Flow cytometric monitoring of glycoprotein IIb/IIIa blockade and platelet function in patients with acute myocardial infarction receiving reteplase, abciximab, and ticlopidine: continuous platelet inhibition by the combination of abciximab and ticlopidine.
BACKGROUND
Improvement of thrombolysis may be achieved by concomitant strong platelet inhibition. To monitor platelet function in patients with myocardial infarction (n=46) who were treated with the fibrinolytic agent reteplase, the glycoprotein (GP) IIb/IIIa blocker abciximab, and the ADP receptor antagonist ticlopidine, we developed a flow cytometric assay.


RESULTS
Binding of abciximab to platelets was directly monitored as the percentage of platelets stained by a goat anti-mouse antibody. Blood drawn 10 minutes and 2 hours after the start of therapy with reteplase and abciximab and during the 12-hour infusion of abciximab demonstrated a maximal blockade of GP IIb/IIIa (10 minutes, 86.2+/-10.3%; 12 hours, 85.8+/-7.1%). Starting at 24 hours, abciximab binding gradually decreased (24 hours, 74.6+/-16.2%; 48 hours, 66.8+/-14.9%; 72 hours, 60.5+/-16.7%; 96 hours, 49.4+/-17.8%; 120 hours, 35.8+/-16. 4%; and 144 hours, 29.9+/-15.3%). Binding of a chicken anti-fibrinogen antibody to platelets, indicating the level of functional blockade of GP IIb/IIIa, was inversely correlated with the binding of abciximab (r=-0.72, P:<0.0001). In blood drawn at 10 minutes, platelet aggregation was maximally inhibited but recovered within 48 hours even if the majority of GP IIb/IIIa receptors were still blocked by abciximab. Reteplase did not influence abciximab binding and did not activate platelets, as measured by P-selectin expression, fibrinogen binding, and platelet aggregation. Platelet inhibition that was achieved during the first 24 hours by abciximab was directly maintained by additional treatment with ticlopidine.


CONCLUSIONS
Flow cytometric monitoring of platelet function allows differentiation of the effects of reteplase, abciximab, and ticlopidine. The combination of abciximab and ticlopidine is an attractive therapeutic strategy that provides a fast and continuous platelet inhibition.
Peter
K
K
Internal Medicine III, University of Freiburg, Freiburg, Germany. peter@med1.ukl.uni-freiburg.de
Kohler
B
B
Straub
A
A
Ruef
J
J
Moser
M
M
Nordt
T
T
Olschewski
M
M
Ohman
M E
ME
Kübler
W
W
Bode
C
C
D000077284:Abciximab; D000368:Aged; D000911:Antibodies, Monoclonal / Q000097:blood / Q000627:therapeutic use*; D001792:Blood Platelets / Q000187:drug effects* / Q000502:physiology; D005260:Female; D005343:Fibrinolytic Agents / Q000097:blood / Q000627:therapeutic use*; D005434:Flow Cytometry; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000097:blood / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood* / Q000188:drug therapy*; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000097:blood / Q000627:therapeutic use*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000187:drug effects*; D011994:Recombinant Proteins / Q000097:blood / Q000627:therapeutic use*; D013988:Ticlopidine / Q000097:blood / Q000627:therapeutic use*; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000097:blood / Q000627:therapeutic use*
D000911:Antibodies, Monoclonal; D005343:Fibrinolytic Agents; D007140:Immunoglobulin Fab Fragments; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D011994:Recombinant Proteins; C087896:reteplase; D010959:Tissue Plasminogen Activator; D013988:Ticlopidine; D000077284:Abciximab