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26 Cards in this Set
- Front
- Back
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Define Haemostasis
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-The process of maintaining blood fluid in a clot free state
-To be able to induce a rapid localised haemostatic plug at the site of injury |
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What are the 3 main components of Haemostasis?
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-Vascular wall endothelium (anticoagulant lining of blood vessels)
-Platelets -Coagulation Cascade (inactive procoagulants and cofactors) |
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What is the role of endothelin?
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-Released by endothelium at site of vascular injury where it binds to endothelin receptor on smooth muscle causing constriction
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What is involved in primary haemostasis?
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1.Platelet adhesion
2.Chape change 3.Granule Release (ADP, TXA2) 4. Recruitment 5.Aggregation (haemostatic plug) |
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What is Virchow's Triad?
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-Endothelial injury
-Haemodynamic changes (stasis) -Hypercoagulobility |
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What are the steps involved in secondary haemostasis?
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1.Tissue factor released
2.Phospholipid complex expression 3.Thrombin activation (activation of coagulation cascade) 4.Fibrin polymerisation |
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What is the role of the fibrinolysis system?
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Prevents blood clots from growing and becoming problematic
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What are the steps of fibrinolysis system?
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-Release of Tissue plasminogen activator (t-PA) (fibrinolysis) from endothelial cells
-Thrombomodulin (blocks coagulation cascade) |
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What are the steps in clot formation?
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-Primary haemostasis (platelet plug)
-Secondary haemostasis (coagulation cascade activation to stabilise clot)\ -Fibrinolysis system to remodel plug |
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What are platelets?
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Small non nucleated megakaryocyte fragments
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What is the normal level of platelets and what is the level at which increased bleeding is a risk?
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Normal; 150-450x10^9/L
Increased risk when approx 50x10^9/L |
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What is the half life of platelets?
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~4days
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What is the shape of platelets when at rest?
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Smooth non sticky discs
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What changes occur to platelets when stimulated?
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-Become spikey spheres that stick to injured surfaces and each other
-Release stored or new chemical messengers (Stored; ADP, Synthesised; thromboxane A2) -Express surface glycoproteins (GPIb, GPIIb/IIIa) |
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What are the 3 aspects of the ultrastructure of platelets outlined in the lecture?
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-Alpha granules
-Dense granules -Lysosomes |
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What is contained in the alpha granules of platelets?
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-Heparin antagonist (PF4)
-Platelet derived growth factor -Fibrinogen -von Willebrands factor -beta thromboglobulin |
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What is contained in the dense granules of platelets?
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-ADP
-ATP -5-HT -Calcium |
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What is contained in the lysosomes of enzymes?
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-hydrolytic enzymes
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What are the steps involved in platelet adhesion and aggregation?
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1.Adhesion mediated by von willebrand factor
2.Secretion of granule contents (ADP, TxA2, calcium) and surface expression of phosphoproteins (GpIIb-IIIa) 3.Platelet aggregation; ADP enables GpIIb-IIIa to bind fibrinogen 4.Deposition of fibrin |
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What is the role of vWF?
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vWF bind to exposed collagen fibres in vascular injury and GpIb receptors on platelets to form the platelet plug
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What role does ADP play in platelet aggregation?
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ADP induces a conformational change that GpIIb-IIIa to bind fibrinogen
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What is prostacyclin?
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Synthesised from arachidonic acid in endothelial cells to inhibit platelet aggregation
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What is thromboxane A2?
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Sythesised from arachiodonic acid in platelets to promote platelet aggregation
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What is the purpose of the belance between prostacyclin and thromboxane A2?
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It is mediated by [cAMP] which control [calcium] in the platelet.
High cAMP leads to low free calcium preventing aggregation and adhesion and visa versa (as calcium is involved in the coagulation cascade) |
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What is the coagulation cascade and in general terms what does it involve?
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-Intiated by exposed or new tissue factor
-Involves a series of enzymatic conversions; inactive proenzymes to activated enzymes -The enzyme reactions are accelerated by cofactors eg phospholipid surfaces -Culminates in formation of thrombin which converts fibrinogen to insoluble fibrin (clot) |
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When is the intrinsic coagulation cascade activated?
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In the presence of exposed collagen
Primary complex on exposed collagen by high molecular weight kininogen, prekallikrein and hageman factor (XIII) |
