<unk>  can be congenital or acquired. Congenital<unk>  refers to inborn conditions (and usually hereditary, in which case "hereditary<unk> " may be used) that increase the tendency to develop thrombosis, while, on the other hand, acquired<unk>  refers to conditions that arise later in life. Congenital The most common types of congenital<unk>  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<unk>  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<unk> s 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 resulting from acquired alterations in the PIGA gene, which plays a role in the protection of blood cells from the complement system. PNH increases the risk of venous thrombosis but is also associated with hemolytic anemia (anemia resulting from destruction of red blood cells). Both HIT and PNH require particular treatment. Hematologic conditions associated with sluggish blood flow can increase risk for thrombosis. For example, sickle-cell disease (caused by mutations of hemoglobin) is regarded as a mild prothrombotic state induced by impaired flow. Similarly, myeloproliferative disorders, in which the bone marrow produces too many blood cells, predispose to thrombosis, particularly in polycythemia vera (excess red blood cells) and essential thrombocytosis (excess platelets). Again, these conditions usually warrant specific treatment when identified. Cancer, particularly when metastatic (spread to other places in the body), is a recognised risk factor for thrombosis. A number of mechanisms have been proposed, such as activation of the coagulation system by cancer cells or secretion of procoagulant substances. Furthermore, particular cancer treatments (such as the use of central venous catheters for chemotherapy) may increase the risk of thrombosis further. Nephrotic syndrome, in which protein from the bloodstream is released into the urine due to kidney diseases, can predispose to thrombosis; this is particularly the case in more severe cases (as indicated by blood levels of albumin below 25 g/l) and if the syndrome is caused by the condition membranous nephropathy. Inflammatory bowel disease (ulcerative colitis and Crohn's disease) predispose to thrombosis, particularly when the disease is active. Various mechanisms have been proposed. Pregnancy is associated with an increased risk of thrombosis of 2- to 7-fold. This probably results from a physiological hypercoagulability in pregnancy that protects against postpartum hemorrhage. This hypercoagulability in turn is likely related to the high levels of estradiol and progesterone that occur during pregnancy. Estrogens, when used in combined hormonal birth control and in menopausal hormone therapy (in combination with progestogens), have been associated with a 2- to 6-fold increased risk of venous thrombosis. The risk depends on the types of hormones used, the dose of estrogen, and the presence of other<unk>  risk factors. Various mechanisms, such as deficiency of protein S and tissue factor pathway inhibitor, are said to be responsible. Obesity has long been regarded as a risk factor for venous thrombosis. It more than doubles the risk in numerous studies, particularly in combination with the use of oral contraceptives or in the period after surgery. Various coagulation abnormalities have been described in the obese. Plasminogen activator inhibitor-1, an inhibitor of fibrinolysis, is present in higher levels in people with obesity. Obese people also have larger numbers of circulating microvesicles (fragments of damaged cells) that bear tissue factor. Platelet aggregation may be increased, and there are higher levels of coagulation proteins such as von Willebrand factor, fibrinogen, factor VII and factor VIII. Obesity also increases the risk of recurrence after an initial episode of thrombosis. Unclear A number of conditions that have been linked with venous thrombosis are possibly genetic and possibly acquired. These include: elevated levels of factor VIII, factor IX, factor XI, fibrinogen and thrombin-activatable fibrinolysis inhibitor, and decreased levels of tissue factor pathway inhibitor. Activated protein C resistance that is not attributable to factor V mutations is probably caused by other factors and remains a risk factor for thrombosis. There is an association between the blood levels of homocysteine and thrombosis, although this has not been reported consistently in all studies. Homocysteine levels are determined by mutations in the MTHFR and CBS genes, but also by levels of folic acid, vitamin B6 and vitamin B12, which depend on diet.
Thrombophilia
Exophilia
Basophilia
Dysfibrinogenemia
Hyperprothrombinemia
Giant platelet disorder
Hypodysfibrinogenemia
Hypoprothrombinemia