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Thrombotic Disorders

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
Created by: soobyung92