title: The effect of two different doses of aprotinin on hemostasis in cardiopulmonary bypass surgery: similar transfusion requirements and blood loss.
abstract: OBJECTIVE
  Various dosages of aprotinin have proven to be effective in reducing blood loss and allogeneic transfusion requirements in cardiopulmonary bypass surgery, despite the controversy surrounding the precise hemostatic mechanisms of this drug. The aim of our prospective, randomized, double-blind study was to assess differences in blood loss and transfusion requirements and the effect of two dosages of aprotinin on hemostatic activation.
  
  
  METHODS
  Patients undergoing coronary artery bypass grafting received high-dose aprotinin (n=28), pump-prime-only (PPO) aprotinin (n=28), or placebo (n=28).
  
  
  RESULTS
  The high-dose and the PPO groups had a significantly lower blood loss (985 mL [95%CI 845-1,102] and 1,255 mL, [95% CI 1,025-1,406], respectively) than the placebo group (1,416 mL, 95%CI 1,248-1,612]. Transfusion requirements were lower in the aprotinin-treated groups than in the patients receiving placebo (21 units and 15 units in the high and low-dose groups vs 59 units in placebo group). As far as concerns parameters of thrombin generation, the aprotinin groups showed a significant reduction of F1+2 prothrombin fragment but not of thrombin-antithrombin complexes. There were higher levels of natural anticoagulants, i.e. antithrombin, protein C and protein S, in the high-dose aprotinin group. As regards fibrinolysis parameters, D-dimer was lower in the aprotinin groups, and the levels of alpha2-antiplasmin and plasmin-alpha2-antiplasmin complexes were raised. In summary, both dosages of aprotinin were equally effective in reducing blood loss and transfusion requirements. There was a lower activation of coagulation and fibrinolysis in cardiopulmonary bypass patients treated with aprotinin: the levels of natural anticoagulants were less decreased in the high-dose group. No differences in thrombotic complications were observed between aprotinin groups.
  
  
  CONCLUSIONS
  Our study shows that both dosages of aprotinin are safe and effective in reducing transfusion requirements. Considering the difference in cost of using a low-dose or high-dose schedule, the former should be recommended for patients undergoing cardiopulmonary bypass surgery.
authors: Thrombosis and Haemostasis Unit, Haematology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
authors: A
authors: A
authors: Santamaría
authors: J
authors: J
authors: Mateo
authors: A
authors: A
authors: Oliver
authors: H
authors: H
authors: Litvan
authors: J
authors: J
authors: Murillo
authors: J C
authors: JC
authors: Souto
authors: J
authors: J
authors: Fontcuberta
mesh_terms: D000328:Adult; D000368:Aged; D007611:Aprotinin / Q000008:administration & dosage* / Q000009:adverse effects; D016063:Blood Loss, Surgical / Q000517:prevention & control; D001803:Blood Transfusion; D002315:Cardiopulmonary Bypass / Q000009:adverse effects / Q000379:methods; D004311:Double-Blind Method; D005260:Female; D006487:Hemostasis / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies
chemical_list: D007611:Aprotinin