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events following vascular injury
- vasoconstriction (mediated by endothelin)
- primary hemostasis - platelet activation and aggregation
- secondary hemostasis - fibrin polymerization
- thrombus and antithrombotic events
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primary hemostasis
- platelets attach to endothelium exposed collagen by a von Wildebrand Factor bridge to GpIb
- vWF-GpIb necessary to overcome shearing forces
- Secretion of alpha-granules (fibrinogen, fibronectin, factors V, VIII, platelet-derived growth factor (PGDF), transforming growth factor-beta (TGF-beta)) and dense granules (ADP, ATP, Ca2+, histamine, serotonin, EPI)
- Platelet activation -> exposed phosphatidylserine& neg charged PLs
- thromboxane A2 stimulates aggregation
- fibrinogen acts as bridges between platelet GpIIb-IIIa receptors
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secondary hemostasis
- extrinsic - needs tissue factor, PT (prothrombin time)
- intrinsic - needs only neg charged surface, PTT (partial thromboplastin time)
- converge at activation of factor X
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extrinsic pathway
- warfarin-sensitive
- tissue factor, PT - prothrombin time
- VII activates tissue factor to VIIa
- VIIa can activate X and IX (part of intrinsic pathway)
- PT: VII, X, II, V, fibrinogen
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intrinsic pathway
- PTT: XII, XI, IX, VIII, X, V, II, fibrinogen
- only requires neg. charged particles
- XII->XIIa by collagen
- XIIa can convert prekalikrein, XI->XIa
- XI can also be activated by thrombin (IIa)
- XIa converts IX->IXa
- thrombin converts VIII->VIIIa
- VIIIa+IXa+Ca2+ activate X
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3 categories of endogenous anticoagulants
- antithrombins (antithrombin III): endogenous heparin, inhibit intrinsic cascade + thrombin
- Protein S and C: vit K-dependent, activated by thrombomodulin, inactivates Va, VIIIa
- TFPI: inactivates tissue factor-VIIa complexes
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D-dimers
- formed when plasmin breaks down fibrin
- fibrin split products
- used to diagnose DIC, DVT, PE
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t-PA
- plasminogen activator
- plasmin then cleaves fibrin
- tPA's action is confined to sites of recently-formed clots
- opposed/balanced by PAI - plasminogen activator inhibitor
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Virchow's triad
- primary abnormalities that lead to thrombus formation
- endothelial injury
- stasis/turbulent blood flow
- hypercoagulability of blood
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