title: Ro 44-9883, a new nonpeptide glycoprotein IIb/IIIa antagonist, prevents platelet loss during experimental cardiopulmonary bypass.
abstract: Extensive contact between blood and artificial surfaces causes platelet activation and depletion. The aim of the study was to test the efficacy of Ro 44-9883, a new nonpeptide, reversible, glycoprotein IIb/IIIa antagonist in preventing platelet count drop in dogs undergoing cardiopulmonary bypass during 2 hours. Twenty-two heparinized dogs were divided into three groups, one control group (n = 9) not treated, one group treated with a low dose of Ro 44-9883 (145 micrograms/kg intravenously, n = 6), and one group treated with a high dose of Ro 44-9883 (870 micrograms/kg intravenously, n = 7). In the control group, platelet counts declined to 53% +/- 15% of initial levels at the start of cardiopulmonary bypass and remained lower than 80% of initial levels during follow-up. Platelet count drop was completely prevented in the Ro 44-9883 high-dose group, whereas it was only partially prevented in the low-dose group. Blood loss was similar in the three groups despite the fact that bleeding times were longer in the Ro 44-9883 high-dose group than in the control group. We conclude that Ro 44-9883, together with heparin as a standard anticoagulant, is highly effective in preventing platelet count drop during cardiopulmonary bypass without causing excessive bleeding.
authors.affiliation: Pharma Division, F. Hoffmann-La Roche Ltd, Basel, Switzerland.
authors.forename: J P
authors.initials: JP
authors.lastname: Carteaux
authors.forename: S
authors.initials: S
authors.lastname: Roux
authors.forename: H
authors.initials: H
authors.lastname: Kuhn
authors.forename: T
authors.initials: T
authors.lastname: Tschopp
authors.forename: V
authors.initials: V
authors.lastname: Colombo
authors.forename: P
authors.initials: P
authors.lastname: Hadváry
mesh_terms: D000085:Acetates / Q000494:pharmacology*; D000818:Animals; D001780:Blood Coagulation Tests; D016063:Blood Loss, Surgical / Q000517:prevention & control; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D004285:Dogs; D005260:Female; D005340:Fibrinogen / Q000032:analysis; D006400:Hematocrit; D008297:Male; D008855:Microscopy, Electron, Scanning; D010107:Oxygenators, Membrane; D010974:Platelet Aggregation / Q000187:drug effects*; D010976:Platelet Count / Q000187:drug effects; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors*; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D000085:Acetates; D010980:Platelet Membrane Glycoproteins; D014443:Tyrosine; D005340:Fibrinogen; C084062:lamifiban