in which case "hereditary thrombophilia" may be used) that increase the tendency to develop thrombosis, while, on the other hand, acquired thrombophilia refers to conditions that arise later in life. Congenital The most common types of congenital thrombophilia are those that arise as a result of overactivity of coagulation factors. They are relatively mild, and are therefore classified as "type II" defects. The most common ones are factor V Leiden (a mutation in the F5 gene at position 1691) and prothrombin G20210A, a mutation in prothrombin (at position 20210 in the 3' untranslated region of the gene). The rare forms of congenital thrombophilia are typically caused by a deficiency of natural anticoagulants. They are classified as "type I" and are more severe in their propensity to cause thrombosis. The main ones are antithrombin III deficiency, protein C deficiency and protein S deficiency. Milder rare congenital thrombophilias are factor XIII mutation and familial dysfibrinogenemia (an abnormal fibrinogen). It is unclear whether congenital disorders of fibrinolysis (the system that destroys clots) are major contributors to thrombosis risk. Congenital deficiency of plasminogen, for instance, mainly causes eye symptoms and sometimes problems in other organs, but the link with thrombosis has been more uncertain. Blood group determines thrombosis risk to a significant extent. Those with blood groups other than type O are at a 2- to 4-fold relative risk. O blood group is associated with reduced levels of von Willebrand factor – because of increased clearance – and factor VIII, which is related to thrombotic risk . Acquired A number of acquired conditions augment the risk of thrombosis. A prominent example is antiphospholipid syndrome, which is caused by antibodies against constituents of the cell membrane, particularly lupus anticoagulant (first found in people with the disease systemic lupus erythematosus but often detected in people without the disease), anti-cardiolipin antibodies, and anti-β2-glycoprotein 1 antibodies; it is therefore regarded as an autoimmune disease. In some cases, antiphospholipid syndrome can cause arterial as well as venous thrombosis. It is also more strongly associated with miscarriage, and can cause a number of other symptoms (such as livedo reticularis of the skin and migraine). Heparin-induced thrombocytopenia (HIT) is due to an immune system reaction against the anticoagulant drug heparin (or its derivatives). Though it is named for associated low platelet counts, HIT is strongly associated with risk of venous and arterial thrombosis. Paroxysmal nocturnal hemoglobinuria (PNH) is a rare condition