Coagulation Disorders - Exam 4 Flashcards

1
Q

What are the plt phases?

A

adhesion, aggregation, secretion, cross-linking of adjacent plts

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2
Q

What do we see in blood vessels with thrombogenesis?

A

vasoconstriction, formation of plt plugs, regulation of coagulation and fibrinolysis

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3
Q

What is the extrinsic pathway?

A

tissue damage exposes tissue factor

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4
Q

What is the intrinsic pathway?

A

plts interact with damaged endothelium

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5
Q

What do we see with thrombin activation?

A

formation of fibrin clot

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6
Q

Coagulation is also known as?

A

Thrombogenesis

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7
Q

What causes hemostasis or triggers it?

A

injury

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8
Q

What is involved with the intrinsic pathway, PTT or PT?

A

PTT

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9
Q

what is involved in the extrinsic pathway, PT or PTT?

A

PT

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10
Q

If collagen and vWF are exposed, what happens?

A

binds to receptors on the platelet 1

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11
Q

Where do we see DVT formed?

A

lower limbs, large veins

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12
Q

What is virchows triad?

A

stasis, endothelial injury and hypercoagulability

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13
Q

What do we see with white thrombus?

A

Found in high pressure arteries, obstruct arterial flow, downstream ischemia, plts and fibrin cross linking, abnormal endothelium

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14
Q

Is serotonin involved in vasoconstriction of blood vessels?

A

yes

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15
Q

what is another name for plt plugs?

A

thrombocytes

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16
Q

What is involved with red thrombus?

A

low pressure veins, red cells around white thrombus, long tail, detachment, pulmonary embolism

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17
Q

What are the inherited DVT risk factors?

A

antithrombin 3 deficiency, protein C deficiency, protein S deficiency, sickle cell anemia, activated protein C resistance

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18
Q

Does prostacyclin inhibit plt aggregation?

A

yes

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19
Q

Do NSAIDS inhibit or excite PGD synthesis?

A

inhibit

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20
Q

Acquired DVT risk factors

A

bedridden, surgery/trauma, obesity, estrogen use, malignancies, chronic venous insufficiency

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21
Q

What does exposed collagen bind to?

A

GP 1a

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22
Q

hat does exposed vWF bind to ?

A

GP 1b

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23
Q

what does aspirin inhibit>

A

TXA2

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24
Q

What holds plts together?

A

fibrinogen

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25
Q

what creates a spiderweb to link lots of plts together?

A

fibrin

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26
Q

What do we want to avoid with coagulation?

A

DIC and impaired blood flow

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27
Q

What results do we see with DIC?

A

generalized blood coagulatiom, excessive consumption of factors and plts, spontaneous bleeding

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28
Q

What causes DIC

A

massive tissue injury, malignancy, bacterial sepsis, abruptio placentae

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29
Q

how do we treat DIC?

A

plasma transfusions, underlying cause

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30
Q

what is the mortality with DIC

A

10-50%

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31
Q

What are the two major systems with coagulation regulation?

A

fibrin inhibition and fibrinolysis

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32
Q

what do protease inhibitors do?

A

rapidly inactivate coagulation proteins

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33
Q

4 protease inhibitors

A

a1-antiprotease
a2-macroglobulin
a2-antiplasmin
antithrombin

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34
Q

what does the fibrinolytic system do?

A

convert inactive plasminogen to plasmin

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35
Q

what is tPA released from?

A

injured cells

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36
Q

What does plasmin do?

A

remodels the thrombus and limits extension of the thrombus

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37
Q

What are 3 types of thrombotic disease therapy?

A

tissue plasminogen activator (t-PA)
urokinase
streptokinase

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38
Q

what does aminocaproic acid do?

A

protect clots from lysis

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39
Q

What do anticoagulants do?

A

inhibit the action or formation of clotting factors. prevent clot formation

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40
Q

what does plasmin do with fibrin?

A

creates fibrin split products

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41
Q

what do antiplatelets drugs do?

A

inhibit plt aggregation and prvent plt plugs

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42
Q

what do thrombolytic drugs do?

A

lyse existing clots

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43
Q

what do hemostatic or antifibrinloytic drugs do?

A

promote blood coagulation

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44
Q

What type of drug is heparin and what is its action?

A

anticoag, inactivates clotting factors

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45
Q

what type of drug is warfarin and what is the MOA?

A

anticoag, decrease synthesis of clotting factors

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46
Q

Type of drug is aspirin and MOA

A

antiplt and decrease plt aggregation

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47
Q

streptokinase is what kind of drug and MOA

A

thrombolytic and fibrinolysis

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48
Q

what do indirect thrombin inhbitors do?

