Hemostasis

Question 1

efficient platelet adhesion to ECM requires what factors?

Answer 1

1. vWF (subendothelial ECM)

2. GpIb (platelet)

Question 2

what links the platelet to the endothelium?

Answer 2

vWF

Question 3

besides platelets, what else does vWF bind? what is the purpose?

Answer 3

1. factor VIII (coagulation factor)

2. prolongs half life, localizes it

Question 4

where is integrin a2b1 found? what does it do?

Answer 4

1. platelet

2. helps adherence to ECM

Question 5

what causes the dramatic shape change of activated platelets?

Answer 5

Ca2+ signal

Question 6

what is the role of TXA2 in the blood?

Answer 6

1. vasoconstriction

2. platelet activation signals

Question 7

how is TXA2 made?

Answer 7

1. arachadonic acid release upon platelet activation
2. arachadonic acid + COX = PG2
3. PG2 gives rise to TXA2

Question 8

what are the roles of ADP in the blood?

Answer 8

1. platelet activation
2. triggers change in GpIIb - GpIIIa receptor on platelets - allows receptor to bind fibrinogen for initial plug formation

Question 9

what is the most common bleeding disorder?

Answer 9

vWF disease

Question 10

how is vWF disease managed?

Answer 10

desmopressin - releases vWF from storage sites in endothelium

Question 11

what characterizes bernard-soulier syndrome? pathogenesis?

Answer 11

1. platelets fail to aggregate in response to stimuli

2. defect in interaction between vWF adn GpIb

Question 12

what characterizes glanzmann thrombasthenia? pathogenesis?

Answer 12

1. platelets fail to aggregate in response to various stimuli
2. defect in GpIIb and / or GpIIIa

Question 13

the coagulation cascade ultimately leads to activation of what compound?

Answer 13

thrombin

Question 14

the intrinsic and extrinsic pathways converge on the activation of what factor?

Answer 14

factor X (results in activation of thrombin)

Question 15

what is the key regulator of coagulation?

Answer 15

factor X

Question 16

partial thromboplastin time test tests which arm of the coagulation cascade?

Answer 16

intrinsic

Question 17

prothrombin time test tests which arm of the coagulation cascade?

Answer 17

extrinsic

Question 18

where is factor VIII produced?

Answer 18

endothelium

Question 19

prothrombin and factors VII, IX, and X contain which modified amino acid residue?

Answer 19

carboxyglutamate

Question 20

what is the role of caroboxyglutamate?

Answer 20

1. chelates Ca2+
2. bound Ca2+ binds negatively charged membrane lipids
3. clotting factors are active when bound to cell membranes
4. restricts clot formation to site of injury

Question 21

what is responsible for restricting clot formation to the site of injury?

Answer 21

carboxyglutamate

Question 22

what is required for carboxylase to to convert glutamate to carboxyglutamate?

Answer 22

vitamin K

Question 23

warfarin inhibits what enzyme? what is the result?

Answer 23

1. vitamin k epoxide reductase

2. prevents regeneration of vitamin k

Question 24

what forms the extrinsic Xase complex?

Answer 24

X + VII + III

Question 25

what is the role of the Xase complex?

Answer 25

activation of X

Question 26

what is the role of factor Xa?

Answer 26

slow cleavage of prothrombin to make thrombin

Question 27

which factors does thrombin activate?

Answer 27

V, fibrinogen, VII, VIII to sustain and accelerate extrinsic pathway

Question 28

what makes up the prothrombinase complex?

Answer 28

X + Va

Question 29

what is the role of the prothrombinase complex?

Answer 29

RAPID cleavage of prothrombin to make thrombin

Question 30

what does the intrinsic Xase complex do?

Answer 30

rapid activation of thrombin

Question 31

what is the role of transglutaminase?

Answer 31

forms bonds between lysine and glutamine in fibrin monomers - generates hard cross linked clot

Question 32

hemophilia A is a deficiency in what factor?

Answer 32

VIII

Question 33

hemophilia B is a deficiency in what factor?

Answer 33

IX

Question 34

what are the endogenous anticoagulant activities?

Answer 34

1. thrombin 2. protein C and S 3. serpins 4. TFPI

Question 35

what does thrombomodulin do?

Answer 35

1. alters thrombin 2. thrombin/thrombomodulin activates protein C 3. C binds S 4. C/S degrades Va and VIIIa - blocks clotting

Question 36

what is the significance of factor V Leiden?

Answer 36

resistant to cleavage by protein C - hypercoagulation

Question 37

what do the serpins do?

Answer 37

1. inhibit activated forms of coagulation factors | 2. binds antithrombin III and heparin

Question 38

what does TFPI do?

Answer 38

1. inhibits VIIa - blocks extrinsic | 2. inhibits Xa

Question 39

what degrades fibrin?

Answer 39

plasmin

Question 40

what stimulates TPA release?

Answer 40

protein C

Question 41

what does streptokinase do?

Answer 41

activator of plasminogen - breaks up clots