PlA polymorphism and platelet reactivity following clopidogrel loading dose in patients undergoing coronary stent implantation.
The PlA polymorphism (Leu33Pro) of the platelet glycoprotein (GP) IIIa gene has been suggested to play an important role in coronary thrombosis. In vitro studies have shown differences for this polymorphism in platelet sensitivity towards antiplatelet drugs (aspirin and abciximab), suggesting a pharmacogenetic modulation. The aim of the study was to assess the modulatory effect of the PlA polymorphism on clopidogrel-induced antiplatelet effects in 38 patients undergoing coronary stent implantation receiving a 300 mg clopidogrel loading-dose. Platelet reactivity was assessed as GPIIb/IIIa activation and P-selectin expression in platelets stimulated with 2 micromol/l adenosine diphosphate using whole blood flow cytometry. The distribution of the homozygous PlA1/A1 and heterozygous PlA1/A2 genotypes were 74 and 26%, respectively. PlA2 carriers had a higher degree of GPIIb/IIIa activation (P = 0.05) and P-selectin expression (P = 0.02) during the overall study time course and a lower antiplatelet effect to a 300 mg clopidogrel loading-dose up to 24 h following intervention (P < 0.05). In conclusion, the Pl polymorphism of the GPIIIa gene modulates platelet reactivity towards clopidogrel front loading in patients undergoing coronary stenting. This suggests the need for individualized antithrombotic regimens to optimally inhibit platelet reactivity.
Angiolillo
Dominick J
DJ
Cardiovascular Institute, San Carlos University Hospital, Madrid, Spain. dominickjangiolillo@hotmail.com
Fernandez-Ortiz
Antonio
A
Bernardo
Esther
E
Alfonso
Fernando
F
Sabaté
Manel
M
Fernández
Cristina
C
Stranieri
Chiara
C
Trabetti
Elisabetta
E
Pignatti
Pier Franco
PF
Macaya
Carlos
C
D000077284:Abciximab; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000368:Aged; D019943:Amino Acid Substitution / Q000235:genetics; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D001241:Aspirin / Q000008:administration & dosage; D001792:Blood Platelets / Q000378:metabolism / Q000473:pathology; D000077144:Clopidogrel; D003328:Coronary Thrombosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000008:administration & dosage; D039661:Integrin beta3 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D019007:P-Selectin / Q000096:biosynthesis; D015539:Platelet Activation / Q000187:drug effects / Q000235:genetics*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000096:biosynthesis; D011110:Polymorphism, Genetic; D015607:Stents; D013988:Ticlopidine / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D039661:Integrin beta3; D019007:P-Selectin; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D000244:Adenosine Diphosphate; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin; D000077284:Abciximab