A hypercoagulable disorder, also known as thrombophilia, is an inherited or acquired condition that increases the risk of inappropriate or excessive thrombus (blood clot) formation.
Clotting is a normal response to blood vessel or tissue injury. When a blood vessel is injured, it begins to leak blood, either externally or into body tissues. The body stops this blood loss through a complex clotting process called haemostasis. During haemostasis, the injured blood vessel constricts to reduce blood flow, platelets adhere to the injury site and clump together to form a loose platelet plug and the coagulation cascade is initiated. During the cascade process, the body sequentially activates coagulation factors, proteins that create a net of fibrin threads, weave them through the platelet plug and stabilise the resulting blood clot. This clot functions as a barrier to further blood loss, one that stays in place until the injury has healed.
Usually, the body activates the clotting process, regulates its speed and volume with feedback mechanisms, and after the site has healed, breaks down the clot and removes it. Hypercoagulable disorders occur when something goes wrong with the clotting process. If the process activates inappropriately, does not self regulate properly, or resists being broken down, then there can be inappropriate and/or excessive blood clot formation.
Blood clots are referred to as thrombi (one – thrombus) when they form in a blood vessel; thrombi may break off and block another blood vessel in another part of the body, where they are referred to as emboli (one – embolus).
- Venous thromboembolism (VTE) is the most common condition associated with hypercoagulable disorders. It includes conditions like superficial or Deep Vein Thrombosis (DVT) and Pulmonary embolism (PE). DVT is caused by blood clot (thrombosis, plural thrombi) formation in large veins of legs causing redness, pain and swelling particularly at the back of legs below knee. The thrombi may sometimes break (emboli) and travel to other parts of the body through the bloodstream, which is known as embolism. Embolism can be life threatening if the clot travels to the lungs causing PE or to the brain causing strokes
- Thrombosis of unusual venous circulations causes cerebral vein thrombosis (brain), hepatic and portal vein thrombosis (liver), mesenteric vein thrombosis (small intestines), renal vein thrombosis (kidney), venous thrombosis in arms and ovarian vein thrombosis
- Recurrent foetal loss (miscarriages) and other complications in pregnancy may be associated with thrombophilia.
- Pupura fulminas is caused by Protein C deficiency in newborns and even in adults causing tissue death and bleeding under the skin and other organs.
- Warfarin induced skin necrosis is caused by Protein C and Protein S deficiency on commencement of anticoagulant treatment with warfarin.
- Disseminated intravascular coagulation (DIC) is a life-threatening, acute, acquired condition that causes tiny clots throughout the body. It uses up coagulation factors at an accelerated rate, leading to both bleeding and inappropriate clotting.
Certain inherited gene mutations that may predispose someone to hypercoagulable states, such as factor V Leiden or the prothrombin G20210A mutation, are relatively common in the population, but it is thought that they add only a slight increase in the risk of actually developing a problem with clotting. Other inherited hypercoagulable disorders, such as protein C deficiency, protein S deficiency, and antithrombin deficiency have a higher risk of thrombosis but are relatively rare. These are generally due to genetic mutations that lead to a deficiency or dysfunction in the coagulation protein that the gene produces. All of the inherited disorders (except for antithrombin deficiency) may be seen in heterozygous (one gene copy) or homozygous (two gene copies) form. If someone has two mutated gene copies, they tend to have a more severe form of the condition, and if they are heterozygous in more than one condition, the risk of clotting tends to be additive (and sometimes they multiply the risk). With inherited hypercoagulable disorders, the first thrombotic episode may be seen at a relatively young age (less than 40 years of age). The patient may have recurrent thrombosis, a family history of thrombosis, and blood clots in unusual sites (such as cerebral veins, hepatic veins, and renal veins).
Acquired disorders are more commonly known to be the cause of hypercoagulable states than inherited ones. They may be related to antiphospholipid antibodies, liver disease, cancer, surgery or immobilizations. The next few pages describe several hypercoagulable disorders.