hemostasis pharm

Question 1

3 steps of formation of a clot

Answer 1

1. vessel constriction
2. platelet adhesion, activation, aggregation (platelet plug)
3. cross-linking of fibrin thru coagulation cascade

Question 2

upon injury, vascular endothelial cells begin to produce ____ and _____, potent vasoconstrictors acting on smooth muscle; this helps to limit hemorrhage

Answer 2

prostaglandin F2a and thromboxane A2

Question 3

the ECM is exposed at the injury site; this allows platelets to bind to matrix proteins ____, ____ and ____; this binding leads to platelet activation

Answer 3

collagen, fibronectin, von willebrand factor

Question 4

products secreted by activated platelets include:

Answer 4

thromboxane A2 (vasoconstriction), PG F2a (vasoconstriction), ADP (platelet aggregation), and serotonin (vasoconstriction and platelet aggregation)

Question 5

platelet activation leads to a conformation change in ____ that allows it to bind ____, a plasma protein; the platelets aggregate as a result of ____; this is the platelet plug

Answer 5

an integrin receptor; fibrinogen; fibrinogen cross-linking

Question 6

proteolytic cleavage of fibrinogen, by ____, to form fibrin, followed by chemical cross-linking by _____ produces a blood clot

Answer 6

thrombin; factor XIII

Question 7

as platelet activation and aggregation is taking place, _____ are initiated; ____ is most important

Answer 7

extrinsic and intrinsic coagulation pathways; extrinsic pathway

Question 8

in order for the extrinsic pathway to start, ____ (a serine protease that needs to be activated by proteolytic cleavage) must be complexed with ____

Answer 8

Factor VII; tissue factor (TF)

Question 9

TF is present in the ____ (ECM of endothelial cells, subendothelium); it is not exposed to the blood unless _____

Answer 9

basement membrane; the tissue is damaged

Question 10

complex of TF-VIIa can activate ____, but primary procoagulent effect is via activation of ____ to ____

Answer 10

X; factor IX to IXa

Question 11

mainly IXa and some Xa make their way to activated platelets and form _____ that include Ca and membrane phospholipids; these complexes also include factors ____ and ____

Answer 11

chelate complexes; VIIIa, Va

Question 12

IXa-VIIIa complexes activate X to Xa, allowing for the formation of _____

Answer 12

Xa-Va complexes

Question 13

the Xa-Va complex will cleave ____ to ____, producing the enzyme that will create a blood clot

Answer 13

prothrombin (II); thrombin (IIa)

Question 14

cleavage of ____ by thrombin (IIa) exposes binding sites, resulting in the formation of a ____

Answer 14

fibrinogen; fibrin mesh

Question 15

thrombin will also cleave and activate the clotting factors:

Answer 15

V, VIII, and XI

Question 16

intrinsic pathway also contributes to blood clotting; factor ___ is activated by contact with ____

Answer 16

XII; polyanions

Question 17

activated platelets secrete inorganic polymers, _____; contact with these activates ____ and the intrinsic pathway is initiated

Answer 17

polyphosphates; factor XII

Question 18

thrombin also activates ____, an enzyme that cross-links the fibrin mesh

Answer 18

factor XIII

Question 19

all the things thrombin activates:

Answer 19

fibrin (via fibrinogen), factors V, VIII, XI and XIII

Question 20

a small protein molecule that is a serine protease inhibitor that inactivates several enzymes of the coagulation system

Answer 20

antithrombin (AT)

Question 21

AT is produced by the ____; it’s activity is increased many fold by anticoagulent drug ____, which enhances the binding of AT to _____ and _____

Answer 21

liver; heparin; factor II (thrombin) ; factor X

Question 22

clotting factors inhibited by AT:

Answer 22

XII, X, IX, VII, II (thrombin)

Question 23

a zymogen, the activated form of which plays an important role in regulating coagulation

Answer 23

protein C (autoprothrombin IIA or blood coagulation factorXIV)

Question 24

activated protein C (APC) proteolytically inactivates ____ and ____; APC is classified as a _____

Answer 24

factors Va and VIIIa; serine protease

Question 25

the protein C zymogen is activated when it binds to _____; protein C’s activation is greatly promoted by the presence of _____ and _____

Answer 25

thrombin; thrombomodulin; endothelial protein C receptors (EPCRs)

Question 26

single chain polypeptide which can reversibly inhibit factor Xa

Answer 26

tissue factor pathway inhibitor (TFPI)