Leukocyte-platelet aggregation, platelet surface P-selectin, and platelet surface glycoprotein IIIa after percutaneous coronary intervention: Effects of dalteparin or unfractionated heparin in combination with abciximab.
BACKGROUND
Plaque disruption with resultant platelet activation and leukocyte-platelet aggregation is a pathophysiologic process common to both acute coronary syndromes and percutaneous coronary interventions. Unfractionated heparin is a standard antithrombotic therapy in patients with both acute coronary syndromes and in those undergoing percutaneous coronary interventions. Low-molecular-weight heparins have been reported to cause less platelet activation than unfractionated heparin.


METHODS
Monocyte-platelet aggregates, neutrophil-platelet aggregates, platelet surface P-selectin, and platelet surface glycoprotein (GP) IIIa were measured serially by whole blood flow cytometry in 40 patients with unstable angina (randomly assigned to either unfractionated heparin 70 U/kg or the low-molecular-weight heparin dalteparin 60 IU/kg) undergoing coronary intervention with planned abciximab administration (in 2, one-half-dose boluses). Assays were performed at baseline, 5 minutes after administration of either type of heparin, 10 minutes after the first bolus of abciximab, 10 minutes after second bolus of abciximab, and 8 to 10 and 16 to 24 hours after administration of either heparin.


RESULTS
No significant differences in clinical outcomes were observed between patients receiving either unfractionated heparin or dalteparin. The number of circulating P-selectin-positive platelets was increased by unfractionated heparin but not dalteparin, and abciximab reversed this increase. The number of circulating P-selectin-positive platelets was reduced below baseline levels in both treatment groups 8 to 10 and 16 to 24 hours after study drug administration. At 8 to 10 and 16 to 24 hours after administration of study drug, platelet degranulation in response to iso-thrombin receptor agonist peptide 1.5 mmol/L was significantly reduced by almost 50% (compared with immediately after study drug administration). Both unfractionated heparin and dalteparin significantly increased the numbers of circulating monocyte-platelet and neutrophil-platelet aggregates, which were subsequently reduced to baseline levels after administration of the second abciximab bolus and to below baseline at both 8 to 10 and 16 to 24 hours in all patients. After both unfractionated heparin and dalteparin administration, platelet surface GP IIIa expression was significantly increased compared with baseline at both 8 to 10 and 16 to 24 hours.


CONCLUSIONS
Dalteparin in combination with abciximab in patients with unstable angina undergoing coronary intervention appears to be safe. Unfractionated heparin, but not dalteparin, degranulates platelets in patients with unstable angina. Both heparins increase the number of circulating monocyte-platelet and neutrophil-platelet aggregates. Abciximab therapy during coronary interventions rapidly reduces the number of degranulated platelets and leukocyte-platelet aggregates.
Furman
M I
MI
Center for Platelet Function Studies and the Division of Cardiovascular Medicine, Departments of Medicine, Pediatrics, and Cell Biology, University of Massachusetts Medical School, Worcester, MA 01655, USA. Furman@platelets.org
Kereiakes
D J
DJ
Krueger
L A
LA
Mueller
M N
MN
Pieper
K
K
Broderick
T M
TM
Schneider
J F
JF
Howard
W L
WL
Fox
M L
ML
Barnard
M R
MR
Frelinger
A L
AL
Michelson
A D
AD
D000077284:Abciximab; D015906:Angioplasty, Balloon, Coronary; D000911:Antibodies, Monoclonal / Q000494:pharmacology* / Q000627:therapeutic use; D015703:Antigens, CD / Q000187:drug effects*; D017073:Atherectomy; D003327:Coronary Disease / Q000188:drug therapy* / Q000601:surgery*; D017985:Dalteparin / Q000494:pharmacology* / Q000627:therapeutic use*; D005343:Fibrinolytic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D006493:Heparin / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000494:pharmacology* / Q000627:therapeutic use; D039661:Integrin beta3; D007962:Leukocytes / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism; D019007:P-Selectin / Q000187:drug effects*; D010974:Platelet Aggregation / Q000187:drug effects*; D010980:Platelet Membrane Glycoproteins / Q000187:drug effects*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D005343:Fibrinolytic Agents; D007140:Immunoglobulin Fab Fragments; D039661:Integrin beta3; D019007:P-Selectin; D010980:Platelet Membrane Glycoproteins; D006493:Heparin; D017985:Dalteparin; D000077284:Abciximab