Integrilin prevents prolonged bleeding times after cardiopulmonary bypass.
BACKGROUND
Cardiopulmonary bypass reduces platelet number and function, increases postoperative bleeding time, and is the major, unsolved cause of nonsurgical bleeding after open heart operations. Temporary inhibition of platelet function during cardiopulmonary bypass (platelet anesthesia) protects platelets and reduces postoperative bleeding time and bleeding.


METHODS
Integrilin, a short-acting, reversible platelet glycoprotein IIb/IIIa inhibitor was studied in 28 baboons that had 60 minutes of normothermic cardiopulmonary bypass using peripheral cannulas. A control group, two groups that received different doses of Integrilin, and a group that received a combination of Integrilin and low-dose Iloprost were studied. Blood samples for platelet count, aggregation to adenosine diphosphate, beta-thromboglobulin, prothrombin fragment F1.2, thrombin-antithrombin complex, and fibrinopeptide A were obtained at seven time points. Template bleeding times were measured before and at five intervals after cardiopulmonary bypass.


RESULTS
Both doses of Integrilin and the combination of Integrilin and Iloprost significantly protected platelet number, inhibited the response to adenosine diphosphate, and reduced postoperative bleeding times, but they did not reduce beta-thromboglobulin release except in the high-dose Integrilin group. Thrombin formation and activity were qualitatively, but not significantly, reduced in all treatment groups. Bleeding times were not significantly different from baseline at the time protamine was given in the combination group and 60 minutes after protamine administration in all treatment groups.


CONCLUSIONS
Integrilin alone or in combination with Iloprost significantly reduces platelet activation during cardiopulmonary bypass and produces normal or near-normal bleeding times at the time protamine is given.
Suzuki
Y
Y
Department of Surgery, University of Pennsylvania School of Medicine, USA.
Hillyer
P
P
Miyamoto
S
S
Niewiarowski
S
S
Sun
L
L
Rao
A K
AK
Hollenbach
S
S
Edmunds
L H
LH
D000818:Animals; D001760:Bleeding Time; D002315:Cardiopulmonary Bypass; D000077542:Eptifibatide; D005344:Fibrinopeptide A / Q000032:analysis; D016285:Iloprost / Q000008:administration & dosage; D010215:Papio; D010446:Peptide Fragments / Q000032:analysis; D010455:Peptides / Q000008:administration & dosage / Q000627:therapeutic use*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D011479:Protamines / Q000008:administration & dosage; D011516:Prothrombin / Q000032:analysis; D001620:beta-Thromboglobulin / Q000032:analysis
D010446:Peptide Fragments; D010455:Peptides; D010975:Platelet Aggregation Inhibitors; D011479:Protamines; D001620:beta-Thromboglobulin; C045879:prothrombin fragment 1.2; D005344:Fibrinopeptide A; D011516:Prothrombin; D016285:Iloprost; D000077542:Eptifibatide