A

enhance antithrombin activity, inactivate factor 10a, inhibit thrombin

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49
Q

what is the in depth MOA of heparin?

A

works on antithrombin 3, binds and activates AT, enhances activity, catalyzes reaction without being consumed

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50
Q

What is heparin extracted from?

A

porcine intestinal mucosa and bovine lung

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51
Q

Is LMW more or less effective on coagulation?

A

less effective

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52
Q

examples of LMW heparin

A

enoxaparin, dalteparin, tinzaparin

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53
Q

Toxicity associated w heparin

A

bleeding, transient thrombocytopenia (HIT)

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54
Q

Who is more prone to hemorrhage with heparin?

A

elderly women and pts with renal failure

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55
Q

What lab tests to monitor w heparin?

A

PT, aPTT

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56
Q

What reverses heparin

A

protamine sulfate

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57
Q

is protamine sulfate useful for LMW?

A

not really

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58
Q

what is time to clot?

A

PT

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59
Q

time to clot compared to control

A

INR

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60
Q

what is PT assessing?

A

function of extrinsic pathway and common pathway

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61
Q

What does aPTT measure?

A

activity of the intrinsic system and common pathway

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62
Q

contraindications for heparin

A

active bleeding, hemophilia, TCP, severe HTN, intracranial hemorrhage, infective endocarditis, active TB, GI ulcers, advanced hepatic disease

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63
Q

Pentasaccharide molecule of heparin

A

fondaparinux

64
Q

what is fondaparinux useful for?>

A

HIT

65
Q

What do we add into PT?

A

tissue factor - factor 3

66
Q

What do direct thrombin inhibitors bind to?

A

active and substrate or thrombin active sites

67
Q

what direct thrombin inhibitors bind to thrombin active sites?

A

argatroban, dabigatran

68
Q

what direct thrombin inhibitors bind to active and substrate recognition sites of thrombin?

A

hirudin

69
Q

What is normal INR?

A

1

70
Q

Another name for warfarin?

A

coumadin

71
Q

What INR do we want with heparin?

A

3

72
Q

What type of drug is warfarin?

A

anticoag

73
Q

how much protein binding with warfarin?

A

99%

74
Q

what is the MOA of warfarin?

A

blocks the gamma carboxylation of glutamat residues

75
Q

do we wean to heparin or wean to warfarin?

A

warfarin

76
Q

what is the delay for warfarin?

A

8-12 hr

77
Q

toxicity with warfarin? Associated with babies and adults

A

hemmorhagic disorder in fetus, birth defects, cutaneous necrosis

78
Q

what is the therapeutic range of warfarin defined by?

A

INR

79
Q

How much reduction of PT activity with warfarin?

A

25% of normal

80
Q

warfarin INR target range?

A

2-3

81
Q

What are the pharmacokinetic interactions with warfarin?

A

enzyme induction, enzyme inhibition, reduced plasma protein binding

82
Q

What are the pharmacodynamic interactions with warfarin?

A

synergism, competitive antagonism, and altered vitamin K

83
Q

How do we reverse warfarin?

A

stop drug, vitamin K, FFP, factor 9 concentrates

84
Q

what do fibrinolytics do?

A

rapidly lyse thrombi, cataylze the formation of serine protease plasmin

85
Q

epoxide goes to what?

A

quinone

86
Q

what enzyme makes epoxide go to quinone and hydroquinone?

A

VIT K reductase

87
Q

what does quinone go to?

A

hydroquinone

88
Q

drug class of streptokinase

A

fibrinolytics

89
Q

what is streptokinase synthesized by

A

streptococci

90
Q

what is urokinase synthesized by?

A

the kidney

91
Q

how does urokinase work on clots?

A

lyses thrombus from within

92
Q

what is the recombinant form of t-PA

A

Alteplase

93
Q

what does T-PA activate?

A

activates plasminogen bound to fibrin

94
Q

what does t-PA do with finbronolysis

A

confines it to the formed thrombus

95
Q

does t-PA avoid or interact with systemic activation?

A

avoids

96
Q

what type of COX inhibitor is aspirin

A

COX1

97
Q

does aspirin work on thromboxane 2?

A

yes

98
Q

what effects do we see on the plt when aspirin is given?

A

shape changes, grnaule release change, aggregation changes

99
Q

when we inhibit TXA2 synthesis, what changes?

