Platelet CD62 expression and PDGFAB secretion in patients undergoing PTCA and treatment with abciximab.
OBJECTIVE
To investigate a correlation of the platelet activation marker CD62 and secretion of the growth factor PDGF from platelets in coronary patients under therapy with the GPIIb/IIIa-inhibitor abciximab.


METHODS
Flow cytometric assessment of fibrinogen binding (GPIIb/IIIa-binding site) and CD62 expression, as well as PDGF release of human platelets (immunoassay) and platelet aggregation with 20 microM ADP and 2 microg ml(-1) collagen were evaluated in nine patients with stable coronary artery disease. Patients were undergoing elective balloon angioplasty and were treated with aspirin (100 mg day(-1)), heparin (ACT < 220 s) and abciximab (bolus and infusion over 12 h). Blood samples were obtained before initiation of abciximab therapy (under aspirin and heparin) (I), 3 h after angioplasty under abciximab (II) and 12 h after termination of abciximab infusion (III).


RESULTS
Compared with sample I before abciximab therapy, fibrinogen binding was reduced to 37% (+/- 34 s.d., P < 0.05) (II) and 55% (+/- 40 s.d., P < 0.05) (III). Reduced fibrinogen binding also led to a significant reduction of the aggregation response to ADP (down to 37% +/- 20) and collagen (down to 0%). Mean fluorescence intensity of CD62-expression was 78 units (+/- 20 s.d.) (I), 72 units (+/- 14 s.d.) (II) and 64 units (+/- 12 s.d., P < 0.05) (III). PDGF release from isolated, washed platelets was 99 (+/- 33 s.d.) ng/10(9) platelets at (I), 82 (+/- 31 s.d.) ng/10(9) platelets and 96 (+/- 30 s.d.) ng/10(9) platelets.


CONCLUSIONS
The results indicate that despite a strong reduction of GPIIb/IIIa-binding and platelet aggregation, CD62 as a marker of platelet secretion and the secretion product PDGF were only slightly reduced under abciximab treatment. No direct correlation between CD62 expression and PDGF release could be demonstrated.
Graff
J
J
Institute of Clinical Pharmacology, Medical School of the J.W. Goethe University, Frankfurt am Main, Germany. graff@em.uni-frankfurt.de
Andries
D
D
Elsner
M
M
Westrup
D
D
Bassus
S
S
Franz
N
N
Klinkhardt
U
U
Harder
S
S
D000077284:Abciximab; D015906:Angioplasty, Balloon, Coronary / Q000379:methods*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D001792:Blood Platelets / Q000378:metabolism*; D003327:Coronary Disease / Q000097:blood* / Q000188:drug therapy; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000008:administration & dosage / Q000627:therapeutic use*; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D019007:P-Selectin / Q000097:blood* / Q000276:immunology; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000097:blood / Q000494:pharmacology; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D013997:Time Factors
D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D019007:P-Selectin; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D010982:Platelet-Derived Growth Factor; D000077284:Abciximab