Increased anticoagulation during cardiopulmonary bypass by aprotinin.
In this prospective study, the effect of the antiproteinase aprotinin on anticoagulation during cardiopulmonary bypass was compared with placebo treatment in a randomized double-blind fashion. The kallikrein-inhibiting capacity was significantly increased in aprotinin-treated patients and decreased in the control patients. The intrinsic clotting system was also inhibited by aprotinin. We demonstrated during cardiopulmonary bypass and in vitro a significantly prolonged activated clotting time and a remarkable prolongation of the activated partial thromboplastin time by aprotinin at low heparin concentrations, whereas the antithrombin III consumption was significantly reduced. Aprotinin synergistically enhanced the anticoagulation by heparin, which allowed reduced heparinization. This is of clinical importance for use in both heparin-resistant and heparin-sensitive patients undergoing cardiopulmonary bypass and may also have advantages for routine use during bypass to reduce the adverse effects of heparin-protamine complexes.
Thoraxcentre, University Hospital Groningen, The Netherlands.
A A
AA
de Smet
M C
MC
Joen
W
W
van Oeveren
K J
KJ
Roozendaal
M P
MP
Harder
L
L
Eijsman
C R
CR
Wildevuur
D000990:Antithrombin III / Q000187:drug effects; D007611:Aprotinin / Q000627:therapeutic use*; D001777:Blood Coagulation / Q000187:drug effects*; D002315:Cardiopulmonary Bypass / Q000379:methods*; D001026:Coronary Artery Bypass; D004311:Double-Blind Method; D005344:Fibrinopeptide A / Q000378:metabolism; D006493:Heparin / Q000008:administration & dosage; D006801:Humans; D007610:Kallikreins / Q000037:antagonists & inhibitors; D010314:Partial Thromboplastin Time; D010976:Platelet Count / Q000187:drug effects; D011446:Prospective Studies; D013931:Thromboxanes / Q000097:blood; D014914:Whole Blood Coagulation Time
D013931:Thromboxanes; D005344:Fibrinopeptide A; D000990:Antithrombin III; D006493:Heparin; D007611:Aprotinin; D007610:Kallikreins