Exam 4 - Weber Hockerman Campbell Thurman Flashcards
platelets derive from __________
megakaryotes
platelets have no _________
nucleus or genes
what are the three steps of platelet formation?
adhesion, secretion, aggregation
platelets: adhesion is mediated by:
- GP Ia binding to collagen
- GP Ib binding to vWF bridged to collagen
- shape changes facilitates receptor binding
- intact endothelial cells secrete PGI2 (prostacyclin) to inhibit thrombogenesis)
platelets: secretion release reaction
- degranulation
- platelet granules release ADP, 5-HT, TXA2
- these molecules activate and recruit other platelets
- TXA2 and 5HT are potent vasoconstrictors
what molecules are released from platelet granules
ADP, TXA2, 5-HT
which molecules released from platelets are potent vasoconstrictors
TXA and 5-HT
platelet aggregation steps
- ADP, 5-HT, TXA2 activation induces conformation of GPIIb/IIIa receptors to bind fibrinogen
- platelets are crossed-linked by fibrogen
- forms temporary hemostatic plug
- platelets contract to form irreversible fused mass
- fibrin stabilizes and anchors aggregated platelets
- forms surface for clot formation
what does GPIIb/IIIa bind to?
fibrinogen
platelets are _______ by fibrinogen
cross-linked
COX-1 inhibitors MOA
irreversible inhibition of TXA2 synthesis in platelets
aspirin use leads to a _______ loss of platelet COX1 activity
permanent
indications of aspirin
prophylaxis and treatment of arterial thromboembolic disorders
- prevents coronary thrombosis in unstable angina
- adjunct to thrombolytic therapy
- reducing recurrence of thrombotic stroke
clinical actions of aspirin
- prolongs bleeding time but no increase in PT time
- hemostasis returns to normal 36 hours after last dose
side effects of aspirin
- upper GI bleeding
- aspirin overdose
why do selective COX inhibitors cause increased CV risk
selective COX2 inhibitors block synthesis of prostacyclin while not preventing the synthesis of TXA2 (increased risk of clotting)
ADP RIs: P2Y1s couple to which pathway
Gq - PLC - IP3 - Ca2+ - pathway
ADP RIs: P2Y12s couple to which pathway
G1 and inhibition of adenylyl cyclase
activation of both P2Y1 and P2Y12 receptors is not required for platelet activation by ADP
false
Name the P2Y12 ADP Receptor inhibitor
clopidogrel (plavix)
MOA of clopidogrel (plavix)
irreversibly block ADP receptor on plateelt and subsequent activation of GP IIb/IIIa
duration of action of clopidogrel after d/c
several days after last dose