Differential effects of citrate versus PPACK anticoagulation on measured platelet inhibition by abciximab, eptifibatide and tirofiban.
BACKGROUND
High levels of glycoprotein (GP) IIb/IIIa receptor inhibition are required to prevent arterial thrombosis following percutaneous coronary intervention. Ex-vivo turbidometric platelet aggregation in citrate anticoagulated blood samples has been the primary method previously utilized to derive dose regimens for administering platelet GP IIb/IIIa inhibitors. Enhanced GP IIb/IIIa binding and inhibition of platelet aggregation for eptifibatide secondary to citrate induced reduction of ionized plasma calcium concentrations has been reported.


RESULTS
We evaluated the differential effects of citrate versus PPACK anticoagulation on turbidometric platelet inhibition in normal volunteers by eptifibatide, tirofiban or abciximab. The decrease in ionized calcium afforded by citrate was associated with enhanced in vitro platelet inhibition for all three GP IIb/IIIa inhibitors, including abciximab. The magnitude of citrate effect was greatest for eptifibatide. Both tirofiban and abciximab have similar citrate calcium chelation associated enhancement of measured platelet inhibition.


CONCLUSIONS
Accurate assessment and comparison of platelet inhibition by GP IIb/IIIa inhibitors may require avoidance of calcium chelating anticoagulants.
Kereiakes
D J
DJ
The Carl and Edyth Lindner Center for Research and Education, 2123 Auburn Avenue, Suite 424, Cincinnati, OH 45219, USA. lindner@fuse.net
Lorenz
T
T
Young
J J
JJ
Kukielka
G
G
Mueller
M N
MN
Nanniazzi-Alaimo
L
L
Phillips
D R
DR
D000077284:Abciximab; D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology*; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000925:Anticoagulants / Q000494:pharmacology; D000991:Antithrombins / Q000494:pharmacology*; D001800:Blood Specimen Collection / Q000379:methods / Q000592:standards; D002118:Calcium / Q000494:pharmacology; D002614:Chelating Agents / Q000494:pharmacology*; D019343:Citric Acid / Q000494:pharmacology*; D004347:Drug Interactions; D016903:Drug Monitoring / Q000379:methods / Q000592:standards; D000077542:Eptifibatide; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D010979:Platelet Function Tests / Q000592:standards; D000077466:Tirofiban; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000494:pharmacology
D000590:Amino Acid Chloromethyl Ketones; D000911:Antibodies, Monoclonal; D000925:Anticoagulants; D000991:Antithrombins; D002614:Chelating Agents; D007140:Immunoglobulin Fab Fragments; D010455:Peptides; D010975:Platelet Aggregation Inhibitors; D019343:Citric Acid; D014443:Tyrosine; D000077466:Tirofiban; C040308:phenylalanyl-prolyl-arginine-chloromethyl ketone; D000077542:Eptifibatide; D002118:Calcium; D000077284:Abciximab