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Perf Tech II (exam 1) > Topic 3 - Heparin Neutralization > Flashcards

Topic 3 - Heparin Neutralization Flashcards

1
Q

Protamine derived from?

A

salmon sperm

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2
Q

Protamine - is a?

A
  • polycationic polypeptide protein (67%arginine)

- strongly alkaline with numerous positive charges

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3
Q

Protamine binds with Heparin to form?

A

a stable salt precipitate

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4
Q

Heparin-Protamine Clearance current theory

A

its cleared by the reticuloendothelial system

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5
Q

RES (reticuloendothelial cystem)

A

responsible for clearing stuff
consists of monocytes, macrophages(macrophage are circulating monocytes), tissue histiocytes and Kupffer cells(located in liver, spleen and lymph nodes)

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6
Q

RES is now referred to as?

A

MPS - mononuclear phagocyte system

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7
Q

Protamine as insulin? (2 kinds)

A
  • Neutral Protamine Hagedorn insulin(NPH)
    T1/2 like 24hours
  • Protamine-Zinc insulin (PZI)
    T1/2 about 36 hours
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8
Q

Viable alternative to Protamine?

A

THERE IS NO Viable Alt to Protamine

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9
Q

anticoagulation effect of protamine ?

A

becomes clinically significant at doses 3X amount needed for heparin neutralization
- effect clinically significant only when large amounts given

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10
Q

Anticoagulation effect of protamine seen at what doses?

A

at excess protamine doses of 6-15mg/kg

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11
Q

Anticoagulation effect of protamine caused by?

A

inhibition of platelet induced aggregation by the heparin-protamine complex

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12
Q

Protamine dose most patients should tolerate

A

1-2mg/kg w/out adverse effects effects on hemostasis

our normal values calculation is 1-1.3mg/kg

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13
Q

Lower doses of protamine tend cause? (3)

A
  • cause less chest tube drainage
  • provides for higher platelet counts
  • more normalized clotting times
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14
Q

Methods of Calculating Protamine dose (4)

A
  • Fixed dose
  • ACT/heparin dose response curve
  • heparin concentration
  • protamine titration
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15
Q

Fixed dose method for calculating Protamine

A

give fixed dose of protmine for each unit of heparin that was given
- norm 1-1.3mg per 100units of heparin

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16
Q

Heparin ACT Dose Response Curve method for calculating Protamine

A

Plot pre and post heparin ACT, plot curve and determine slope. Measure ACT after termination
Calculates total heparin load
dose usually 1.3mgs per 100units of total heparin load

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17
Q

Heparin Concentration method for calculating Protamine done where?

A

must be done in the laboratory

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18
Q

Heparin Concentration method for calculating Protamine advantages

A

consistently results in lower protamine dose versus ACT response curve

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19
Q

Heparin Concentration method for calculating Protamine disadvantages

A

takes time so not always good correlation of actual concentrations and clotting times
have to estimates pt plasma volume

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20
Q

Protamine Titration method for calculating Protamine

A
  • Tubes of various dilutions of a protamine solution, fixed volume of hepranized whole blood added to each tube
  • tube with lowest concent/shortest clotting time is best representation
  • Actual protamine dose calculated bases on assumed neutralization ratio
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21
Q

Protamine Titration method for calculating Protamine advantages

A
  • usually give less protamine than fixed dose
  • less post op bleeding
  • less exposure to blood products
  • absence of heparin rebound
22
Q

Protamine Titration method for calculating Protamine disadvantages

A
  • estimation of patient’s blood volume

- variability of heparin and protamine preparations

23
Q

How does the Heparin-Protamine complex activated the complement cascade?

A

via the classical pathway

24
Q

Adverse Protamine Reaction - reaction classification 1, Type 1

A
  • Mild hypotension due to histamine release(rapid infusion)
  • Can be ameliorated by giving protamine intra-arterial(intra-aortic) (bc it then goes straight to the lungs, most mast cells tend to live in the respiratory tract, so its a way to prevent reaction
25
Q

Histamine does what? (5)

A
  • increase sensitivity to pain and itching
  • dilation of arterioles and precapillary sphincters
  • increased HR (both direct and reflex effect)
  • most bronchoconstriction
  • increase GI motility
26
Q

Cromolyn sodium is?

