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Thrombotic Disorders
| Question | Answer |
|---|---|
| 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
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