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Problems with coagulation cascade regulation
- Factor V Leiden is a condition caused by mutation in Factor 5(FV) gene at position 1691, increasing the risk of Deep Vein Thrombosis (DVT) and Pulmonary Embolism (PE). It is also known as Activated Protein C resistance because the abnormal Factor is resistant to degradation by activated Protein C, which regulates the clotting process. Studies show that around 3-8% of Caucasians have one copy of mutated FV gene (heterozygous) and 1 in 5000 Europeans have 2 copies of this gene mutation (homozygous). Factor V Leiden mutation is rarer in black Africans, Asians, Australian and American natives.
- Prothrombin 20210 mutation is caused by mutation in prothrombin gene (factor II) at position 20210 in 3’ untranslated gene region. This increases the blood tendency to thicken and hence clot formation. This mutation is prevalent in Caucasians
- Antithrombin (formerly called antithrombin III) deficiency or dysfunction - this is a factor that helps decrease the activity of the clotting process by inhibiting factors Xa, IXa, XIa, and thrombin. Inherited or acquired deficiency of antithrombin can lead to a clot formation.
- Protein C, Protein S and Antithrombin deficiencies are inherited but are very rare. Protein C, protein S and Antithrombin are bodies’ natural anticoagulants, keeping the blood in fluid state but if they are low or not function properly it increases the risks of DVT and PE.
- Congenital plasminogen deficiency is a rare congenital disorder. Plasminogen is activated to form plasmin. Plasmin helps break apart the clot's cross-linked fibrin net. Most of these patients have eye problems, but it can affect other organs too.
- Antiphospholipid syndrome (lupus anticoagulant and anticardiolipin antibody)is caused by antibodies developed against phospholipids which are molecules that participate in the coagulation cascade. These antibodies include lupus anticoagulants (LA), anticardiolipin antibodies and antibodies to beta 2 gycoprotein-1. This is considered as an autoimmune condition causing arterial or venous thrombosis, miscarriages in first trimester of pregnancies and may be associated with systemic lupus erythematosus.
- Heparin Induced Thrombocytopenia is a condition where a patient receiving an anticoagulant called heparin produces antibodies against the heparin. These antibodies activate platelets, reducing their number and causing venous or arterial thrombosis.
- Paroxysomal Nocturnal Haemoglobinuria (PNH) results from a mutation in a gene called PIGA. PIGA gene products normally protect red blood cells from complement system. The mutation causes increased thrombosis and haemolytic anaemia due to overactivation of the complement system on the surface of red blood cells.
- Myeloproliferative neoplasms (formerly known as myeloproliferative disorders) result in excess blood cell production, resulting in polycythaemia vera (increased red blood cell production) and essential thrombocythaemia (increased platelet production). This results in an increased risk of thrombosis.
- Disseminated intravascular coagulation (DIC)