Anticoagulation on

CPB
By:-SYED AZHAR AHMED
Msc.Perfusion technology
Narayana Hrudayalaya
Topics to Be Covered
• History
• Pharmacology
• Pharmacokinetics
• Dosage
• Heparin Resistance
• HIT
• Heparin Neutralization
History
• Heparin was discovered
accidentally in 1916 by a
medical student Jay McLean.
• Purification of heparin
proceeded in 1920’s.
• First used for transfusion 1924.
The discoverer of heparin Jay McLean
• Another 12 years to make it safe
for IV use.
Pharmacology
• Heparin is a glycosaminoglycan, it is a polysaccharide that
present in mast cells.
• Most heparin preparations can be described unfractionated.
• Which means that the heparin compound isolated from the
animal tissues.
• It contains heparin molecules of various lengths.
• Molecular weight (3000-40,000 Da)
• SOURSE :- Porcine mucosa, Bovine lung.
Pharmacokinetics
• Heparin action peaks 10-20 mins after administration in cardiac
surgical patients.
• But prolongation of ACT by other factors such as hemodilution and
hypothermia.
• Distribution :- Distribution of heparin is virtually confined to the plasma
compartment of the blood stream.
• Elimination & Excretion :- Half life – 126 +- 24 mins with dose of 400U/kg
• Hypothermia delays heparin elimination.
• Primary mechanism for heparin elimination remains uncertain, but
metabolism in the reticuloendothelial system and Renal elimination
both occur.
Dosage during CPB
• Initial dose of 200-400 U/kg.
• Maintenance dose of 50-100 U/kg.(administered any where b/w 30min to 2
hours).

• Priming fluid – 10,000-20,000 U.

1ml =5000U 1ml =1000U

Heparin resistance
• Need for higher than normal heparin dose to induce sufficient
anticoagulation for the safe conduct of CPB.
• Clinical situations inducing heparin resistance have
❖ Familial AT III deficiency.
❖ On going heparin therapy.
❖ Extreme thrombocytosis.(platelet count >7,00,000)
❖ Septicemia.
❖ Hyper eosinophilic syndrome.
Alternatives to Heparin
• Clinical situations that might call for avoidance of heparin include
❖ Protamine allergy,

❖ HIT ,

❖ Heparin allergy.

• Alternatives
❖ LMWH,

❖ Hirudin,

❖ Bivalirudin, (1mg/kg Bolus followed by 2.5mg/kg/hr as infusion)

❖ Argatroban, ( 0.1-0.2mg/kg Bolus followed by 5-10μg/kg/min infusion)

Heparin induced thrombocytopenia
• Develops in 5-28% of patients receiving heparin.

• Two types:-
➢ Type I HIT :- Mild decrease in platelet count.

➢ Type II HIT :- More severe, most often occurs after more than 5 days of heparin administration.

• Management of HIT
➢ Discontinuation of heparin for 4-8 weeks,

➢ Changing tissue source of heparin,

➢ LMWH can be used,

➢ Use of heparin substitutes like Bivalirudin etc.

Heparin neutralization
Protamine , a polycationic protein derived from salmon sperm.
• It is strongly alkaline.
• Heparin , a polyanionic, binds ionically to protamine to produce
a stable precipitate.
• Protamine contains two active sites, one that neutralizes heparin
and another that exerts a mild anticoagulant effect
independently of heparin.
Fixed protamine dose regimen
• Fixed dose ratio of protamine to heparin.
• 1.0 to 1.3 mg of protamine for each 100U of heparin.
Alternatives:-
• Platelet factor 4
• Protamine variants
• Heparinase, derived from the bacterium (Flavobacterium
heparinum).
• Heparin removal devices.
Protamine reactions
• Hemodynamic compromise following protamine administration
during cardiac surgery is well known & documented.
• Characterized by :-
➢ Increase in PA pressure & CVP.

➢ Decrease in left atrial & systemic arterial pressure.

• Possible causes are :-

➢ Pharmacological histamine release

➢ Anaphylactoid reaction

➢ True anaphylaxis mediated by specific antiprotamine Ig.

 Protamine reactions
TYPE HORROW MOORMAN, ZAPOL,
LOWENSTEIN
I. Hypotension resulting from Pharmacological histamine
rapid administration release

IIa. Anaphylactic reactions True anaphylaxis

(IgE-mediated)
IIb. immediate anaphylactoid
reactions

IIc. Delayed anaphylactoid Anaphylactoid reactions

reactions

III. Catastrophic pulmonary Pulmonary vasoconstriction

vasoconstriction (IgG/complement-
mediated)
Noncardiogenic pulmonary
edema.