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|What are the major coagulation inhibitors?
|TFPI - inhibit 7a + TF Protein C - inhibit 5a + 7a Antithrombin - 9a, 10a, 2a
|What is a Hereditary Thrombosis Syndrome (HTS)?
|*Autosomal dominant* disorders that lead to hypercoagulability. Patients may have DVT and pulmonary emboli at a young age. Thrombosis can occur at young age as well.
|Describe Factor V Leiden Mutation.
|Most common type of HTS where Factor V is mutated. This prevents them from being inactivated by protein C -> Excess of activated Factor V This disease alone isn't too severe, but may become severe if mixed with other conditions.
|Describe the Protein C/S Deficiency.
|Defect in proteins that help to stop coagulation -> Can't stop thrombin formation Very high risk of thrombosis -> Needs anticoagulation immediately
|Describe Antithrombin III Deficiency
|Mutation that results in reduced acitivty of ATIII, which is an inhibitor of each of the activated coagulation cascade enzymes, primarily factors IIa and Xa.
|What diseases are covered in HTS?
|Factor V Leiden Mutation, Protein C/S Deficiency, Antithrombin III Deficiency
|How do you treat Protein C/S Deficiency?
|You start with Heparin first THEN slowly add Warfarin. If you start with Warfarin, you may get Warfarin Skin Necrosis, because Protein C level drops to 0.
|Compare mechanism of Heparin vs. Warfarin.
|Warfarin prevents Vitamin K reductase -> Prevents Vit. K Dependent enzymes from working Heparin increases activity of Antithrombin III -> Prevents clots from happening, but does NOT remove clots already formed
|How do you treat Antithrombin III Deficiency?
|You give them HIGH dose of Heparin followed by Warfarin. Regular dose of heparin will not work!
|What are some molecules secreted by the endothelium to prevent clotting? Describe the functions.
|1) Heparin-like Molecules (HLM) -> activates antithrombin III 2) tPA -> Enzyme that converts plasminogen to plasmin. 3) Thrombomodulin - modulates thrombin for it to activate protein C
|What is Plasmin's function?
|Plasmin breaks down fibrin, serum fibrinogen, coagulation factors, and blocks platelet aggregation.
|What are some diseases that cause endothelial damage?
|Atherosclerosis, Vasculitis, Cystathione beta synthase (CBS) deficiency, and build-up of homocysteine
|What is CBS deficiency?
|a disorder when levels of Cystathione Beta Synthase (an enzyme that converts homocysteine to cystathione) is low. Causes build-up of homocysteine, which damages endothelium.
|Why does oral contraceptives increase the risks of thrombosis?
|Oral contraceptives contains estrogen -> Estrogen increases production of coagulation factors -> Increase risk of thrombosis
|What happens in Prothrombin G20210A Mutation?
|Mutation causes Guanine in Prothrombin to turn into Adenine -> this causes activity level of the prothrombin to increase
|Autoimmune disease that causes body to make antibodies against phospholipids. What disease is this?
|Antiphosphopids Syndrome (Lupus Anticoagulant)
|Features of Antiphospholipid Syndrome
|1) Increase in APTT 2) Protein C/S are deficient b/c they are attacked.
|How does cancer increase the risk of thrombosis?
|Increases the production of Tissue Factor + increases platelet activation and division.
|Describe Heparin Induced Thrombocytopenia
|Heparin can bind to PF4 -> the PF4+heparin complex (called Hapten) is recognized as foreign antigen -> Immune system response activates platelets -> constant activation leads to depletion