1) Hemodilution of Antithrombin III as well as the continuous infusion of heparin preoperatively may do what to your patient?

2) What other drug may interact with heparin giving you grief?

1) Reduce the responsiveness to heparin. 

2) Nitroglycerin-  mechanism is unclear however well documented.

Fill in the blanks:( in regards to Heparin)

1) Bleeding may increase in patients who are taking other ______(a)________ such as _____(b)_____ and _____(c)______.

A: anticoagulants

B: NSAIDS (including ASA)

C: Warfarin

If I am a drunkard and have poor nutrition what is my concern with heparin?

Fewer plasma proteins (including coag factors) d/t poor nutrition and vitamin K intake. 

This makes drunks susceptible to spontaneous bleeding

Heparin is made from Pig Scrims

(okay no it isn't)

BUT

It is made from animal tissue- so what?

Allergic rxns can occur and exhibit as:

Fever,

Itching,

rash

or EVEN CARDIOPULMONARY changes (hypotension and bronchospasm)

Barash is a tool.

Admittedly a smart tool-->  he believes that heparin has a direct action on vascular smooth  musculature-

1) What is this action? 

2) How will it present?

3) What is another theory for this action?

4) Who really gives a shit?   

1) Reduction in SVR and PVR

2) Transient hypotension

3) Gayle was taught that the hypotension was d/t a decreased ionized calcium in the vascular beds. 

4) The preceptor asking you this question in the Heart room bitches!

1) 2/3rds of protamine is this:

2) What is it made from?

3) How does it work to produce its magically anticoagulant effect? 

1) Arginine- a very alkaline amino acid

2) Salmon Sperm

3) Positive charged protamine binds to the negative charged heparin forming a stable complex that has no coagulant effects.

1) How is the protamine/heparin complex cleared and  how fast does it get cleared? 

1) How does one dose protamine to reverse heparin?

1 mg for every 100 units of predicted heparin

(see slide 22 for Gayle's example)

When one reverses heparin with protamine-

heparin rebound can occur (reheparinization)

WHY?

1) How fast can I push protamine?

2) Some Authors that are tools (as previously mentioned) recommend a test dose of protamine- what is the recommended test dose?

1) SLOWLY  5 mg/ min

2) 10 mg test dose is Barash Recommended.

1) Histamine release

2) Hypotension

3) Tachycardia

4) Facial Flushing

1) Protamine can cause pulmonary vasoconstriction, pulmonary HTN, and bronchoconstriction (although rare).  What is the mechanism? 

2) What is the  treatment should it occur?

1) d/t release of thrombaxane A2 and serotonin resulting in pulmonary vasoconstriction, pulmonary HTN, and bronchoconstriction

2) Treatment is aimed at blocking thrombaxane A2 by administering a cyclooxygenase inhibitor like ASA or indomethacin.

It is the one time your patient would not mind being COX blocked.

Allergic RXNS to protamine can be anaphylactic (IgE mediated-d/t previous exposure)  or anaphylactoid (Non- IgE mediated-no previous exposure):

So what increases the risk of an allergic rxn to protamine?

1) NPH, protamine Zinc insulin

2) Allergies to fish

3) Vasectomy or infertile males (antisperm antibodies)

1) Pretreat with histamine receptor (H1 & H2) antagonists and steroids.  Then give a test dose to see what happens.

2) Allow the spontaneous metabolism of heparin without reversal

3) Try an alternative reversal:

a) Hexadimethrine

b) Platelet factor 4

          -Naturally occurring polypeptide (fewer allrgic                    rxns)

          -Binds to heparin

          -Has been used post CPB

c) Heparinase

          - heparin degrading enzyme

          -tested post CPB

d) Methylene Blue

e) Vancomycin

          -

Fill in the  blanks: (regarding synthetic alternatives to Heparin)

___1___ is derived from leeches.  ___2___ is a synthetic based peptide based on ____1___.  Since they bind directly to ____3____ they do not rely on the presence of antithrombin III.  They do NOT produce _____4_____ and have been used successfully in patients with HITT syndrome.

1) Hirudin

2) Hirulog

3) Thrombin

4) Thrombocytopenia

True or false: (regarding synthetic alternatives to heparin)

1) Hirudin is excreted renally while Hirulog is not.

2) Both Hirudin and Hirulog have short 1/2 lives

3) Hirudin and Hirulog both can be reversed with protamine or platelet factor 4.

4) Hirudin and Hirulog have been used when heparin resistance is present and have been successfully used with cardio-pulmonary bypass. 

5) Both Hirudin and Hirulog affect the APTT and ACT.

1) False.  Both are excreted renally

2) True

3) Nope.  They can't be reversed with these

4) True

5) True

1) Argatroban, a synthetic alternative to heparin, binds where? 

2) Approved for use in what type of patients?

1) Thrombin- but at a different site than hirudin or hirulog. 

2) Pts with a history of HITT and use in CBP circuitry.

1) Do ACT levels and aPTT levels respond to Argatroban?

2) How is argatroban reversed?

1) Yes. They do respond.  (I assume they go up)

2) No reversal is known.  However- the elmination 1/2 life is short (50 min)