by dividing them into hematological, systemic and local diseases.
Hematological causes for arterial and venous thrombosis
- Antiphospholipid antibodies – Antiphospholipid antibodies can be reactive or part of an autoimmune syndrome, either isolated or as part of a more complex disease such as systemic lupus erythematosus. Antiphospholipid antibodies are a general name for a group of antibodies that also includes anticardiolipin and beta-2 microglobulin, among others.
- Hyperhomocysteinemia – Elevated levels of plasma homocysteine levels correlate with accelerated atherosclerosis and thus with arterial thrombosis. Hyperhomocysteinemia also correlates with venous thromboembolism. While homozygotes tend to have a very increased risk, heterozygotes have lower levels of homocysteine and their risk for thrombosis is not as high. A mutation in methylenetetrahydrofolate gene (MTHFR) is responsible for the pathology. Serum levels of more than 15 micromol/liter are associated with an increased risk for myocardial infarction. Vitamin B12 and folic acid supplementation can reduce the serum levels of homocysteine. This has not been proven to reduce risk, though. A trial examining vitamin B12 and folic acid supplements for secondary prevention in over 12000 patients did not find reduced cardiovascular risk, while revealing increased cancer risk.
- Heparin induced thrombocytopenia (HIT) – Heparin induced thrombocytopenia in itself is not a cause of venous thrombosis, but rather of arterial thrombosis. However, patients with venous thrombosis may present with arterial thrombosis while being treated with heparin and the cause will be HIT.
Other than inherited and acquired thrombophilia there are various local and systemic disease states that need to be considered when arterial and venous thrombosis are encountered.
Non-hematological causes of arterial and venous thrombosis
- Paradoxical emboli – A venous clot that ends up in the arterial circulation is termed a paradoxical embolus. In order for this to happen a connection between the right and left sides of the heart needs to exist. Usually this is a patent foramen ovale. Diagnosis is preliminarily made by echocardiogram with bubbles showing the shunt.
- Popliteal artery aneurysm – a popliteal artery aneurysm, when large enough, can cause compression on the adjacent popliteal vein and thus a DVT may form. Furthermore, the major presenting problem with popliteal artery aneurysms are distal emboli. Therefore, a popliteal aneurysm may present with distal emboli and a popliteal vein thrombosis.
- Cancer – Malignancy correlates to superficial vein thrombosis, deep vein thrombosis and arterial thrombosis. Patients with cancer (occult or overt) tend to have a higher recurrence rate of venous thromboembolism, more widespread clots and more failure of treatment. Read more about cancer and venous thromboembolism.
- Bechet’s disease – Bechet’s disease is characterized by mouth and genital ulcers, skin phenomena including erythema nodosum and pathergy phenomenon and uveitis. Bechet’s patients also have arterial aneurysms that are often in unusual locations such as the pulmonary and splenic arteries.
- Thromboangiitis obliterans (Buerger’s disease) – The arterial disease is typically distal. The venous thrombosis is typically superficial.
- Paroxysmal nocturnal hemoglobinuria
- Nephrotic syndrome – the connection between nephrotic syndrome and both arterial and venous thrombosis has been known for many years. Venous thrombosis is more common in nephrotic syndrome than arterial thrombosis and is secondary to loss of anticoagulants in the urine including antithrombin III. A recent analysis published in Circulation in 2008 repeated these findings and found that nephrotic syndrome correlated with arterial and venous thrombosis.
Read more about arterial and venous thrombosis
- The role of thrombophilia in both veins and arteries. Annals of internal medicine. 1997.