Platelet Biohem And Fibrin Production And Inhibition Flashcards
Primary hemostasis
. Formation of a platelet plug
. Initiated in response to a vascular injury
Platelets
. Cell fragments derived from megakaryocytes
. Maintain vascular integrity through primary hemostasis
. Provide surface to promote coagulation cascades (secondary hemostasis)
. Produces mediators to promote healing (PDGF)
Platelet derived growth factor (PDGF)
Activates Tyr kinase to promote cell proliferation and wound healing
Why do intact endothelial cells not interact with platelets?
. Cells and platelets both have net negative surface charges and may repel each other
. Cells synthesize factors that inhibit hemostasis and platelet aggregation (prostacyclin, thrombomodulin, heparin sulfate, plasminogen activators, NO, ADPase )
Formation of primary platelet plug
. Subendothelial ECM glycoproteins are exposed (collagen, vWF)
. Platelets adhere to glycoproteins or Gp receptors
. Adherence induces signal transduction across platelet membrane leading to activation and release of coagulation mediators (ADP and TXA2)
. Activate platelets recruit other platelets and aggregate
Gp receptors
. Gp that binds to collagen in subendothelium
. Gp that binds vWF in suendothelium
. Gp II-IIIa: binds fibrinogen in blood
Gp IIb-IIIa is a member of the ____ family
Integrin
Platelet aggregation
. Activated platelets undergo conformational change in Gp IIb-IIIa allowing them to bind to fibrinogen w/ high affinity
. Binding to fibrinogen and thrombin stimulates additional platelet aggregation through platelet-platelet interaction
. Bound fibrinogen is enzymatically cleaved to fibrin through coagulation cascades (secondary hemostasis)
. Fibrin becomes entwined in and stabilizes primary hemostasis plug creating secondary plug
Thrombin
. Very potent inducer of platelet aggregation
. Product of hemostasis
. Induces further platelet aggregation and the release of agents like TXA2 and ADP
Bernard-Soulier disease
. Platelet disorder
. Defect in Gp Ib-IX
Glanzmann thrombasthenia
. Platelet disorder
. Defect in Gp IIb-IIIa
Von willebrand disease
. Deficiency/defect in VWF
. Most common bleeding disorder
. Autosomal dominant gene on chromosome 12
. Usually no treatment unless person is going into surgery
. Usually noticed first during dental procedures
Aspirin
. Irreversible inhibitor of COx in platelets
. Prevents inhibited platelet from producing TXA2
. Does not thin the blood
. Not an anticoagulant
Thromboxane A2 (TXA2)
. Very potent inducer of platelet aggregation
. Required for formation of platelet aggregates and platelet plug
Platelet receptor inhibitors
. Agents bind to glycoprotein (Gp) recents on platelets and prevent binding to normal ligand
.
T/F platelet plug is not stable
T, will not stay in place w/o reinforcement
Intrinsic coagulation pathway
. All required components in plasma
. Plasma + phospholipid of platelet -> fibrin for stable clot
Extrinsic coagulation pathway
. Requires external factor (tissue factor) for fibrin formation
. Must add something to plasma for clot to form
Extrinsic pathway of coagulation ____ the process while intrinsic pathway _____ the process
. Extrinsic initiates
. Intrinsic continues
T/F proteases in coagulation are found in plasma as zymogens
T, when active add a to the end of factor name (factor X to factor Xa when active)