endothelial cells and platelets Flashcards
endothelial cells are _____ regulators of hemostasis
central
endothelium maintains a balance between ____ and _____ activitities
anti- and pro- thrombotic activitities
T or F… anticoagulent factors are expressed under normal conditions
true
T or F… pro-coagulant activites are acquired following injury
true
fibrinolysis: t-PA cleaves?
plasminogen into plasmin which cleaves fibrin
what cleaves fibrin?
plasmin
antiplatelet
- intact endothelium prevents contact with ECM
- prostacyclin (PGI2) and nitirc oxide are vasodilators and inhibit platelet adhesion and aggreagtion
- adenosine diphophatase, which degrades ADP, inhibits platelet aggregation
anticoagulant
- heparin-like molecules: co-factors that allow antithrombin 3 to inactivate thrombin (factors9a and 10a)
- thrombomodulin: binds thrombin > cleaves and activates protein C along with protein S > inactivates factors 10a and 13a
- tissue factor pathway inhibitor (TFPI) inhibits tissue factor-factor 7a complex and factor 10a
prothrombotic properties of injured or activated endothelium
1) activation of platelets
2) von Willebrand factor (vWF)
- producued by endothelial cells
- bound to ECM
- binds to Gp1b on the surafce of platelets
tissue factor is produced in response to TNF, IL-1, bacterial endotoxin. It activates and downregulates what?
- activates coagulation
* downregulates thrombomodulin
what limits fibrinolysis?
plasminogen activator inhibiot (PAIs)
clotting factors binding tofactors _____ and ____, augment theircatalytic activities
9a anad 10a
are platelets cells?
NO! they are cellular fragments
platelets are critical in ?
hemostasis; formation of hemostatic plug, recruit and concentrate coagulation factors
two types of platelet granules?
1) alpha granules
2) dense bodies (delta granules)
alpha platelet granules express?
express P-selectin and contain fibrinogen, fibronectin, factors 10 and 13, platelet factor-4, PDGF,TGF-beta
dense plateket bodies (delta granules) contain?
contain ADP and ATP, ionized calcium, histamine, serotonin, and epinephrine
histamine and serotonin affect on blood vessels?
vasodilation
epinephrine affect on blood vessels?
vasoconstriction
4 processes of platelets?
1) platelet adhesion
2) activation
3) aggregation
4) platelet-endothelial interactions
platelet adhesion initiates? is mediated through?
- initiates clot formation
* mediated through vWF and glycoprotein Gp1b
Platelet Activation
release of alpha granules and dense bodies (delta granules)
- production of thromboxane A2
- change in shape to increase surface area to bind to vWF
1) Platelet aggreagation bridging interaction?
2) thrombin stabolizes
3) thrombin converts
4) are RBCs and WBCs present?
1) bridge in interactions between fibrinogen and Gp2b/3a receptors
2) thrombin stabilizes the platelet plug via activation of a protease-activated receptor (PAR)
3) thrombin converts fibrinogen to fibrin
4) RBCs and WBCs are also present
protease-activtated receptor (PAR) is a ______ hemostatic plug
secondary
platelet-endothelial interactions is a balance between opposing effects of
prostacyclin (PGI2) and thromboxane A2 (TxA2)
prostacyclin (PGI2) and thromboxane A2 (TxA2) which one dominates?
- prostacyclin (PGI2) = during normal vessels
* thromboxane A2 (TxA2) = during endothelial injury injury (and PGI2 decreases)
prostacyclin (PGI2) affect on blood vessels?
vasodilator, inhibits platelet aggregation
thromboxane A2 (TxA2) affect on blood vessels?
vasoconstrictor
what is the ultimate goal of clinical inhibition of platelet aggregation?
to lower the risk of coronary thrombosis
what are two common drugs used to clinically inhibition of platelet aggregation?
aspirin and plavix
what is aspirins affect on platelet aggregation?
permanently blocks platelet formation of TxA2 (also used as profilactic for heart probs)
what is plavixs affect on platelet aggregation? aka?
plavix (clopidogrel) is an ADP antagonist only
*(ADP is a platelets activator)
proteins ___ and ___ work together to activate factos 5a and 8a?
C and S
heparin-like molecules are co-factors that allowantithrombin 3 to inactivate?
thrombin, factor 9a and factor 10a
prostacyclin (PGI2) and nitric oxide have what affect on blood vessels? inhibit what aspect of platelets?
vasodilators
*inhibit adhesion and aggregation
