Primary Hemostasis Flashcards
Hemostasis
-the stoppage of bleeding
-Balance between
>form clots when needed; prevent clot formation when not needed
What affects hemostasis?
-depends on integrity of blood vessels, platelet numbers and function and status/balance of coagulation factors and their inhibitors
Coagulopathy
-a disruption in the ability to form a clot
Hemostatic disorder
-a disruption that leads to insufficient clot formation OR excessive clot formation
>can be related to hemorrhage
Virchow’s Triad
**all contribute to thrombosis (predisposition for clots which clog body)
-Hypercoagulable state- hyperactive platelets and procoagulation enzymes
-Abnormal Blood flow- hyperviscosity, narrowing of vessels
-Endothelial damage
Timing of primary and secondary hemostasis
-occur at the same time, but both have a different story
Phases of primary hemostasis
**looking at platelet numbers and platelet function
-Vascular phase
-Platelet phase
Vascular phase of primary hemostasis
-Reflex vasoconstriction immediately which results in slower blood flow allowing the platelets time and exposure to subendothelial collagen under the damaged endothelial cells
>also contributes with platelets being pushed up against the walls, increasing their chances of contacting damaged wall
-Tissue factor is released by the subendothelial adventitial cells which stimulates secondary hemostasis
Platelet phase of primary hemostasis
-Platelets congregate around exposed collagen
>adhesion, aggregation and shape change from discoid to spherical
>P-selectin will enhance platelet rolling along endothelial cells adjacent to damaged focus
-clot retraction can also occur and helps reduce size of area that needs to be repaired
GpIb
-used for platelet anchoring to underlying collagen via the vWF
vWF
-von Willebrand factor
-released by damaged endothelial cells
-mediates binding of collagen to GpIb
GpIb and vWF main purpose
-binding platelets to collagen
GpIIbIIIa
-Binds fibrinogen and enhances platelet-platelet cohesion
>platelets will grab fibrinogen and different platelets will fight over it. These results in better binding between the platelets
P-selectin
-not exclusive to platelets
-enhances platelet rolling along endothelial cells adjacent to damaged focus
Platelet adhesion within primary hemostasis (platelet phase)
-takes seconds
-platelets have smaller number of surface glycoprotein called GpIb. The GpIb will bind to the vWF and only the vWF that is trapped within the extracellular collagen will bind it, which leads to the anchoring of platelet to exposed collagen
Platelet activation
-When platelets bind to collagen and substances such as thrombin, it leads to the calcium release within the cell which triggers cell changes
-An activated platelet will have a major shape change, increased GpIb presence on surface, and increased expression of GpIIbIIIa on surface to bind fibrinogen
Phospholipase activation
-occurs during platelet activation
-leads to Thromboxane A2 which further promotes aggregation and vasoconstriction
Platelet secretion
-platelets degranulate, releasing contents of alpha granules (promoting coagulation) and dense granules (promote aggregation of platelets and coagulation; contain Ca2+)
Platelet plug
-provide initial physical plug to stop hemorrhage, but also help retract the clot and make the repair area smaller
-important for secondary hemostasis
Platelet activation charge change
-When platelets activated, they change shape from discoid to spherical, but also the negatively charged phosphatidylserine moves from inside the cell membrane to the outside where it is exposed. Negative change will bind Ca which is important for secondary hemostasis
Inhibit procoagulation
-the upstream and downstream healthy endothelial cells will increase substance production when they sense damaged endothelium nearby. This is a way to prevent coagulation at the healthy sites.
>produce PGI2 which inhibits platelet aggregation
Platelet aggregation
-takes minutes (aspirin prevents the thromboxane production and therefore aggregation)
-requires fibrinogen and Ca
-increased expression of GpIIbIIIa on platelet surface promotes platelet binding between platelets as receptors bind circulating fibrinogen
Von Willebrand disease
-not producing vWF or in type 2 they produce it but it is not properly functioning; means they won’t stick to collagen and then platelets cannot grab the collagen/vWF complex for clotting
Clinical manifestations of von Willebrand disease
-Petechiation
-Purpura
vWF ELISA test
-testing for how much vWF present in patient
-70-120% is normal
-40-70% questionable
-Less than 40%- likely have Type I
Type II vWD detection
-must use multimeric analysis to determine whether multimers are present
Type III vWD
-very rare, typically patients die in utero
Thrombocytopenia
-defect in platelet function, but hemorrhage may not occur depending on platelet count
-detect by CBC or smear evaluation
-mainly acquired but can be inherited
-normal in Cavalier King Charles Spaniel
Acquired thrombocytopenia?
Mainly acquired
>increased utilization (ex. DIC, vasculitis, etc.)
>reduced production (ex.marrow disease)
>Destruction (ex. immune mediated thrombocytopenia)
>Sequestration (typically mild)
>Secondary to hemorrhage (typically mild)
Inherited thrombocytopathia
1.vWD- platelets GpIb cannot attach to collagen
2.Bernard-Soulier syndrome (GpIb deficiency) – no GpIb to attach to VWF, so platelets can’t stick/clot
Thrombopathia
-normal platelet count, through platelet function or platelet-associated factors are abnormal
