Topic 3 Flashcards Preview

Perf Tech > Topic 3 > Flashcards

Flashcards in Topic 3 Deck (55)
Loading flashcards...
1
Q

Protamine-

A ____ ____ protein that’s ___% arginine

A

polycationic polypeptide
67%
-Derived from salmon sperm

2
Q

Protamine-

Strongly ____ with numerous _____ charges

A

alkaline

positive

3
Q

Protamine-

Two active sites. Binds with heparin to form a

A

stable salt precipitate

4
Q

Protamine-

Neither heparin or protamine have an

A

anticoagulant effect once conjoined

5
Q

Protamine-

Produces mild

A

anticoagulant effect independent of heparin

6
Q

Heparin-Protamine Clearance

A

Reticuloendothelial System

7
Q

Reticuloendothelial System (RES)=

A

Consists of monocytes, macrophages, tissue histiocytes and Kupffer cells located in the liver, spleen, and lymph nodes

  • Responsible for clearing “stuff”
  • Kind of a “diffuse” part of the immune system
8
Q

Reticuloendothelial System is now known as the

A

Mono-nuclear Phagocyte System (MPS)

9
Q

Other Protamine Uses

A
  1. Neutral Protamine Hagedorn insulin (NPH)
  2. Protamine-Zinc insulin (PZI)
  3. Exploration into antineoplastic uses since it inhibits neovascularization
  4. Possible future gene therapy uses involving viruses
10
Q

No viable ______ to protamine exists (yet)!

A

alternative

11
Q

Anticoagulation Effect of Protamine-

Effect becomes clinically significant at doses

A

3 times amount needed for heparin neutralization

12
Q

Anticoagulation Effect of Protamine-

Anticoagulant effect clinically significant only when

A

large amounts of protamine given

13
Q

Anticoagulation Effect of Protamine-

Seems to be caused by

A

inhibition of platelet-induced aggregation by the heparin-protamine complex

14
Q

Recent evidence demonstrates protamine has ___ ____ effect on platelet aggregation; it makes platelets ____ ______ to the “triggers” released by other platelets (such as ADP, thromboxane)

A

no direct

less sensitive/insensitive

15
Q

Anticoagulant effect seen at excess protamine doses of

A

6 to 15 mg/kg

16
Q

Most patients should tolerate an excess protamine dose of

A

1 to 2 mg/kg without adverse effects on hemostasis

17
Q

Protamine overdose can cause

A

platelet dysfunction which can last for several hours

18
Q

lower doses of protamine tend to cause

A

less chest tube drainage
provides for higher platelet counts
“more” normalized clotting times

19
Q

The dose of protamine necessary to neutralize heparin is different—often significantly different–

A

in vitro as compared to in vivo

20
Q

Both heparin and protamine are biologic preparations and vary widely in

A

potency

21
Q

Since heparin is continuously metabolized, the required dose of protamine

A

decreases over time

22
Q

Calculation of Protamine Dose methods:

A

Fixed dose
ACT/heparin dose-response curve
Heparin concentrations
Protamine titration

23
Q

Fixed Dose=

A

Give fixed amount of protamine for each unit of heparin that was given

  • Usually 1 to 1.3 mg of protamine per 100 units of heparin
  • Usually based on total amount of heparin given during the case or based on initial heparin loading dose
24
Q

Fixed Dose advantages

A

Simple
Does not rely on ACT
“It’s a really easy protocol to write”

25
Q

Fixed Dose disadvantages

A

Variability of heparin half-life so could give too much or too little

26
Q

Heparin ACT Dose-Response Curve=

A
Plot pre and post heparin ACT
Determine slope of curve
Measure ACT after termination of bypass
Calculate total heparin load
-Protamine dose is usually 1.3 mgs per 100 units of total heparin load
27
Q

Heparin ACT Dose-Response Curve advantages

A

Easy to use

More accurate protamine dose – less protamine given; Decreased blood product requirements

28
Q

Heparin ACT Dose-Response Curve disadvantages

A

You gotta do math…

Relies on ACT (No fixed correlation between ACT and heparin concentrations , i.e. other factors affect ACT)

29
Q

Heparin Concentration method advantages

A

Consistently results in lower protamine dose versus ACT response curve

30
Q

Heparin Concentration method disadvantages

A
  • Takes time to determine
  • Requires estimate of patient plasma volume
  • Not always good correlations between heparin concentrations and clotting times
  • Because of time requirement, protamine dose may not reflect actual heparin concentration when given (heparin continued to be metabolized)
31
Q

