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SUM '20 - Pharm II > Procoagulants > Flashcards

Procoagulants Flashcards

1
Q

name the two synthetic antifibrinolytic agents available (lysine analogs)

A

epsilon aminocaproic (EACA)

tranexamic acid (TXA)

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2
Q

antifibrinolytic agents- such as EACA and TXA competitively inhibit activation of?

A

plasminogen to plasmin

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3
Q

EACA has been removed from many european countries D/t?

A

safety concerns

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4
Q

when comparing aprotinin, EACA, TXA -what is the MI risk

A

no risk

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5
Q

aprotinin, EACA, TXA were effective in reducing the need for

A

RBC transfusions

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6
Q

specifically aprotinin was effective in reducing

A

need for reoperation d/t bleeding

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7
Q

aprotinin, TXA, EACA have also reduced blood loss during ____surgeries

A

orthopedic surgeries

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8
Q

what is the function of plasmin

A

breaks down fibrin clots

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9
Q

what does TXA inhibit

A

plasminogen- which limits plasmin that breaks down coagulated functions

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10
Q

at higher doses what does TXA inhibit

A

plasmin

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11
Q

TXA dosing

loading and scheduled

A

1g/10min

1g/8hrs

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12
Q

oral TXA is used in the US for

A

heavy menstrual bleeding

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13
Q

TXA potential complications include

A

seizures:

TXA blocks GABA receptors in frontal cortex is thought to be the moa

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14
Q

what is aprotinin

A

polypeptide serine protease inhibitor

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15
Q

*what does aprotinin inhibit

A

plasmin and other serine proteases

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16
Q

when are we allowed to give aprotinin since it is removed from the market

A

available for compassionate use.

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17
Q

*in which situation is aprotinin used as an investigational drug under a special treatment protocol

A

in patients undergoing CABG surgery. it has been shown to decrease the need for RBC transfusion

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18
Q

*what does canada use aprotinin for

A

basic cabg surgery. but poor outcomes noted from higher risk cardiovascular surgeries. canada sites benefits outweigh risk

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19
Q

what is protamine

A

polypeptide containing approximately 70% arginine residues

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20
Q

*what medication is the only available reversal agent for UFH

A

protamine (polypeptide)

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21
Q

why do most patients receive too much protamine

A

plasma levels of heparin decrease overtime. and the protamine dose is not accounted for in the dosing

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22
Q

*excess protamine can contribute to

A

coagulopathy

& prolongs ACT

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23
Q

*how does protamine increase(wouldn’t it be decrease??) coagulation

A

inhibits platelets and serine proteases

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24
Q

oddly enough- excess protamine prolongs what level? and causes additional platelet dysfunction

A

ACT!

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25
Q

when protamine is given in the exact amount needed to reverse circulating heparin what is the act value

A

produces the lowest act values

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26
Q

when can heparin rebound occur

A

after initial reversal

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27
Q

when is heparin rebound observed

A

2-3 hours after first dose of protamine when pt is in ICU

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28
Q

the initial dose of protamine produces a

A

large drop in ACT time

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29
Q

if exact dose of protamine is not given, what may ensue

A

coagulopathy

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30
Q

a repeat dose of protamine may well be less than

A

50mg commonly administered

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31
Q

most patients may not need additional protamine

A

within 30 minutes of initial administration

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32
Q

the ACT is not a sensitive indicator of low heparin concentrations because…

A

platelet counts and fibrinogen levels may also affect values

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33
Q

protamine adverse reaction include (4)

A

anaphylaxis
acute pulmonary vasoconstriction (PHTN)
RV failure
hypotension

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34
Q

patients at an increased risk for adverse reactions are sensitized from exposure to the neutral protamine -where do patients get exposure to protamine

A

NPH

make up

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35
Q

Other patients at risk for protamine reactions include

A

vasectomy
drug allergies
prior exposure (eye make up/ mascara?)

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36
Q

DDAVP is an arginine vasopressin analog of

A

V2

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37
Q

what specific surgical patient might benefit from DDAVP

A

not clear

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38
Q

dose of DDAVP

A

0.3mg/kg over 15-30 minutes to avoid hypotension

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39
Q

what is the most frequently inherited bleeding disorder

A

VWD

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40
Q

ddavp may stimulate release of vWF

A

effect is likely minimal except in type 1 (maybe 2a)

*Type 3 and severe types 1 and 2, dDAVP is NOT EFFECTIVE

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41
Q

fibrinogen (1) synthesized where

A

in the liver

42
Q

half life of fibrinogen is

A

3.7 days (4 days)

43
Q

what do the platelets do with clot formation

A

enmeshed within the fibrin strands stabilizing the growing clot

44
Q

fibrinogen acts as the binding site for glycoprotein IIb /IIIa receptors - found on platelet surface which are

A

responsible for platelet aggregation.

45
Q

cross linking of fibrin polymers induced by what factor

A

XIIIa

46
Q

factor XIIIa is fundamental to the coagulation process increasing elasticity of the clot and its resistance to

A

fibrinolysis

47
Q

what is the binding site for glycoprotein IIb/IIIa receptor

A

fibrinogen

48
Q

Fibrinogen also acts as the binding site (ligand) for glycoprotein IIb/IIIa receptors found on platelet surface which are responsible for

A

platelet aggregation

49
Q

what substance is key to normalizing clotting function

A

fibrinogen supplementation

50
Q

*what is the underregocnized coagulation factor that is critical for producing effective clot in surgical patients

A

fibrinogen

51
Q

normal levels of fibrinogen

A

200-400 mg/dL

52
Q

when do we expect fibrinogen to be elevated

A

greater than 400 m/dL in pregnancy

53
Q

what is the important final step in clot formation

A

plasma XIII- stabilizes initial clot

54
Q

what relationship does post operative blood loss have for factor XIII in cardiopulmonary bypass

