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Hemostasis Flashcards

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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
Defect in GpIb/vWF = what disease?
Bernard-Souilier
26
Defect in GP IIa/IIIb results i what disease?
glanzmann thrombasthenia
27
Decreased vWF = what disease?
von Willebrand disease
28
What is the convergence point of the coagulation cascades?
factor X
29
Why is the extrinsic pathway named as such?
Exogenous material (tissue factor) was needed to activate it
30
Which pathway is activated upon exposure to negatively charged surfaces?
intrinsic pathway
31
What are zymogens?
inactive precursors of proteins
32
factor I = ? Where is it produced?
Fibrinogen, liver
33
factor II = ? Where is it produced?
Prothrombin Liver
34
factor III = ? Where is it produced?
Tissue factor | Most everywhere
35
factor VI = ? Where is it produced?
Ca
36
factor V= ? Where is it produced?
Proaccelerin Liver
37
factor VI = ? Where is it produced?
no such thing
38
factor VII = ? Where is it produced?
Proconvetrin
39
What are the factors that need vit k to function? What is the molecule that they all have in common that needs vit K?
10, 9, 7, 2 | gamma carboxyglutamate
40
What is the enzyme that requires vitamin K as a cofactor?
Carboxylase
41
What is endothelin, and what does it do?
Local factor produced by endothelial cells that causes vasoconstriction
42
What is the cement part of the clot?
Fibrin
43
Do platelets have RNA?
Small amount
44
What is the mineral that is secreted by platelets that causes activation of the coag cascade?
Ca
45
What is the cytokine that triggers the change in conformation of GpIIb/IIIa to allow for the receptor to bind to fibrinogen?
ADP
46
What is the basis of the partial thromboplastin time test?
Intrinsic pathway will clot with exposure to negative charges on glass
47
What is the purpose of the gamma carboxyglutamate on factors 10, 9, 7, and 2?
Chelates Ca a lot better than glutamate does, allowing for Ca ions to coordinate negatively charged lipid membranes and keeping them bound
48
What is the enzyme that is inhibited by warfarin? What does this do?
Vitamin K epoxide reductase, prevents Vitamin K from being reduced back to its usable form
49
What type of molecule is factor 7? What does it do?
Serine protease that cleaves factor X, another serine protease
50
What type of molecule is factor 10?
Serine protease
51
factor Xa catalyzes the slow or fast cleavage of prothrombin?
Slow
52
What type of molecule is factor X? What is its function?
Serine protease, that cleaves factor V
53
What are the two components of the prothrombinase complex? What does this do?
Factors V and X | cleaves prothrombin rapidly
54
What are the three major functions of thrombin?
1. Cleave fibrinogen 2. activates factor V and VII (positive feedback 3. Activate factor VIII (intrinsic pathway)
55
What is the test that is used to assess the intrinsic pathway?
PTT
56
What is the first factor that is activated in the intrinsic pathway? How?
Factor XII by exposure to negatively charged surfaces
57
What are the two factors that factor XII activates? What is this factor complexed with?
Factor XI, which is complexed with prekallikrein to form a high molecular weight kininogen (HMWK)
58
What is the factor that factor XI activates?
factor IX
59
What is the factor that factor IX activates? Is this a fast or slow reaction?
factor X, slow
60
Thrombin cleaves what factor
VIII
61
What are the factors that form the intrinsic tenase complex? What is the function of this complex?
VIII, IX. Rapid activation of factor X
62
What is the factor that must be activated to form the hard clot? What type of molecule is this?
XIII | transglutaminase
63
What is the amino acid bond that factor XIII catalyzes in fibrin?
K to a E
64
What is the mode of inheritance for hemophilia A and B?
xLR
65
What is the most common hemophilia?
A
66
What is the pathophysiology of hemophilia A?
deficiency of factor 8 production
67
What is the pathophysiology of hemophilia B?
Deficiency of factor IX production
68
What is the treatment for hemophilia A and B?
Recombinant factor (8 or 9 for A and B respectively)
69
How does thrombin inhibit clotting?
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
What type of molecule is protein C? What does it do?
Serine protease. Binds to protein S, which degrades factor Va and VIIIa
71
What is the function of protein S?
Binds to protein C, which degrades factors V and VIII
72
What are the factors that the protein S/C complex degrades?
V and VIII
73
What is the molecule that thrombin binds to, to activate protein C?
thrombomodulin
74
What are the serpins?
Serine protease Inhibitors
75
What type of molecules is antithrombin III? How does it work?
Serpin (serine protease inhibitor) Binds and inhibits thrombin, factors IX, X, XI, and XIII
76
The formation of antithrombin III is greatly enhanced by the presence of what chemical? How does this work?
Heparin binds to ATIII, and increases its affinity for thrombin
77
What is the function of the TFPI protein?
produced by endothelial cells, and inhibits factor VII and Xa
78
What is the pathophysiology of factor V leiden?
AA change leads to resistance to cleavage by protein C
79
What is the process that down regulates coagulation factors?
Fibrinolysis
80
What is the molecule that is responsible for fibrinolysis?
Plasmin
81
What is the circulating form of plasmin? What organ produces this?
Plasminogen--liver
82
Plasminogen has a high affinity for what molecule? What happen when it binds to this?
fibrin-- gets incorporated into the developing clot
83
What is the molecule that activates plasminogen into plasmin? What cells produce this?
tPA produced by endothelial cells
84
Release of tPA is stimulated by what molecule? What else does this do to ensure that tPA is activated?
Protein C Also degrades PAI-1 (which inhibits tPA)
85
What is the function of PAI-1?
Inhibits tPA
86
tPA has a high affinity for what molecule? Why is this important?
Fibrin Goes to where plasminogen is
87
What are the circulating proteins in the blood that ensure active plasmin does not break down clots throughout the body?
alpha2-antiplasmin | alpha2-macroglobulin
88
What is the function of streptokinase?
Exogenous activator of plasminogen
89
What does ADP trigger on platelets?
Conformation change of GP IIb/IIIa, allowing to bind fibrinogen
90
Why do platelets fail to aggregate in bernard soulier syndrome?
Defect in the Gp-Ib
91
Why do platelets fail to aggregate in Glanzmann thrombasthenia?
Defect in GpIIb/IIIa
92
What do you add to the PT test to initiate the extrinsic pathway?
Tissue factor
93
What is the only factor that is not produced by the liver? What is it produced by?
Factor VIII Endothelial cells
94
What is the function of the Ca that binds to gamma-carboxyglutamate?
Chelates Ca on phospholipids, keeping the factors near the site they're needed
95
Why are neonates given a Vit K shot?
Vit K produced by gut flora, of which neonates have none
96
What are the components of the extrinsic Xase complex?
Factors VII and X
97
What is the factor that factor X activates to generate the extrinsic pathway tenase complex?
Factor V
98
What is the initial complex of proteins that sets off the intrinsic pathway? What is this called? What activates it?
Factor XI, prekallikrein, forming the HMWK Carboxypeptidase on cell membrane activates it
99
What is the effect of factor XIII?
Activated by thrombin | Will crosslink E and K residues on platelets
100
What are the two factors that are inhibited by protein S?
8 and 5

Hematology (32 decks)

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