Pbt Pharmacology Of Hemostasis And Thrombosis

Front 1

what is the lifespan of a platelet?

Back 1

less than a week

Front 2

what is the importance of the fact that platelets do not synthesize proteins?

Back 2

irreversible pharmacological inhibition of platelet enzymes cannot be compensated for (EX. Aspirine and Cyclo-oxygenase)

Front 3

what 2 things do platelets bind to during activation?

Back 3

1. von Willebrand factor
2. fibrinogen

Front 4

which cell types can pass through a fibrin clot organized by platelets?

Back 4

Trick Questions cause all blood cell types will be caught in a clot

Front 5

describe the 4 stages of clot formation, localization, and size limitation?

Back 5

1. localized vasoconstriction
2. primary hemostasis = platelets activated and stick to site of injury
3. secondary hemostasis = coagulation cascade activated, fibrin cables assemble
4. anti-clotting mechanisms = natural anti-coagulant and thrombolytic factors limit size

Front 6

what do injured vascular endothelial cells release when damaged? (2)

Back 6

1. Endothelin
2. Neuro-humoral factors

Both cause vasoconstriction

Front 7

what are the 3 stages of platelet transformation beofre coagulation cascade?

Back 7

1. Platelet adhesion: i.e. initial platelet adhesion to wall and each other
2. Platelet granule release reaction: i.e. discharge of granule contents
3. Platelet aggregation and adhesion: i.e. accelerated secondary recruitment and aggregation of a local “swarm” of secondarily activated platelets under positive feedback.

Front 8

what are the 5 platelet receptors involved in platelet transformation?

Back 8

signal transducing...
1. ADP receptor
2. Thromboxane receptor

mechanical...
3. Fibrinogen receptor
4. Von Willebrand factor receptor
5. Fibrinogen receptor

Front 9

what are the two most important granule components released upon degranulation of activated platelets?

Back 9

1. ADP
2. Thromboxane

Both lead to secondary activation of other platelets via respective receptors

Front 10

what allows clots to resist collapse do to pressure of vascular flow?

Back 10

activated platelets form actomyosin filaments which have great tensil strength

Front 11

what mediates the bidning of platelets to glycoproteins on the vascular endothelial cells and sub-endothelial collagen?

Back 11

von Willebrand factor

Front 12

how does fibrin help form a clot?

Back 12

it crosslinks platelets to each other via glycorproteins on the platelet membranes

Front 13

what is a critical component to platelet activation that is found on activated endothelium?

Back 13

tissue factor

Front 14

where is prothrombin converted to thrombin?

Back 14

on platelet cell membranes

Front 15

active TxA2 receptors trigger a signaling cascade leading to?

Back 15

activation of GP-IIb-IIIa, the fibrinogen receptor with transmembrane anchor function

Front 16

what does the ADP post-receptor cascade result in?

Back 16

decreasing cAMP, which promotes clotting

Front 17

what are the two mechanisms by which drugs can stop clot formation by platelets?

Back 17

1. activation of mechano-receptors in platelet to active receptors on cell surface
2. compete with the active binding site for fibrinogen

Front 18

what are the 4 possible drug actions which can block clot formation?

Back 18

1. cyclo-oxygenase inhibitors
2. phosphodiesterase inhibitors
3. ADP receptor pathway inhibitors
4. GP-IIB-IIIA receptor antagonists

Front 19

whats an example of a cyclo oxygenase inhibitor?

Back 19

Aspirin or other NSAIDs

Front 20

whats an example of phosphodiesterase inhibitors?

Back 20

dipyridamole

Front 21

whats an example of a ADP receptor pathway inhibitor? (2)

Back 21

1. clopidogrel
2. ticlopidine

Front 22

what are 3 examples of GP-IIB-IIIA receptor antagonists?

Back 22

1. Eptifibatide
2. Abceiximab
3. Tirofiban

Front 23

what causes prothrombin to be converted to thrombin?

Back 23

combination of tissue factor on endothelial cells and acidic phosphlipids on platelets

Front 24

what is the role of thrombin?

Back 24

to form fibrin from fibrinogen

Front 25

what is the end result of fibrin formation?

Back 25

secondary hemostatic plug with fibrin mesh

Front 26

what two components are activated by thrombin IIa that lead to formation of crosslinked fibrin polymer?

Back 26

1. fibrinogen -> fibrin
2. XIII -> XIIIa which then allows for crosslinking of fibrin polymers

Front 27

what cleaves prothrombin into thrombin?

Back 27

factor Xa which is the meeting point of the common and extrinsic clotting pathways

Front 28

what effect does thrombin have on resting endothelial cells near the site of injury?

Back 28

causes them to release antithrombotic agents such as PGI2, NO, t-PA which limit clot formation

Front 29

what are the 4 natural anticoagulant and thrombolytic factors that limit homeostatic processes in vascular injury?

Back 29

1. Tissue plasminogen which activates the fibrinolytic system
2. Thrombomodulin, which activates inhibitors of the coagulation cascade
3. Prostacyclin, which inhibits both platelet activation and vasoconstriction
4. Surface heparin-like molecules which catalyze the inactivation of the coagulation factors, interactive with ATIII

Front 30

what is the difference between pro-coagulation and anti-coagulation factors as far as location relative to the clot?

Back 30

1. pro-coagulative factors are on the vessel wall by the site of the injury and other localized cells nearby
2. anti-coagulative factors are soluble and secreted so as to keep a passage way through the vessel patent as the clot forms

Front 31

what is the role of prostacyclin (PGI2)?

Back 31

increase platelet cAMP thus inhibits aggregation and granule release

Front 32

what is the role of Anti-thrombin III (ATIII)?

Back 32

Inactivates thrombin and other coagulation factors, interactive with “heparin-like” molecules

Front 33

what is the role of Protein C and Protein S?

Back 33

Vitamin K-dependent proteins slowing cascade by inactivating Va and VIIa

Front 34

what is the role of Tissue factor pathway inhibitor (TFPI)?

Back 34

Limits action of tissue factor

Front 35

what is the role of plasmin?

Back 35

Protease cleaves polymerized fibrin into fragments, after activation by tissue plasminogen activator (t PA)

Front 36

what neutralizes free plasmin?

Back 36

alpha-2 anti-plasmin

Front 37

how does heparin work?

Back 37

activates anti-thrombin III to limit clotting