Term
| What's the difference between hemostasis and thrombosis? |
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Definition
| thrmobosis is a pathological extension of normal hemostasis. Hemostasis is the arrest of hemorrhage in response to a vascular injury. Thrombosis is a formation of a blood clot in circulation |
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Term
| What immediately causes a blood clot? (not the whole cascade, just the last step) |
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Definition
| soluble plasma protein fibrinogen is converted to an insoluble fibrillar polymer, fibrin. This reaction is catalyzed by the proteolytic enzyme, thrombin |
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Term
| What is primary hemostasis? |
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Definition
| when injury exposes subendothelial collagen which surves as a nidus for thrombus generation. Platelets adhere and are activated and then attract other platlets to form initial hemostatic plug. |
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Term
| What is secondary hemostasis? |
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Definition
| When release of tissue factor (factor 3 or thromboplastin) at the site of injury activates plasma coagulation sequence which results in the formation of thrombin fibrin and attracts more platelets |
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Term
| What causes vasoconstriciton when a vessel is injured? |
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Definition
| neurogenic mechanisms and/or locally released humoral factors (endothelin) |
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Term
| T/F Endothelium helps regulate hemostasis. |
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Definition
| True! the endothelial cells exert both antithrombotic and prothrombotic effects that helps maintian the balance |
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Term
| What are the antiplatelet effects of the endothelium? |
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Definition
| 1) provide intact barrier from subendothelial collagen 2) produces PGI2 and NO which inhibit platelet aggregation and cause vasodilation |
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Term
| What causes endothelial cells to produce PGI2 and NO? |
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Definition
| ADP, thrombin, and cytokines (this prevents platelets from adhering to normal endothelium adjascent to damaged endothelium |
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Term
| What are the anticoagulant properties of endothelial cells? |
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Definition
| membrane associated heparin-like molecules such as thrombomodulin (thrombin inhibitor) and tissue factor pathway inhibitor |
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Term
| What are the fibrinolytic properties of endothelial cells? |
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Definition
| synthesize tissue type plasminogen activators (t-PA) that promote fibrinolysis |
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Term
| What are the prothrombotic properties of endothelial cells? |
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Definition
| they synthesize and secrete vWF, can be induced by cytokines or endotoxins to make tissue factor to activate the extrinsic clotting pathway, express binding sites for activated clotting factors, makes inhibitor of t-PA |
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Term
| Does overt activation of endothelium overall favor thrombic or antithrombic effects? |
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Definition
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Term
| What are the two granules of platelets? |
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Definition
| alpha granules and electrone dense bodies |
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Term
| What's in alpha granules of platelets? |
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Definition
| fibrinogen, fibronectin, factors V, VIII, platelt factor 4 and growth factors (PDGF and TGF-B) |
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Term
| What's in electron dense bodies? |
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Definition
| ADP, ATP, Ca, histamine serotonin, and epinephrine |
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Term
| How do platelets adhere on torn endothelium? |
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Definition
| von willebrand factor on torn endothelium binds to glycoprotein Ib on platelets |
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Term
| What is the most common congenital bleeding disorder? |
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Definition
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Term
| What is Bernard-Soulier disease? |
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Definition
| defect in glycoprotein Ib resulting in defective platelet adhesion. Aka giant platelet syndrome because it can be identified on peripheral smears by presence of platelets 2-4x normal size. |
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Term
| What happens when platelet are activated? |
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Definition
| they secrete granules that help coagulatin (calcium and ADP) and a phospholipid complex becomes activated which binds factors that activate the intrinsic pathway of clotting. |
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Term
| T/F Dense body deficiency and gray platelet syndrome are more severe than defects in adherence or aggregation. |
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Definition
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Term
| What three important stimuli convert a temporary plug to a secondary plug? |
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Definition
| ADP (dense granules), TxA2 (from activated platelets), and thrombin (from activation of coagulation cascade) |
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Term
| How does thrombin contribute to formation of a secondary plug? |
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Definition
it binds to protease activated receptor ona platelet and with ADP and TxA2 causes further aggregation/platelt contraction
Also, it converts fibrinogen to fibrin which stabalizes the hemostatic plug |
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Term
| What is Glanzman's thrombasthenia? |
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Definition
| lack of glycoprotein IIv-IIIa on platelet membrane which is the site of fibrinogen binding. Result is a lack of platelet aggregation in reponse to ADP, collagen or thrombin. Autosomal recessive transmission |
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Term
| What activates antithrombins? |
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Definition
