App 13 - Hemostasis Session Flashcards
overview of primary hemostasis
How do you measure platelet aggregation in blood?
What is thromboxane? Where/when is it important?
What are the components of the coagulation cascade?
Why is vitamin k important in secondary hemostasis (stabilizing the platelet plug)?
How is coagulation inhibited until endothelial cell injury?
describe the 2 pathways in coagulation generally? Where do they meet?
Traditionally, the coagulation cascade was divided into two initiating pathways, the intrinsic and extrinsic pathways, which converged (at the level of factor X) into a final common pathway.
intrinsic: contact→7a→11a→ 9a→ 9a+8+4(Ca)+phospholipid → 10a
extrinsic: Tissue factor → 7a + Phospholipid + 4(Ca) → 10a
or Tissue factor + 7a → 9a + 8 + 4(Ca) → 10a
common:
10a + 5 + PL + 4(Ca) → 2a (thrombin)
fibrinogen + 2a (thrombin) → fibrin fibrin+8a→ stable clot
2a (thrombin) + 8 → 8a
Why is the extrinsic pathway particularly important?
The modern concept of secondary hemostasis has undergone revision with the recognition that the classic extrinsic pathway is the primary initiator of coagulation (and that “contact” activation of the intrinsic pathway probably is of minimal importance in vivo). Tissue factor binds to and activates factor VII (in the presence of a phospholipid surface and calcium) and this complex is able to activate factor X. Alternatively, the tissue factor/factor VII complex can activate factor IX (of the traditional intrinsic pathway), which in turn complexes with factor VIIIa, a phospholipid surface and calcium to activate factor X.
Why is thrombin important?
The generation of thrombin is a critical step in the coagulation cascade. Thrombin catalyzes the conversion of fibrinogen to fibrin, which is the ultimate substrate of the coagulation pathway.
How is the coagulation cascafe regulated?
Tissue factor pathway inhibitor (TFPI) is lipid-bound molecule, which circulates in the blood and also can be bound to endothelial cells and platelets. TFPI binds to and inactivates the tissue factor/factor VII
complex, as well as factor Xa.
Antithrombin (III) is a molecule, which reversibly binds to and inactivates thrombin and to some extent other serine proteases. The action of antithrombin is significantly enhanced by binding to heparin.
The cofactors involved in the coagulation cascade are inactivated by
protein C. Protein C is a vitamin K-dependent protein that is activated by thrombomodulin-bound thrombin in the presence of a cofactor, protein S (which is also vitamin K-dependent).
cross-linked fibrin can be broken down by the fibrinolytic system, specifically through the action of plasmin. Endothelial cells secrete tissue plasminogen activator, which activates plasminogen
to plasmin, which is then able to degrade cross-linked fibrin into smaller fragments
how is coagulation assessed in lab?
What is the difference between the coagulation lab tests?
What is the international normalized ratio?