Protamine Titration=

A
  • Tubes of various dilutions of a protamine solution
  • Fixed volume of heparinized whole blood added
  • Tube with lowest concentration resulting in the shortest clotting time represents best neutralization of heparin
  • Actual protamine dose calculated-neutralization ratio
32
Q

Protamine Titration advantages

A

Usually give less protamine than fixed dose
Less post operative bleeding
Less exposure to blood products
Absence of heparin rebound

33
Q

Protamine Titration disadvantages

A

Estimation of patient’s blood volume

Variability of heparin and protamine preparations

34
Q

Heparin neutralization complications

A
  1. Heparin-Protamine complex activates the complement cascade via the classical pathway
  2. Allergic reactions
  3. Pulmonary hypertension
  4. Transient systemic hypotension in most patients
35
Q

Adverse Reactions to Protamine
REACTION CLASSIFICATION I
Type I =

A
  • Mild hypotension due to histamine release (Rapid infusion)

- Can be ameliorated by giving protamine intra-arterial

36
Q

Your Nemesis=

A

Histamine

-Basophils/Mast cells

37
Q

Specific Histamine receptors cause (6)-

A
  • Increase sensitivity to pain and itching
  • Dilation of arterioles and precapillary sphincters
  • Increased HR (both direct and reflex effect)
  • Most critters experience bronchoconstriction
  • Increase GI motility
  • Wheals and flares
38
Q

Cromolyn sodium=

A

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

39
Q

Adverse Reactions to Protamine
REACTION CLASSIFICATION I
Type IIa =

A
  • True anaphylaxis- IgE mediated. Anamnestic
  • Decreased SVR, PA, LA, RA pressures +/- bronchospasm
  • ~50% of IDDM patients taking NPH insulin have anti-protamine IgE
40
Q

Adverse Reactions to Protamine
REACTION CLASSIFICATION I
Type IIb =

A
  • Immediate Anaphylactoid- No IgE involvement
  • Mediated by thromboxane
  • leads to pulmonary vasoconstriction & bronchoconstriction
41
Q

Adverse Reactions to Protamine
REACTION CLASSIFICATION I
Type IIc =

A
  • Delayed Anaphylactoid
  • Increased post-0p pulmonary edema
  • Also related to complement activation with histamine/thromboxane/”others” release
42
Q

Adverse Reactions to Protamine
REACTION CLASSIFICATION I
Type III =

A
  • Occurs in 0.6% of adult cardiac surgical patients
  • Catastrophic pulmonary vasoconstriction (IgG/complement-mediated)
  • Noncardiogenic pulmonary edema
  • Intense vasoconstriction seems to be thromboxane-mediated
  • No long-term negative sequelae
43
Q

Adverse Reactions to Protamine
REACTION CLASSIFICATION II
Type A =

A

Pharmacologic histamine release

44
Q

Adverse Reactions to Protamine
REACTION CLASSIFICATION II
Type B =

A

True anaphylaxis (IgE mediated)

45
Q

Adverse Reactions to Protamine
REACTION CLASSIFICATION II
Type C =

A

Anaphylactoid thromboxane release
Pulmonary vasoconstriction
Bronchoconstriction

46
Q

Risk Factors=

A
  1. Fish Allergy (up to 27% of general population)

2. Antibody development (5%) from prior exposure

47
Q

Potential Risk of True Allergic Response-

Prior reaction to protamine risk increase

A

189 fold increase

48
Q

Potential Risk of True Allergic Response-

Allergy to fish risk increase

A

24.5 fold increase

49
Q

Potential Risk of True Allergic Response-

Exposure to NPH insulin risk increase

A

8.2 fold increase

50
Q

Potential Risk of True Allergic Response-

Allergy to any drug risk increase

A

3 fold increase

51
Q

Potential Risk of True Allergic Response-

Prior exposure to protamine risk increase

A

No increase

52
Q

Rate of Administration

A

Studies suggest no faster than 5 mg/minute although 15 mg/minute might be more common

53
Q

Alternatives to protamine= (6)

A
  1. Allow heparin to be metabolized
  2. Platelet concentrates
  3. Hexadimethrine
  4. Heparinase I
  5. Lactoferrin
  6. Heparin-Removal Devices
54
Q

Platelet concentrates=

A
  • Platelet factor 4 (PF4) released from activated platelets combines with and neutralizes protamine
  • Platelet concentrates do not restore coagulation following bypass
55
Q

Hexadimethrine=

A
  • Synthetic polycation – not easy to get in US
  • Problems with renal toxicity
  • Use can avoid true allergic reactions due to protamine
  • Still can produce pulmonary vasoconstriction if given too quickly