Hemostasis Flashcards

1
Q

efficient platelet adhesion to ECM requires what factors?

A
  1. vWF (subendothelial ECM)

2. GpIb (platelet)

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2
Q

what links the platelet to the endothelium?

A

vWF

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3
Q

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

A
  1. factor VIII (coagulation factor)

2. prolongs half life, localizes it

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4
Q

where is integrin a2b1 found? what does it do?

A
  1. platelet

2. helps adherence to ECM

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5
Q

what causes the dramatic shape change of activated platelets?

A

Ca2+ signal

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6
Q

what is the role of TXA2 in the blood?

A
  1. vasoconstriction

2. platelet activation signals

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7
Q

how is TXA2 made?

A
  1. arachadonic acid release upon platelet activation
  2. arachadonic acid + COX = PG2
  3. PG2 gives rise to TXA2
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8
Q

what are the roles of ADP in the blood?

A
  1. platelet activation
  2. triggers change in GpIIb - GpIIIa receptor on platelets - allows receptor to bind fibrinogen for initial plug formation
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9
Q

what is the most common bleeding disorder?

A

vWF disease

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10
Q

how is vWF disease managed?

A

desmopressin - releases vWF from storage sites in endothelium

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11
Q

what characterizes bernard-soulier syndrome? pathogenesis?

A
  1. platelets fail to aggregate in response to stimuli

2. defect in interaction between vWF adn GpIb

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12
Q

what characterizes glanzmann thrombasthenia? pathogenesis?

A
  1. platelets fail to aggregate in response to various stimuli
  2. defect in GpIIb and / or GpIIIa
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13
Q

the coagulation cascade ultimately leads to activation of what compound?

A

thrombin

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14
Q

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

A

factor X (results in activation of thrombin)

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15
Q

what is the key regulator of coagulation?

A

factor X

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16
Q

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

A

intrinsic

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17
Q

prothrombin time test tests which arm of the coagulation cascade?

A

extrinsic

18
Q

where is factor VIII produced?

A

endothelium

19
Q

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

A

carboxyglutamate

20
Q

what is the role of caroboxyglutamate?

A
  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
21
Q

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

A

carboxyglutamate

22
Q

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

A

vitamin K

23
Q

warfarin inhibits what enzyme? what is the result?

A
  1. vitamin k epoxide reductase

2. prevents regeneration of vitamin k

24
Q

what forms the extrinsic Xase complex?

A

X + VII + III

25
Q

what is the role of the Xase complex?

A

activation of X

26
Q

what is the role of factor Xa?

A

slow cleavage of prothrombin to make thrombin

27
Q

which factors does thrombin activate?

A

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

28
Q

what makes up the prothrombinase complex?

A

X + Va

29
Q

what is the role of the prothrombinase complex?

A

RAPID cleavage of prothrombin to make thrombin

30
Q

what does the intrinsic Xase complex do?

A

rapid activation of thrombin

31
Q

what is the role of transglutaminase?

A

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

32
Q

hemophilia A is a deficiency in what factor?

A

VIII

33
Q

hemophilia B is a deficiency in what factor?

A

IX

34
Q

what are the endogenous anticoagulant activities?

A
  1. thrombin
  2. protein C and S
  3. serpins
  4. TFPI
35
Q

what does thrombomodulin do?

A
  1. alters thrombin
  2. thrombin/thrombomodulin activates protein C
  3. C binds S
  4. C/S degrades Va and VIIIa - blocks clotting
36
Q

what is the significance of factor V Leiden?

A

resistant to cleavage by protein C - hypercoagulation

37
Q

what do the serpins do?

A
  1. inhibit activated forms of coagulation factors

2. binds antithrombin III and heparin

38
Q

what does TFPI do?

A
  1. inhibits VIIa - blocks extrinsic

2. inhibits Xa

39
Q

what degrades fibrin?

A

plasmin

40
Q

what stimulates TPA release?

A

protein C

41
Q

what does streptokinase do?

A

activator of plasminogen - breaks up clots