title: Aprotinin counteracts heparin-induced inhibition of platelet contractile force.
abstract: BACKGROUND
  Aprotinin interferes with heparin binding to platelets and decreases blood loss during cardiopulmonary bypass (CPB). Heparin abolishes platelet force during CPB, and the extent of platelet force recovery after protamine administration appears to correlate with blood loss. This study assessed the effect of aprotinin on heparin suppression of platelet force.
  
  
  METHODS
  Platelet force was measured using the Hemodyne Hemostasis Analyzer. Clots were formed from platelet-rich plasma (PRP) by the addition of batroxobin and 10 mM CaCl(2). Clotting conditions included pH 7.4, ionic strength 0.15 M, fibrinogen level 1 mg/ml and 75,000 platelets/microl.
  
  
  RESULTS
  After 1200 s of clotting, force was reduced from 7110+/-1190 to 450+/-450 dyn by 0.2 U/ml of heparin. Platelet force in aprotinin [20 microg/ml (140 KIU/ml)] containing PRP was not suppressed by heparin addition (7480+/-2410 dyn). Aprotinin [40 microg/ml (280 KIU/ml)] addition to previously heparinized plasma counteracted heparin force suppression. Aprotinin (40 microg/ml) increased platelet force from 5630 to 11,138+/-562 in PRP devoid of heparin. Aprotinin did not affect thrombin activity, fibrin structure, platelet aggregation or secretion.
  
  
  CONCLUSIONS
  Aprotinin counteracts heparin suppression of platelet force and enhances platelet force in the absence of heparin. Aprotinin-heparin-platelet interactions may help explain aprotinin's ability to reduce blood loss during CPB.
authors.affiliation: Department of Internal Medicine, Medical College of Virginia, Virginia Commonwealth University, Richmond, 23298, USA. mcarr@hsc.vcu.edu
authors.forename: Marcus E
authors.initials: ME
authors.lastname: Carr
authors.forename: Sheryl L
authors.initials: SL
authors.lastname: Carr
authors.forename: Veronica
authors.initials: V
authors.lastname: Roa
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: McCardell
authors.forename: Philip E
authors.initials: PE
authors.lastname: Greilich
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D007611:Aprotinin / Q000494:pharmacology*; D016063:Blood Loss, Surgical / Q000517:prevention & control; D001792:Blood Platelets / Q000187:drug effects* / Q000502:physiology*; D002315:Cardiopulmonary Bypass; D004347:Drug Interactions; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D010974:Platelet Aggregation / Q000187:drug effects; D010979:Platelet Function Tests / Q000295:instrumentation / Q000379:methods
chemical_list: D000255:Adenosine Triphosphate; D006493:Heparin; D007611:Aprotinin