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Problems with coagulation cascade regulation
- Activated Protein C resistance (virtually always caused by the Factor V Leiden mutation -a mutation in the gene that makes the factor V protein). Factor V is activated normally, but it is resistant to degradation by activated Protein C, which regulates the clotting process.
- 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 deficiency or dysfunction - Protein C helps regulate the speed of the coagulation cascade by degrading activated factors V and VIII.
- Protein S deficiency or dysfunction - Protein S is a cofactor with Protein C
- Prothrombin G20210A mutation - a mutation that results in an increased amount of thrombin (activated factor II) in the circulation, which is associated with an increased risk for blood clots.
- Elevated factor VIII levels - persistently elevated factor VIII levels that are not associated with inflammation or other acquired conditions but are associated with an increased thrombotic risk.
- Antiphospholipid syndrome (lupus anticoagulant and anticardiolipin antibody)
- Disseminated intravascular coagulation (DIC)
- Bone marrow disorders such as myeloproliferative disorders
- In very rare cases, antibodies to coagulation factors; most factor antibodies cause bleeding episodes, not clotting problems.
- Systemic lupus erythematosus - an autoimmune disorder