A

inverse relationship

55
Q

recombinant activated factor VIIa is

A

recombinant rFVIIa (7)

56
Q

rFVIIa is approved for

A

hemophilia but known for off label use to procoagulant in massive hemorrhage

*

57
Q

1 unit of cryoprecipitate per 10kg increases fibrinogen by

A

50-70mg/dl

58
Q

in CABG- more factor XIII=

in CABG less factor XIII=

A

more factor XIII=less blood loss

Less factor XIII=more blood loss

59
Q

• Warfarin reversal in the US is typically achieved

A

with FFP

60
Q

most other countries use ___for warfarin reversal

A

PCC’s

61
Q

Gelatin sponges (Gelfoam) what is it made from

A

purified pork skin gelatin- increases contact activation helps create topical clot

62
Q

Surgicel or Oxycel

A

oxidized regenerated cellulose works like gelfoam

*work like gelfoam

63
Q

where should gelatin foam NOT be used near

A

nerves or in confined spaces

64
Q

when is coseal used

A

where swelling and expansion are not a concern

65
Q

what has been used in cardiac surgery

A

bioglue

66
Q

• BioGlue has been used in cardiac surgery but it contains a glutaraldehyde component

A

Cross-links proteins to fix tissues it is applied to

67
Q

bovine thrombin should be avoided due to its potential for

A

anti-bovine thrombin antibody formation and immune mediated coagulopathy

cow=bovine have allergic reactions

68
Q

where is unfractionted heparin extracted from

A

porcine (pig)intestine the majority or bovine (cow) lungs where heparin is stored in mast cells.

69
Q

how are anticoagulant effects are produced by binding to

A

Anti thrombin (AT) previously known as at 3

70
Q

heparin binds to AT enhancing the rate of thrombin at complex formation by how many times

A

1,000-10,000

71
Q

how many fold increase in the risk for VTE

A

20 fold

72
Q

in general surgery patients - what is the DVT % incidence

A

10-40%

73
Q

name the 4 surgery categories that have the higher risk for DVT

A

orthopedic
thoracic
cardiac
vascular

74
Q

general surgery have a higher risk of

A

DVT

75
Q

in patients with renal failure or renal dysfunction- are heparin and warfarin affected?

A

minimally- due to non renal clearance

76
Q

who has a risk of DVT higher than general surgery

A

hip surgery

77
Q

DANAPAROID—Orgaran (LMWH)

no longer used in the US- due to?

A

shortage but used in other countries

78
Q

danaparoid-orgaran how does it work?

A

this low molecular weight heparinoid compound attenuates fibrin formation by binding to AT

79
Q

danaparoid- orgaran derived from procaine intestinal mucosa consisting of a mixture of

A

dermatan sulfate and chondroitin sulfate.

80
Q

danaparoid -orgaran is eliminated

A

primarily in the kidneys

81
Q

fondaparinux -Arixtra-metabolism occurs

A

metabolism Does not Occur! but it is eliminated by the kidneys and should not be used in patients with renal dysfunction

82
Q

clinical uses of fondaparinux- arixtra

A

DVT
PE
alternative treatment for Hit positive

83
Q

what factor does fondaparinux arixtra inhibit

A

Xa-stuart-has no direct activity against thrombin

84
Q

if patient has renal failure what type of heparin do we use

A

LMWH is greatly prolonged in renal failure.

UFH should be used in kidney failure

85
Q

for protection against venous thromboembolism in high risk medical and surgical patients- its thought to be better treated with

A

LMWH than heparin

86
Q

what are the two commonly administered LMWH

A

enoxaparin and dalteparin

87
Q

what pharmacokinetics of enoxaparin and dalteparin between patient are more consistent than heparin- why

A

because they bind less to proteins than does heparin

88
Q

where do we find protamine

A

salmon sperm

89
Q

what charges is protamine and heparin

A

protamine is positively charged alkaline

combines with the negatively charged acidic heparin to form a stable complex that is devoid of anticoagulant activity

90
Q

protamine dosing example

A

o Example from class: If you gave 10,000 units 1 hour ago how much will you give? 5,000 units will be circulating (1 mg for every 100 units) so = 50 mg

91
Q

protamine dose 1mg for how much heparin circulatin

A

1mg for every 100 units of heparin circulating

92
Q

what is the half life of heparin

A

1 hours

93
Q

if there is an immediate reaction to heparin what should be suspected

A

HIT

94
Q

• For cardiac surgery, a baseline ACT is determined:

A

(before & 3 min after administration and 30 min intervals thereafter)

95
Q
  • Treating Fibrinogen Deficiency is important for survival and has a POSITIVE correlation with reductions in mortality of trauma patients.
  • Consider transfusion before fibrinogen drop to
A

< 100 mg/dL may not be fixed by FFP.

96
Q

PCC’s are concentrations of coagulation factors that include factors:

A

K-1972

II, VII, IX, X

97
Q

Two PCC used worldwide are KCENTRA and Octaplex. the MOA :

A

Vit K antagonist-induced (Warfarin) reversal

98
Q

3 other PCC approved in the usa for hemophilia are Feiba VH, Profilnine SD, Bebulin VH. These contain mainly what factor:

A

Factor IX (9)

99
Q

PCC’s are recommended in guidelines are primary treatement of reversal in patients with:

A
  • Life threatening bleeding

- and increased INR when URGENT REVERSAL IS REQUIRED

100
Q

these agents are used intraoperatively to promote hemostasis at the site of vascular injury

A

Topical hemostatic agents

101
Q

Currently there are 2 human thrombins available for

A

clinical use:

  1. plasma derived thrombin
  2. recombinant human thrombin

SUM '20 - Pharm II (30 decks)

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