Pharmacological haemostatic agents in cardiothoracic surgery

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
  • Vasopressin analogue
  • Non specific serine protease inhibitor
  • Lysine analogue
  • 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)
  • 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.

  • 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.
  • 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.