A

a mast cell membrane stabilizer and helps prevent mast cell degranulation before its occurrence

27
Q

Adverse Protamine Reaction - reaction classification 1, Type IIa

A

True anaphylaxis; IgE mediated. Anamnestic response(means memory of the immune system)

28
Q

Adverse Protamine Reaction - reaction classification 1, Type IIa – systemic effects?

A

Decrease SVR, PA, LA, & RA pressures +/- bronchospasm

29
Q

Adverse Protamine Reaction - reaction classification 1, Type IIb

A

Immediate anaphylactoid; No IgE involvement

Mediated by thromboxane

30
Q

Adverse Protamine Reaction - reaction classification 1, Type IIb - systemic effects

A

leads to pulmonary vasoconstriction and bronchoconstriction

31
Q

Adverse Protamine Reaction - reaction classification 1, Type IIc

A
  • delayed Anaphylactoid
  • increased post-op pulmonary edema
  • also related to complement activation with histamine/thromboxane/ect release
32
Q

Adverse Protamine Reaction - reaction classification 1, Type III occurs in what % of population

A

BAD ONES
Occurs in .6% of adult cardiac surgical patients
No long term negative sequelae

33
Q

Adverse Protamine Reaction - reaction classification 1, Type III effects

A
  • Catastrophic pulmonary vasoconstriction (IgG/complement-mediated) seems to be thromboxane-mediated
  • Noncardiogenic pulmonary edema
34
Q

Adverse Protamine Reaction - reaction classification II, Type A

A

Pharmacologic histamine release

35
Q

Adverse Protamine Reaction - reaction classification II, Type B

A

True anaphylaxis (IgE mediated)

36
Q

Adverse Protamine Reaction - reaction classification II, Type C

A
  • Anaphylactoid thromboxane release
  • Pulmonary vasoconstriction
  • Bronchoconstriction
37
Q

Fish allergy what % of population?

A

up to 27% of general population

  • risk factor to having an adverse reaction to Protamine
38
Q

Antibody development can occur from prior exposure in…? (4)

(aka Risk factors to having an adverse reaction to Protamine)

A
  • re-op patients
  • dialysis patients
  • Neutral protamine Hagedorn(NPH) Insulin preparation
  • Heparin/Protamine in Cath lab
39
Q

What is the Increase in True allergic response..

when patient has had prior reaction to protamine?

A

Increase 189x

40
Q

What is the Increase in True allergic response..

when patient has fish allergy ?

A

increase 24.5X

41
Q

What is the Increase in True allergic response..

when the patient has exposure to NPH insulin?

A

Increase 8.2X

42
Q

What is the Increase in True allergic response..

when patient has allergy to any drug?

A

Increase 3X

43
Q

What is the Increase in True allergic response..

when patient has prior exposure to protamine?

A

No increase

44
Q

Neutral Protamine Hagedorn insulin

A

Protamine added to regular insulin

45
Q

Suggested Rate of Protamine administration

A

no faster than 5mg/min (although 15mg/min might be more common)

46
Q

Alternatives to Protamine? (7)

A
  • allow heparin to be metabolized
  • Platelet concentrates
  • Hexadimethrine
  • Intra-aortic protamine injections
  • Heparinase I
  • Lactoferrin
  • Heparin-Removal devices
47
Q

Platelet concentrations (that you give)

A

alternative to protamine (don’t work that well)

  • PF4 released from actived platelets combines with and neutralizes protamine
  • Does not restore coagulation following bypass
  • Recombinant form failed clinical trials
48
Q

Hexadimethrine

A

alt to protamine

  • Synthetic polycation
  • has probs with renal toxicity
  • can produce pulmonary vasoconstriction if given to quickly
  • use to avoid true allergic reactions
49
Q

Lactoferrin

A

alternative to protamine

Demonstrated modest neutralizing capacity

50
Q

Protamine resistance

Classification 1, typeII, a, b, and c

A

a - True anaphylaxis; IgE mediated. Anamnestic. Decrease SVR, PA, LA, & RA pressures +/- bronchospasm ~50% of IDDM patients taking NPH insulin have antiprotamine IgE
b - Intermediate anaphylactoid, No IgE involvement
c - Delayed Anaphylactoid; Increased post-op pulmonary edema

51
Q

Protamine adverse reaction, classification II, type A, B, C

A

A - Pharmacologic histamine release
B - True anaphylaxis (IgE mediated)
C - Anaphylactoid thromboxane release; Pulmonary vasoconstriction; Bronchoconstriction

Perf Tech II (exam 1) (9 decks)

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