A

bleeding time

100
Q

what does clopidogrel work on?

A

plt aggregation

101
Q

MOA of plavix

A

irreversibily inhibit ADP receptor on plts

102
Q

what is reduction % of ischemic events w plavic compared to aspirin?

A

8.7%

103
Q

2b and 3a receptor blockers are what kind of drugs?

A

antiplt - inhibit plt aggregation

104
Q

abciximab is what kind of receptor blocker and what kind of drug?

A

2b and 3a, mab

105
Q

where do we get vit k

A

leafy green veggies and gut bacteria

106
Q

where does vit k work on the clotting cascade?

A

PT and factors 7,9,10

107
Q

deficiencies in plasma coag factors

A

hemophilis, AT 3 deficiency

108
Q

what factor does desmopressin acetate work on?

A

factor 8

109
Q

what does desmopressin acetate cause

A

mild hemophilia and vo Willebrand disease

110
Q

what does aminocaproic acid competitively inhibit?

A

plasminogen becoming plasmin

111
Q

when do we use aminocaproic acid?

A

hemophilia therapy, bleeding from fibrinolytic therapy, intracranial aneurysms, post surgical bleeding

112
Q

when do we use TXA

A

trauma, heavy period bleeding, postpartum, epistaxis

113
Q

what is the MOA of TXA

A

antifibrinolytic, inhibits the conversion of plasminogen to plasmin

114
Q

are NSAIDs proclot?

A

yes

115
Q

what does aspirin target?

A

the plt itself, it is an exception to the NSAIDs

116
Q

what type of feedback is thrombogenesis?

A

positive feedback

117
Q

what does plt 1 release?

A

thromboxane, 5ht, adp

118
Q

where do the released substances bind?

A

to their respective receptors on the next plt

119
Q

when the coag substances bind to the next plt, what happens to the cell?

A

it degranulates

120
Q

What holds plts together?

A

fibrinogen

121
Q

how is fibrinogen produced?

A

coag cascade

122
Q

less thromboxane does what with # of clots?

A

decreases # of clots

123
Q

Where do the extrinsic and intrinsic pathway meet?

A

at the common pathway

124
Q

what does Xa activate?

A

Prothrombin to thrombin

125
Q

does thrombin create more thrombin?

A

yes

126
Q

does thrombin activate plts?

A

yes

127
Q

can thrombin become fibrinogen?

A

yes

128
Q

who makes fibrin?

A

fibrinogen

129
Q

what is the common pathway?

A

thrombin activation

130
Q

who does tissue factor activate?

A

factor 7

131
Q

What causes tissue factor to be activated?

A

trauma

132
Q

what does factor 7a activate?

A

factor 10a

133
Q

what does a mean?

A

activated form

134
Q

does tissue factor help activate factor 10a?

A

yes

135
Q

who does factor 10a activate?

A

thrombin

136
Q

what is the factor number for thrombin?

A

2a

137
Q

thrombin activates what?

A

fibrin, 1a

138
Q

What does the intrinsic pathway target?

A

The endothelial cell lining

139
Q

damage to endothelial cell lining activates what factor?

A

factor 12

140
Q

factor 12 activates what factor?

A

factor 11

141
Q

Factor 11 activates what factor?

A

factor 9a

142
Q

T or F: the intrinsic pathway uses factor 10a to convert prothrombin to thrombin?

A

True

143
Q

what factor can fibrin be cross linked with?

A

factor 13

144
Q

is the cross-linked fibrin clot the ideal or worst option?

A

ideal

145
Q

What other factor does thrombin activate to help the formation of more thrombin?

A

factor 5

146
Q

what other factor does thrombin work on besides factor 5 and fibrin?

A

factor 8

147
Q

is factor 8 necessary?

A

no

148
Q

if your factor 8 deficient

A

hemophilia type A

149
Q

T or F: Thrombin activates protein C and thrombomodulin

A

true

150
Q

Protein C and protein S inhibit what two factors?

A

factor 5 and factor 8

151
Q

is protein C and protein S a negative or positive feedback?

A

negative

152
Q

is antithrombin part of the negative feedback loop or positive feedback loop?

A

negative

153
Q

where are all of the factors made?

A

the liver

153
Q

What does plasmin do with fibrinogen?

A

creates degradation products

154
Q

what does antithrombin work on?

A

factor 10 and thrombin

155
Q

what is the proactivator of streptokinase?

A

anistreplase

156
Q

Factor Xa inhibitors

A

eliquis and xarelto (apixaban and rivaroxaban)