What is thrombophilia?
Blood clots are normally very helpful; they block cuts in our blood vessels to prevent us from bleeding out when injured. But this must be tightly regulated, as both too much and too little blood clotting can cause problems. When blood does not clot enough even minor injuries can cause us to bleed excessively, this is called haemophilia. When the blood clots too often or unnecessarily it is called thrombophilia. The word is derived from “thrombus” + “-philia”, literally meaning “an abnormal tendency to for a thrombus, or clot”.
How is it caused?
As thrombophilia is a collection of conditions it can be caused by many different things, some hereditary and some acquired. The inherited form is thought to be more common, as 70% of thrombophilia patients have a known inherited genetic risk factor (1).
People with inherited thrombophilia are born with the condition, though they may not know it till later in life. The most common cause of inherited thrombophilia is a mutation in the Factor V protein called Factor V Leiden – in Europe and the US 3-8% of the population carry one copy of the mutation and 1/5,000 people carry two copies (we inherit two copies of the gene, one from each parent) (2). The second most common genetic cause is mutations in prothrombin, which occur in 1.7-3% of the population (2). Both Factor V and prothrombin are proteins found in our blood; Factor V converts prothrombin into activated thrombin, which forms blood clots. So a reduction in Factor V activity or an increase in prothrombin can both cause increased clotting.
Acquired thrombophilia is not present at birth but develops later from a variety of causes. These include antiphospholipid syndrome (APS) (3), human immunodeficiency virus (HIV) (4), heparin-induced thrombocytopenia (HIT) (5), oral contraceptive use (6), or metastasized cancers (7).
What are the risk factors?
In general, additional risk factors include anything that would normally increase your risk of developing a blot clot. This includes, but is not limited to; being born male, diabetes, obesity, smoking, inflammatory bowel disease, oral contraceptives, hormonal replacement, long-haul flights, SARS-CoV-2 infection, chronic congestive heart failure, respiratory failure, trauma and fractures, blood transfusion, pregnancy, immobilization, surgery, autoimmune diseases, and cancer (8).
What are the symptoms?
Thrombophilia itself does not have any observable symptoms as it is a tendency to cause blood clots, not the blood clot itself. As thrombophilia increases your risk of deep vein thrombosis (DVT) in the leg and pulmonary embolism in the lungs, patients should be aware of those symptoms (9, 10).
If you have symptoms of a DVT you should contact your doctor urgently or go to a walk-in clinic. The symptoms are normally found in one leg but can affect other areas;
· swollen veins that are painful to the touch,
· swelling in the affected area,
· throbbing or cramping pain in the affected area,
· warm skin around the area,
· and red or darkened skin around the area.
If you have symptoms of a pulmonary embolism, call the emergency services or go to the hospital immediately. The symptoms of a pulmonary embolism are;
· severe difficulty breathing,
· heart beating very fast,
· passing out,
· dry cough or coughing up blood,
· pain in the upper back,
· chest pain.
The effects of thrombophilia can vary significantly; some people have multiple thrombotic events from a young age and some may never have symptoms or even know they have the condition.
How is it diagnosed?
People with thrombophilia are often diagnosed after repeated blood clots or through screening after a close relation has been diagnosed. Diagnosis, however, does not always affect treatment or clinical outcomes, so some professionals advise that testing should be conducted only in very specific cases (11, 12, 13).
In some cases, diagnosis could be highly beneficial, especially for those with other risk factors or medical considerations. For example, thrombophilia has been associated with high risk pregnancies, loss, premature births and fetal growth problems, and so monitoring and preventative care has a clear benefit to people who are, or are planning to become, pregnant (14, 15). On the other hand, diagnosis where there are no additional risks, for example in otherwise healthy individuals, can cause significant patient anxiety, medical discrimination, unnecessary medical intervention, expensive changes to medical insurance, and raise issues with family genetic testing (16).
Thrombophilia is normally diagnosed by a blood test. For the inherited condition this can include genetic testing for the known mutations. For the acquired conditions, the blood sample is tested for time it takes to clot (17).
How is it treated and what is the prognosis?
Thrombophilia itself is managed by reducing the risk of blood clots and most people with the condition will not need medical intervention. Where possible, life style habits can be monitored or changed to reduce the risk, such as weight loss where appropriate, stopping smoking, maintaining a healthy balanced diet, wearing compression socks and regularly walking around during flights, staying hydrated, exercising regularly, and avoiding certain oral contraceptives and hormone replacement therapies. Some individuals may require medical therapies to prevent clots, either on a daily basis or for a specific event, such as pregnancy, flying or surgery. In general, this will involve taking preventative anticoagulants or blood thinners, such as heparin, enoxaparin, warfarin or rivaroxaban. If a clot does occur, it will also be treated with anticoagulants in the same manner and may require surgery to remove the clot (18, 19, 20). Thrombophilia can be easily and successfully managed with proper care – nearly 90% of people with thrombophilia never get a clot (20).
Key points:
· Thrombophilia is a condition where the blood is more prone to clotting
· It can be inherited or acquired later in life
· It is diagnosed via a blood test
· There may be no symptoms of thrombophilia itself, but if you notice symptoms of a blood clot seek medical attention urgently
· It is treated by life style changes and preventative anticoagulants
· Whilst a potentially serious condition, most people have no ill-effects from the condition
References:
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Kujovich JL. GeneReviews. Seattle (WA): University of Washington, Seattle; 2018. Factor V Leiden thrombophilia.
Neto NSR, Strunz CC and de Carvalho JF, 2021. Prevalence of genetic thrombophilia in primary antiphospholipid syndrome. European Review for Medical and Pharmacological Sciences: 25 (10): 3645-3646
Bibas M, Biava G and Antinori A, 2011. HIV-associated venous thromboembolism. Mediterranean Journal of Hematology and Infectious Diseases: 3 (1): e2011030
Armstrong EM, Bellone JM, Hornsby LB, Treadway S and Phillippe HM, 2014. Acquired Thrombophilia. Journal of Pharmacy Practice: 27 (3): 234-242
Bloemenkamp KW, Rosendaal FR, Buller HR, Helmerhorst FM, Colly LP and Vandenbroucke JP, 1999. Risk of venous thrombosis with use of current low-dose oral contraceptives is not explained by diagnostic suspicion and referral bias. Archives of Internal Medicine: 159 (1): 65–70
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Wu O, Robertson L, Twaddle S, Lowe GDO, Clark P, Greaves M, Walker ID, Langhorne P, Brenkel I, Regan L and Greer I, 2006. Screening for thrombophilia in high-risk situations: systematic review and cost-effectiveness analysis. The Thrombosis: Risk and Economic Assessment of Thrombophilia Screening (TREATS) study. Health Technological Assessment: 10: 1-110
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