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Hematology > Hemostasis > Flashcards

Hemostasis Flashcards

1
Q

What is the protein that is activated by the coagulation cascade?

A

thrombin

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2
Q

What is the function of thrombin?

A

Cleaves fibrinogen into fibrin

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3
Q

What is the protein found on platelets that interacts with vWF?

A

Glycoprotein Ib

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4
Q

What is the glycoprotein on platelets that serves as the attachment point for other platelets?

A

Gp IIa/IIIb

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5
Q

What is the role of factor VIII?

A

Binds to vWF, and promotes coag

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6
Q

What is integrin Alpha2Beta1?

A

Receptor on the surface of platelets, that binds to collagen

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7
Q

What happens to platelets as they bind to vWF? What is the signal for this?

A

undergo a shape change (disc to sphere) in response to Ca

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8
Q

What are the two granules that platelets secrete?

A

Alpha

Delta (dense)

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9
Q

What are the chemicals found in delta granules? (6)

A 
ADP
ATP
Ca
Histamine
5HT
Epi
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10
Q

What are the chemical found in alpha granules?

A

Fibrinogen
Fibronectin
vWF
factor V

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11
Q

Activation of platelets causes the release of what precursor molecule for protaglandins?

A

Arachidonic acid

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12
Q

What is the enzyme that converts arachidonic acid into prostaglandin G2?

A

COX

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13
Q

What does prostaglandin g2 get turned into? What next?

A

Prostaglandin H2, then into thromboxane A2 via thromboxane synthase

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14
Q

What is the enzyme that converts prostaglandin H2 into thromboxane A2?

A

Thromboxane synthase

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15
Q

Thromboxane, 5HT, and epi serve to do what to blood vessels?

A

vasoconstriction

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16
Q

What are the two major aggregation signals for platelets?

A

ADP

Thromboxane A2

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17
Q

What is the MOA of ADP increasing aggregation of platelets?

A

conformation change of GpIIb/IIIa, allowing fibrinogen to attache

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18
Q

What is von Willebrand disease?

A

decrease in vWF protein levels, function, and a decrease in factor VIII binding

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19
Q

What is the most common bleeding disorder?

A

vWF disease

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20
Q

What are the symptoms of von Willebrand disease?

A

Excessive bleeding and easy bruising/bleeding that presents in early childhood

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21
Q

What is the treatment for von Willebrand disease? MOA?

A

Desmopressin–stimulates the release of vWF and factor VIII

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22
Q

What is Bernard-Soulier syndrome?

A

Giant platelet secretion/thrombocytopenia, and defect in the interaction of gpIb and vWF

Causes an inability of platelet to adhere correctly

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23
Q

What is the treatment for Bernard-Soulier syndrome?

A

minimize bleeding risk

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24
Q

What is Glanzmann thrombasthenia?

A

Quantitative/qualitative defects in GpIIb/IIIa

Prolonged bleeding time d/t reduction in platelet aggregation

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25
Q

Defect in GpIb/vWF = what disease?

A

Bernard-Souilier

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26
Q

Defect in GP IIa/IIIb results i what disease?

A

glanzmann thrombasthenia

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27
Q

Decreased vWF = what disease?

A

von Willebrand disease

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28
Q

What is the convergence point of the coagulation cascades?

A

factor X

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29
Q

Why is the extrinsic pathway named as such?

A

Exogenous material (tissue factor) was needed to activate it

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30
Q

Which pathway is activated upon exposure to negatively charged surfaces?

A

intrinsic pathway

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31
Q

What are zymogens?

A

inactive precursors of proteins

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32
Q

factor I = ? Where is it produced?

A

Fibrinogen, liver

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33
Q

factor II = ? Where is it produced?

A

Prothrombin

Liver

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34
Q

factor III = ? Where is it produced?

A

Tissue factor

Most everywhere

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35
Q

factor VI = ? Where is it produced?

A

Ca

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36
Q

factor V= ? Where is it produced?

A

Proaccelerin

Liver

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37
Q

factor VI = ? Where is it produced?

A

no such thing

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38
Q

factor VII = ? Where is it produced?

A

Proconvetrin

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39
Q

What are the factors that need vit k to function? What is the molecule that they all have in common that needs vit K?

A

10, 9, 7, 2

gamma carboxyglutamate

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40
Q

What is the enzyme that requires vitamin K as a cofactor?

A

Carboxylase

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41
Q

What is endothelin, and what does it do?

A

Local factor produced by endothelial cells that causes vasoconstriction

42
Q

What is the cement part of the clot?

A

Fibrin

43
Q

Do platelets have RNA?

A

Small amount

44
Q

What is the mineral that is secreted by platelets that causes activation of the coag cascade?

A

Ca

45
Q

What is the cytokine that triggers the change in conformation of GpIIb/IIIa to allow for the receptor to bind to fibrinogen?

A

ADP

46
Q

What is the basis of the partial thromboplastin time test?

A

Intrinsic pathway will clot with exposure to negative charges on glass

47
Q

What is the purpose of the gamma carboxyglutamate on factors 10, 9, 7, and 2?

A

Chelates Ca a lot better than glutamate does, allowing for Ca ions to coordinate negatively charged lipid membranes and keeping them bound

48
Q

What is the enzyme that is inhibited by warfarin? What does this do?

A

Vitamin K epoxide reductase, prevents Vitamin K from being reduced back to its usable form

49
Q

What type of molecule is factor 7? What does it do?

A

Serine protease that cleaves factor X, another serine protease

50
Q

What type of molecule is factor 10?

A

Serine protease

51
Q

factor Xa catalyzes the slow or fast cleavage of prothrombin?

A

Slow

52
Q

What type of molecule is factor X? What is its function?

