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23 Cards in this Set

  • Front
  • Back
What is the definition of a thrombus?
Platelet plug and Fibrin Clot
What 3 things occur in response to vascular injury?How long is each?
Vasoconstriction
Primary hemostasis-plug formation, few secs
Secondary hemostasis-fibrin clot, few minutes
What are the 3 types of granules in platelets? Contents?
Dense granules- Ca and ADP
alpha granules- vwF, Fibrinogen, Factor V, serotonin, PDGF
Dense tubular system-like ER, filled with Ca++
How are platelets regulated and kept in the quiscent state?
Endothelial cell secrete PGI2(vasodilation, plug inhibition)
which binds Gs and increases camp. cAMP causes dense tubular systems to remove Ca=low IC calcium so remains inactive
What are the 5 stages of primary hemostasis?
Adhesion
Activation
Secretion\degranulation
Shape change
Aggrigation
How can platelets be activated?
autocrine TXA2 or Thrombin or several other agonists like epinephrine that initiate a Gq cascade
What occurs with plug formation agonist with respect to signalling cascade?
Gq activation>>IP3 and DAG>>increased Calcium>>PLA cleavage>>AA>>TXA2 formation
What initiated the degranulation phase?
Formation of TXA2 during activation causes secretion of all platelets granules
How does degrenulation aid furthur platelet aggrigation? What drug inhibits this?
ADP in dense granules stimulates aggrigation. Plavix is a ADP receptor antagonist
How does degranulation aid shape change?
Secretion adds 60% more phospholipids, increasing surface area leading to more flexibility
What causes shape change?
the increase in calcium during activation activates MLC-P(myosin light chain proteins) and causes actin contraction
What changes occur to platelet during shape change?
GPIIb\IIIa is exposed on the platelets, as is phosphatidyle serine. This makes it more negative and promotes binding of factor VIII(tenase complex) and factor V(prothrombinase complex)
What occurs during aggregation phase of primary hemostasis?
GpIIb\IIIa that were flipped out can bind to fibrinogen and link platelets together
What causes shape change?
the increase in calcium during activation activates MLC-P(myosin light chain proteins) and causes actin contraction
What changes occur to platelet during shape change?
GP1B\IIIa is exposed on the platelets, as is phosphatidyle serine. This makes it more negative and promotes binding of factor VIII(tenase complex) and factor V(prothrombinase complex)
What occurs during aggregation phase of primary hemostasis?
GpIIb\IIIa that were flipped out can bind to fibrinogen and link platelets together
What part of fibrinogen binds to GPIIB\IIIa?
RGD motifs of fibrinogen
What is the clinical use of the drug integrellin?
Has and RGD motif that binds activated platelets and prevents aggrigation by acting like fibrinogen
Which COX synthesizes TXA2? Which synths PGI2?
COX1-TXA2


COX2-PGI2
Why does low does asprin therapy inhibit platelet formation?
Since platelets lack nucleus they cannot overcome the loss of COX1 to sythesize TXA but endothelial cells can so they make more COX2 and hence PGI2 and inhibit plug formation
How does adhesion occur in response to vascular injury?
Exposed collagen binds to vwF, shear forces change conformation of vwf\collagen complex so they may bid to GP1B\IX on platelets. NOTICE IX not activated
how does vwF affect factor VIII?
increases half life
Why are arterial thrombi more full of platelet plugs?
Because of the high shear forces that favor their formation