Pharmacological haemostatic agents in cardiothoracic surgery

By Alex Yartsev - Jul 12, 2015

This brief summary is a consequence of the CICM examiner's interest in DDAVP, aprotinin and tranexamic acid. Question 4 from the first paper of 2001 asks the candidate to compare their pharmacodynamic properties. There was nothing particularly "cardiothoracic" about the discussion of the college answer in this question, and it has been relegated into the haematology section.

As with many such questions, the answer looks better when tabulated.

A Comparison of Pharmacological Haemostatic Agents
Properties	DDAVP	Aprotinin	Tranexamic acid
Class	Vasopressin analogue	Non specific serine protease inhibitor	Lysine analogue
Mechanism	Induces release of the contents of endothelial cell- associated Weibral-Palade bodies, including von Willebrand factor.	Inhibitor of trypsin, plasmin, kalikrein, contact phase of coagulation: this inhibits fibrinolysis, coagulation and inflammation	Potent, specific inhibitor of fibrinolysis (a tissue plasminogen activator inhibitor)
Dose	0.3μg/kg	2 million KIU IV over 20-30min Prime pump with 2 million KIU IV Then, continuous intraoperative infusion of 0.5million KIU/hour	30 mg/kg bolus followed by 16 mg/kg/hr infusion seems to be the favoured dose.
Advantages	May decrease transfusion needs perioperatively May antagonise persistent antiplatelet agent effects	May prevent clotting activation, factor consumption and platelet dysfunction, leading to reduced blood loss.	Reduces transfusion needs Does not increase the risk of MI
Disadvantages	May lead to water retention and vasoconstriction A small effect on transfusion rate but a two fold increase in rate of perioperative MI.	Discontinued! No longer available. Slight increase in the rate of MI	Does not improve outcome
Side effects	Fluid retention Increased afterload Hyponatremia	Sensitization and hypersensitivity reactions, including anaphylaxis	Myopathy Hypotension Intravascular thrombosis.

A comparative review of all three substances is available; in summary its findings are as follows:

All three result in a significant decrease in blood loss
All three have no effect whatsoever on mortality
Aprotinin and tranexamic acid are slightly better than DDAVP in preventing re-sternotomy
Aprotinin was slightly better as a haemostatic agent in terms of trasnfusion requirements
Tranexamic acid is the only one of them which is not associated with an increased risk of MI.

References

Sigaut, Stéphanie, et al. "Comparison of two doses of tranexamic acid in adults undergoing cardiac surgery with cardiopulmonary bypass." Anesthesiology120.3 (2014): 590-600.

Laupacis, Andreas, and Dean Fergusson. "Drugs to minimize perioperative blood loss in cardiac surgery: meta-analyses using perioperative blood transfusion as the outcome." Anesthesia & Analgesia 85.6 (1997): 1258-1267.

Levi, Marcel, et al. "Pharmacological strategies to decrease excessive blood loss in cardiac surgery: a meta-analysis of clinically relevant endpoints." The Lancet 354.9194 (1999): 1940-1947.

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