A

Serine protease, that cleaves factor V

53
Q

What are the two components of the prothrombinase complex? What does this do?

A

Factors V and X

cleaves prothrombin rapidly

54
Q

What are the three major functions of thrombin?

A
  1. Cleave fibrinogen
  2. activates factor V and VII (positive feedback
  3. Activate factor VIII (intrinsic pathway)
55
Q

What is the test that is used to assess the intrinsic pathway?

A

PTT

56
Q

What is the first factor that is activated in the intrinsic pathway? How?

A

Factor XII by exposure to negatively charged surfaces

57
Q

What are the two factors that factor XII activates? What is this factor complexed with?

A

Factor XI, which is complexed with prekallikrein to form a high molecular weight kininogen (HMWK)

58
Q

What is the factor that factor XI activates?

A

factor IX

59
Q

What is the factor that factor IX activates? Is this a fast or slow reaction?

A

factor X, slow

60
Q

Thrombin cleaves what factor

A

VIII

61
Q

What are the factors that form the intrinsic tenase complex? What is the function of this complex?

A

VIII, IX.

Rapid activation of factor X

62
Q

What is the factor that must be activated to form the hard clot? What type of molecule is this?

A

XIII

transglutaminase

63
Q

What is the amino acid bond that factor XIII catalyzes in fibrin?

A

K to a E

64
Q

What is the mode of inheritance for hemophilia A and B?

A

xLR

65
Q

What is the most common hemophilia?

A

A

66
Q

What is the pathophysiology of hemophilia A?

A

deficiency of factor 8 production

67
Q

What is the pathophysiology of hemophilia B?

A

Deficiency of factor IX production

68
Q

What is the treatment for hemophilia A and B?

A

Recombinant factor (8 or 9 for A and B respectively)

69
Q

How does thrombin inhibit clotting?

A

when thrombin is bound to a membrane protein of endothelial cells referred to as thrombomodulin, the specificity of thrombin is altered. Rather than promoting clotting, thrombin instead converts a protein C, which is a serine protease, into its active form

70
Q

What type of molecule is protein C? What does it do?

A

Serine protease.

Binds to protein S, which degrades factor Va and VIIIa

71
Q

What is the function of protein S?

A

Binds to protein C, which degrades factors V and VIII

72
Q

What are the factors that the protein S/C complex degrades?

A

V and VIII

73
Q

What is the molecule that thrombin binds to, to activate protein C?

A

thrombomodulin

74
Q

What are the serpins?

A

Serine protease Inhibitors

75
Q

What type of molecules is antithrombin III? How does it work?

A

Serpin (serine protease inhibitor)

Binds and inhibits thrombin, factors IX, X, XI, and XIII

76
Q

The formation of antithrombin III is greatly enhanced by the presence of what chemical? How does this work?

A

Heparin binds to ATIII, and increases its affinity for thrombin

77
Q

What is the function of the TFPI protein?

A

produced by endothelial cells, and inhibits factor VII and Xa

78
Q

What is the pathophysiology of factor V leiden?

A

AA change leads to resistance to cleavage by protein C

79
Q

What is the process that down regulates coagulation factors?

A

Fibrinolysis

80
Q

What is the molecule that is responsible for fibrinolysis?

A

Plasmin

81
Q

What is the circulating form of plasmin? What organ produces this?

A

Plasminogen–liver

82
Q

Plasminogen has a high affinity for what molecule? What happen when it binds to this?

A

fibrin– gets incorporated into the developing clot

83
Q

What is the molecule that activates plasminogen into plasmin? What cells produce this?

A

tPA produced by endothelial cells

84
Q

Release of tPA is stimulated by what molecule? What else does this do to ensure that tPA is activated?

A

Protein C

Also degrades PAI-1 (which inhibits tPA)

85
Q

What is the function of PAI-1?

A

Inhibits tPA

86
Q

tPA has a high affinity for what molecule? Why is this important?

A

Fibrin

Goes to where plasminogen is

87
Q

What are the circulating proteins in the blood that ensure active plasmin does not break down clots throughout the body?

A

alpha2-antiplasmin

alpha2-macroglobulin

88
Q

What is the function of streptokinase?

A

Exogenous activator of plasminogen

89
Q

What does ADP trigger on platelets?

A

Conformation change of GP IIb/IIIa, allowing to bind fibrinogen

90
Q

Why do platelets fail to aggregate in bernard soulier syndrome?

A

Defect in the Gp-Ib

91
Q

Why do platelets fail to aggregate in Glanzmann thrombasthenia?

A

Defect in GpIIb/IIIa

92
Q

What do you add to the PT test to initiate the extrinsic pathway?

A

Tissue factor

93
Q

What is the only factor that is not produced by the liver? What is it produced by?

A

Factor VIII

Endothelial cells

94
Q

What is the function of the Ca that binds to gamma-carboxyglutamate?

A

Chelates Ca on phospholipids, keeping the factors near the site they’re needed

95
Q

Why are neonates given a Vit K shot?

A

Vit K produced by gut flora, of which neonates have none

96
Q

What are the components of the extrinsic Xase complex?

A

Factors VII and X

97
Q

What is the factor that factor X activates to generate the extrinsic pathway tenase complex?

A

Factor V

98
Q

What is the initial complex of proteins that sets off the intrinsic pathway? What is this called? What activates it?

A

Factor XI, prekallikrein, forming the HMWK

Carboxypeptidase on cell membrane activates it

99
Q

What is the effect of factor XIII?

A

Activated by thrombin

Will crosslink E and K residues on platelets

100
Q

What are the two factors that are inhibited by protein S?

A

8 and 5

Hematology (32 decks)

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