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20 Cards in this Set
- Front
- Back
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Haemostasis
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the stopping of blood loss from damaged vessels and protect against haemorrhage. A highly complex, regulated process
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Mechanisms involved in haemostasis
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Vasoconstriction
Platelet adhestion to the exposed tissue Platelet activation to form a haemostatic plug Reinforcement of plug by fibrin |
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Thrombosis
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The formation of blood clots where they shouldn't occur
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What are the predisposing factors (Virchow’s triad)
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Injury to the vessel wall
Altered blood flow increased coagulability of the blood |
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Contrast venous and arterial thrombi
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venous: red clots, mainly erythrocytes and fibrin
arterial thrombi: white clots, predominantly platelet aggregates |
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How are platelets activated
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when damage occurs to blood vessels, exposing the endothelial collagen. The endothelial layer controls blood flow by secreting mediators that have an effect on underlying smooth muscle cells, platelets are only activated when they adhere to collagen.
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How do activated platelets form a platelet plug
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When the platelets are activated, they release messengers ADP and thromboxane A2 that recruits more platelets in a positive feedback loop to create the platelet plug.
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Why is prostacyclin and NO secreted during this process
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After this plug is created prostacyclin and NO are released to inhibit platelet aggregation to insure the clotting only occurs at the site of injury
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Antiplatelet drugs are used to treat arterial thrombosis such as
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acute myocardial infarction, Coronary Artery Bypass Graft or CABG, transient ischemia or for high risk patients of myocardial infarction
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Arachidonic Acid (AA)
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released from phospholipids by PLA2, which is then catalytically converted into a series of biologically active metabolites (eicosanoids)
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The three major pathways for eicosanoid production
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cyclooxygenases, lipoxygenases and epoxygenases
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Why is cyclooxygenease (COX) important in platelet function
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causes the formation of endoperoxides like PGG2 and PGH2, which are then further converted to prostacyclin, epoprostenol and thromboxane
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Mechanism of thrombaxine and prostacyclin
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prostacyclin binds to IP receptors, which increase cAMP. While thromboxane increases platelet activation by binding to TP receptors which increases Ca2+
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Role of aspirin in platelet function
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inhibits COX1 by acetylating the active site in an irreversible step. Therefore, preventing the formation downstream products such as thromboxane and prostacyclin
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how does it act as an antiplatelet drug if it reduces prostacyclin production
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when aspirin affects the COX enzymes in nucleated endothelial cells, they can just make more and therefore keep producing inhibitory Prostacyclin.
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How does ADP activate more platelets
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binds to purinergic (P2Y) receptors present on platelets, which activate them
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Clopidogrel
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A thienopyridine that irreversibly inhibit P2Y12 receptors through a disulfide bond. Hence it is an antagonist for ADP
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Glycoprotein IIb/IIIa inhibitors
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inhibit glycoprotein integrins from binding to fibrinogen and aggregating platelets.
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Protease-activated receptors
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subclass of GPCRs that self activate instead of ligand activated receptors.
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Protease-activated receptors in platelet function
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Activated by thrombin cleaving the inactive N-terminus of PAR1 and PAR4, and the conformational change is now an activated N-terminus tethered ligand, which initiates a signalling cascade that activates the platelets. Phosphorylation of the intracellular domain desensitises the receptor
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