Lecture 5 1/24/24 Flashcards
What is the definition of hemostasis?
interruption of blood flow through an injured vessel
What are the goals of hemostasis?
-form clot quickly
-confine clot to where needed
-limit propagation
-dissolve clot when no longer needed
What are the three main processes of hemostasis?
-formation of platelet plug (primary)
-formation of fibrin through coagulation cascade (secondary)
-formation of plasmin for clot breakdown (fibrinolysis)
How do the processes of hemostasis occur, in relation to each other?
-primary and secondary hemostasis occur about the same time
-fibrinolysis occurs in quick succession to primary and secondary hemostasis
What are the antithrombotic properties associated with “at rest” blood vessels?
-blood flow
-bioactive molecules
How do bioactive molecules prevent thrombus formation?
-vasodilation
-inhibition of platelet function/aggregation
-inhibition of coagulation
-fibrinolysis
What are the prothrombotic properties associated with “activated” blood vessels?
-exposure of subendothelial cells/activation of coagulation cascade
-turbulent blood flow
-bioactive molecules
What is tissue factor?
protein found in the collagenous extracellular matrix that is the beginning of secondary hemostasis/coagulation
How do bioactive molecules promote thrombus formation?
-vasoconstriction
-inhibition of fibrinolysis
How do platelets morphologically differ when at rest compared to activated?
-discoid/plate-shaped at rest
-spherical with multiple projections when activated
What are the components of platelet structure?
-cytoskeleton
-open canalicular system to increase surface area
-dense tubular system of ER
What are the alpha granules associated with the platelets?
-vWF
-fibrinogen
-factors 5, 7, 8, 11, 13
-PAI
What are the dense granules associated with the platelets?
-serotonin
-ADP
-Ca++
What is the role of the platelets’ alpha and dense granules?
pro-coagulation
What is the function of GpVI and Alpha2Beta1 proteins on the platelet surface?
-binds to collagen
-part of primary hemostasis
-backup plan if vWF is absent/not functioning
What is the function of Gp1b?
-vWF receptor
-part of primary hemostasis
What is the role of GpIIb-IIIa?
-fibrinogen receptor
-involved in primary and secondary hemostasis
How do Gp1b and GpIIb-IIIa differ structurally?
-Gp1b is always active and ready to bind
-GpIIb-IIIa is not active when platelet is at rest
What is the goal of primary hemostasis?
formation of the primary platelet plug
Which “players” are involved in primary hemostasis?
-platelets
-Von Willebrand factor (vWF)
-vessel wall
What are the three phases of primary hemostasis?
-platelet adhesion
-platelet activation
-platelet aggregation
What are the characteristics of vWF?
-synthesized by endothelial cells
-circulates in blood in zymogen form
-undergoes a conformational change after binding to collagen that allows for interaction with Gp1b
What is important about the Gp1b-vWF bond?
it provides stabilization against sheer forces and is difficult to disrupt
What occurs during the platelet activation stage, once the platelets are attached to collagen?
-shape change
-granule secretion
-conformational changes in surface proteins (GpIIb-IIIa)