Ro 44-9883, a new nonpeptide glycoprotein IIb/IIIa antagonist, prevents platelet loss during experimental cardiopulmonary bypass.
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.
Carteaux
J P
JP
Pharma Division, F. Hoffmann-La Roche Ltd, Basel, Switzerland.
Roux
S
S
Kuhn
H
H
Tschopp
T
T
Colombo
V
V
Hadváry
P
P
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
D000085:Acetates; D010980:Platelet Membrane Glycoproteins; D014443:Tyrosine; D005340:Fibrinogen; C084062:lamifiban