hemostasis

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Author:
sgustafson
ID:
62855
Filename:
hemostasis
Updated:
2011-01-29 22:15:00
Tags:
hemostasis
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Description:
primary and secondary hemostasis
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  1. events following vascular injury
    • vasoconstriction (mediated by endothelin)
    • primary hemostasis - platelet activation and aggregation
    • secondary hemostasis - fibrin polymerization
    • thrombus and antithrombotic events
  2. 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
  3. 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
  4. 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
  5. 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
  6. 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
  7. D-dimers
    • formed when plasmin breaks down fibrin
    • fibrin split products
    • used to diagnose DIC, DVT, PE
  8. 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
  9. Virchow's triad
    • primary abnormalities that lead to thrombus formation
    • endothelial injury
    • stasis/turbulent blood flow
    • hypercoagulability of blood

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