Hereditary Thrombophilia

Hereditary Thrombophilia

Overview

Thrombophilia is a group of disorders affecting the blood coagulation. It is characterized by an increased tendency to form blood clots. Consequently, a higher incidence of venous thrombosis and thromboembolic events is associated with this disease. This is also known as a hypercoagulable condition and/or a prothrombotic state.(1)

Trombosis is the abnormal formation of a blood clot in a blood vessel. The clot then causes an obstruction of blood flow. Physiologically, blood clots are our body's way of stopping bleeding when a blood vessel is damaged. Once the injury heals, the thrombus dissolves and everything returns to normal. In thrombophilia, either clots form at a higher rate or there is no dissolution of those that have already formed.(2)

Thromboembolic events describe a situation where a thrombus is dislodged from the site of origin into the body's circulation and clogs another blood vessel, which can affect various organs, causing damage and even result in death. These include, for example, pulmonary embolism or stroke.

Thrombophilia may be either acquired during life or inherited. The most frequent conditions are listed in the table below. As for acquired forms, the listed factors are known to increase the risk of blood clotting. This however does not mean that everyone who undergoes surgery or is overweight will develop thrombosis because of it. 

Table 1: Causes of thrombophilia

Prevalence & Risk factors

It is believed that a substantial proportion of the population has a thrombophilic mutation, but in most of them the presence of another risk factor is required for the development of thrombosis.(3)

The prevalence of thrombophilic mutations differs significantly worldwide. 

Thrombophilia risk factors include:

   

Genetics

Genetic information is inherited in pairs, because every gene has two copies, each from one of the parents. The most common inheritance pattern in thrombophilia is autosomal dominant, which means that to have an active form of the disease, a person only needs to have a mutation in one of the copies. If both copies are affected, the risk of thrombosis increases even more. The same can be said for those who inherit thrombophilic mutations in more than one gene.(5)

The inheritance pattern for thrombophilia can be autosomal dominant, autosomal recessive or X-linked, depending on the gene in question. The most common genes involved are the F5 gene for Factor V Leiden thrombophilia and the G20210A point mutation in the prothrombin gene.(1)

Signs & Symptoms

In some people the condition remains dormant their entire life and they never experience thrombosis. In others, blood clots can form in various organs and cause a wide range of symptoms depending on the location.

Diagnosis

The diagnosis of thrombophilia is often made after the first symptoms appear and the patient seeks medical attention. To diagnose thrombophilia, several tests and methods may be used:

  • Family and personal clinical history
  • Physical examination
  • Blood tests
  • Imaging - X-ray, CT, ultrasound
  • Genetic testing

Therapy

To date, there is no specific treatment for thrombophilia, except in cases where it is an acquired form due to another disease. However, there are medications which can either be used to dissolve the blood clot in acute states (thrombolytics) or lower the probability of its formation if taken on a regular basis (blood thinners such as heparin, warfarin or new oral anticoagulant drugs). When prescribing blood thinners, it is always necessary to assess the benefits and risks associated with the treatment. The biggest risk is significant bleeding.(2)

Prevention

There are several ways to prevent thrombophilia and lower the risk of thrombosis: (2)

  • Physical movement of the body (during long transports when traveling, after surgery, after illness, etc.)
  • Hydratation
  • Regular exercise
  • Maintain a healthy weight
  • Quit smoking
  • Follow a healthy diet
  • Pay attention to your other medical conditions, which can increase the risk of thrombosis
  • Appropriate cancer screenings

Prognosis

The risk of thrombosis (and hence the prognosis) varies according to the  underlying condition. It also increases significantly with each risk factor present (acquired or inherited). This is why many people with thrombophilia never develop a dangerous blood clot, while others may have a life-threatening condition.Protein S deficiency, protein C deficiency and antithrombin deficiency are far less common but associated with higher risk of venous thrombosis.(6)

Recommendations

  • If you are overweight, try to lose weight. Even a small weight loss can be beneficial. 
  • Follow a heart-healthy diet rich in fruits, vegetables, and low-fat dairy products, and low in meats, sweets, and refined grains.
  • Stay hydrated.
  • Try to include regular exercise in your daily life. 
  • Do not smoke.

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Recommendations

  • If you are overweight, try to lose weight. Even a small weight loss can be beneficial. 
  • Follow a heart-healthy diet rich in fruits, vegetables, and low-fat dairy products, and low in meats, sweets, and refined grains.
  • Stay hydrated.
  • Try to include regular exercise in your daily life. 
  • Do not smoke.

Sources

  1. Dautaj, A., Krasi, G., Bushati, V., Precone, V., Gheza, M., Fioretti, F., Sartori, M., Costantini, A., Benedetti, S., & Bertelli, M. (2019). Hereditary thrombophilia. Acta bio-medica : Atenei Parmensis, 90(10-S), 44–46. https://doi.org/10.23750/abm.v90i10-S.8758
  2. Thrombophilia: Causes, Symptoms and Treatment. (n.d.). Retrieved May 5, 2022, from https://my.clevelandclinic.org/health/diseases/21797-thrombophilia
  3. Heit J. A. (2007). Thrombophilia: common questions on laboratory assessment and management. Hematology. American Society of Hematology. Education Program, 127–135. https://doi.org/10.1182/asheducation-2007.1.127
  4. Hereditary antithrombin deficiency: MedlinePlus Genetics. (n.d.). Retrieved May 11, 2022, from https://medlineplus.gov/genetics/condition/hereditary-antithrombin-deficiency/#frequency
  5. The Genetics of Thrombophilia - Blood Clots. (n.d.). Retrieved May 11, 2022, from https://www.stoptheclot.org/news/the-genetics-of-thrombophilia/
  6. Hereditary and Acquired Hypercoagulability: Practice Essentials, COVID-19, Pathophysiology. (n.d.). Retrieved May 13, 2022, from https://emedicine.medscape.com/article/211039-overview#a6
  7. Dautaj, A., Krasi, G., Bushati, V., Precone, V., Gheza, M., Fioretti, F., Sartori, M., Costantini, A., Benedetti, S., & Bertelli, M. (2019). Hereditary thrombophilia. Acta bio-medica : Atenei Parmensis, 90(10-S), 44–46. https://doi.org/10.23750/abm.v90i10-S.8758
  8. Thrombophilia: Causes, Symptoms and Treatment. (n.d.). Retrieved May 5, 2022, from https://my.clevelandclinic.org/health/diseases/21797-thrombophilia
  9. Widimský Petr, Zatloukal Petr, Osmančík Pavel, Moťovská Zuzana, Gregor Pavel, Kočka Viktor, Línková Hana, & Pauk Norbert. (n.d.). Elektronické srdce a plíce. Retrieved May 5, 2022, from https://www.lf3.cuni.cz/3LF-1427-version1-el_srdce_a_plice_dil1.pdf

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