title: Aprotinin inhibits plasmin-induced platelet activation during cardiopulmonary bypass.
abstract: BACKGROUND
  In the past few years, aprotinin has been used in cardiac surgery with impressive results of reducing blood loss, but several adverse effects of aprotinin also have been reported. One of the most likely mechanisms is the inhibition of plasmin by aprotinin, although this indirect effect has not been reproduced in all experimental studies.
  
  
  RESULTS
  We evaluated the platelet function and fibrinolytic activity during human cardiac surgery, with or without aprotinin. During cardiopulmonary bypass (CPB) in humans without aprotinin (n=16), decrease of platelet aggregation induced by thrombin, increase of alpha-granule secretion of platelet and microparticle formation, and increase of plasmin/alpha2-antiplasmin complex (PIC) were observed. In contrast, low-dose aprotinin (1.0 x 10(6) KIU), which was administered only into the priming fluid of extracorporeal circuits (n=10), maintained platelet aggregation induced by thrombin and reduced alpha-granule secretion and microparticle formation of platelets during CPB. In vitro, plasmin (0.8 CU/mL) released alpha-granules of washed platelets, and this activation was completely inhibited by aprotinin (10 KIU/mL).
  
  
  CONCLUSIONS
  Aprotinin has indirect effects to inhibit platelet activation, and this may partly explain the reduction of blood loss during cardiac surgery. To prevent the adverse effects, a single and minimal use of aprotinin is important. The results of in vivo and in vitro studies suggest that platelet preservation was demonstrated by the lower concentration of aprotinin (1.0 x 10(6) KIU per patient or 10 KIU/mL) compared with the concentration that inhibits plasma fibrinolysis.
authors.affiliation: Division of Cardiovascular Surgery, Institute of Clinical Medicine, University of Tsukuba, Ibaraki, Japan.
authors.forename: O
authors.initials: O
authors.lastname: Shigeta
authors.forename: H
authors.initials: H
authors.lastname: Kojima
authors.forename: T
authors.initials: T
authors.lastname: Jikuya
authors.forename: Y
authors.initials: Y
authors.lastname: Terada
authors.forename: N
authors.initials: N
authors.lastname: Atsumi
authors.forename: Y
authors.initials: Y
authors.lastname: Sakakibara
authors.forename: T
authors.initials: T
authors.lastname: Nagasawa
authors.forename: T
authors.initials: T
authors.lastname: Mitsui
mesh_terms: D000368:Aged; D007611:Aprotinin / Q000008:administration & dosage*; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D002478:Cells, Cultured; D005260:Female; D005341:Fibrinolysin / Q000494:pharmacology*; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D005434:Flow Cytometry; D006490:Hemostatics / Q000008:administration & dosage*; D006801:Humans; D007431:Intraoperative Complications / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D015539:Platelet Activation / Q000187:drug effects*
chemical_list: D005343:Fibrinolytic Agents; D006490:Hemostatics; D007611:Aprotinin; D005341:Fibrinolysin