| binding to heparin-like molecules on endothelial cells and by binding therapeutic heparin |
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Term
| Heparin inhibits what molecules? |
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Definition
| thrombin and other proteases |
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Term
| How is protein C activated? |
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Definition
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Term
| What do proteins C and S do? |
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Definition
| they are vitamin K dependent and inactivate cofactors which accelerate coagulation cascade |
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Term
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Definition
| tissue factor pathway inhibitor |
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Term
| How is plasminogen converted to plasmin? |
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Definition
| via factor XII dependent pathway or via plasminogen activators like urokinase, tissue type PA (t-PA) streptokinase (bacterial product) |
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Term
| What inhibits fibrinolysis? |
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Definition
| PAI and alpha2-antiplasmin |
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Term
| How does production of IL-1 and TNFalpha favor thrombus formation? |
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Definition
| they stimulate t-PA inhibitor |
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Term
| Name some common "clot busters" used clinically as therapeutic. |
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Definition
| t-PA, urokinase, and streptokinase |
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Term
| T/F A thrombus is by definition adherent to the vascular endothelium |
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Definition
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Term
| Name the there major factors that contribute to development of a thrombosis, which are known as Virchow's Triad. |
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Definition
| 1) vascular lesions/endothelial injury 2) decreased/altered blood flow 3) hypercoagulability |
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Term
| What causes most arterial thromboses? |
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Definition
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Term
| T/F Most arterial thrombi are occlusive. |
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Definition
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Term
| Incomplete vessel occlusion leads clinically to ________ in the heart or ______ in the brain. |
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Definition
| angina pectoris, transient cerebral ischemic attacks (TIAs) |
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Term
| Arterial thromboses are driven and mediated by ____. |
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Definition
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Term
| A thrombosis formed along the wall of a ventricle in the heart is called a _________. |
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Definition
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Term
| What clinical conditions are associated with formation of a mural thrombus? |
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Definition
| MI, a fib, cardiomyopathy, endocarditis |
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Term
| T/F Most venous thrombi are occlusive |
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Definition
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Term
| Where are most venous thromboses found? |
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Definition
| in the lower legs (deep calf, femoral, popliteal, iliac) or the ovarian veins of women |
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Term
| Venous thrombi are often called coagulative or stasis throbi due to the... |
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Definition
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Term
| What does factor 5 Leiden mutation cause? |
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Definition
| activated protein C resistance. This favors thrombosis and is in 3-15% of caucasians in heterozygous form |
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Term
| What are common aquired abnormalities leading to thrombosis? |
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Definition
| anticardiolipid antibodies in lupus anticoagulant (antiphopholipid antibody syndrome) and HIT (heparine induced thrombocytopenia) |
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Term
| What do you call it when a blood clot gets larger due to increased platelets and fibrin? |
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Definition
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Term
| What happens to clots that persist for more than a few days on the vascular surface? |
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Definition
| they become covred with endothelial cells and there is aningrowth of granulation tissue, smooth muscle, and mesenchymal cells into the thrombus. Capillaries can anastomose and restore some of the lumen ("recanalization") |
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Term
| Most arterial emboli arise from a thrombus located in the ___ and get lodged in the ____________. |
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Definition
| heart; lower extremeties (70-75%) or brain (10%) |
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Term
| T/F Most pulmonary emboli are clinically silent. |
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Definition
| true 60-80% remain small enough to not cause symptoms |
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Term
| Obstruction of small pulmonary vessels cause ________. Obstruction of medium sized pulmonary vessels cause _______. |
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Definition
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Term
| What are the signs of a PE? |
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Definition
| transient dyspnea and tachypnea. Pulmonary infarction with pleuritic chest pain, hemoptysis, and pleural effusion. Cardiovascular collapse with sudden death |
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Term
| What puts a patient at risk for a fat embolism? |
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Definition
| trauma. 90% of patients with severe skeletal injuries will have fat emboli <10% will have clinical findings (tachypnea, dyspnea, anemia, neurologic symptoms) |
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Term
| Nearly all infarcts result from.. |
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Definition
| thromboembolic events and arterial occlusion |
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