Is platelet adhesion assay able to quantify drug-induced platelet dysfunction?
The platelet adhesion assay (PADA) is an innovative method for the detection of both normal, pathologically increased or decreased platelet adhesiveness. Adhesion is the first important phase of platelet activation, followed by shape change and aggregation. Adhesion is triggered by glycoproteins (GP) on the platelet surface, mainly by GPIIb/IIIa, and to a lesser extent also by GPIb/V/IX. Since fibrinogen serves as adhesive protein for GPIIb/IIIa receptors, and since the PADA uses polymer particles that become coated with fibrinogen, the PADA is able to monitor GPIIb/IIIa receptor antagonists and to detect overdosing, potentially leading to bleeding complications. Ex vivo, citrated whole blood from healthy volunteers and patients was spiked with increasing GPIIb/IIIa inhibitor concentrations and PADA was measured. Comparing these results with GPIIb/IIIa receptor occupancy, determined by FACS, a basic consistency of the data was shown. Via intracellular signaling, the adenosine diphosphate (ADP) receptor mechanism is closely involved in the activation of GPIIb/IIIa receptors so that also ADP receptor antagonists of the thienopyridine type, especially clopidogrel, can be quantitatively determined by the PADA. In patients under clopidogrel therapy, the therapeutic effect was monitored and also individual dose adjustments were realized. Furthermore, patients having partial or full clopidogrel resistance were identified. Overdoses can be detected as well.
Schumann
Alrun
A
HaemoSys GmbH, Jena, Germany. goetz.nowak@med.uni-jena.de
Bucha
Elke
E
Nowak
Götz
G
D000077284:Abciximab; D000368:Aged; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001791:Blood Platelet Disorders / Q000139:chemically induced* / Q000175:diagnosis*; D001792:Blood Platelets / Q000502:physiology; D002469:Cell Separation; D000077144:Clopidogrel; D004305:Dose-Response Relationship, Drug; D000077542:Eptifibatide; D005260:Female; D005340:Fibrinogen / Q000737:chemistry; D005434:Flow Cytometry; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000494:pharmacology; D010973:Platelet Adhesiveness; D010974:Platelet Aggregation; D010979:Platelet Function Tests / Q000379:methods*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors; D011108:Polymers / Q000737:chemistry; D011725:Pyridines / Q000494:pharmacology; D013988:Ticlopidine / Q000031:analogs & derivatives / Q000494:pharmacology; D000077466:Tirofiban; D014443:Tyrosine / Q000031:analogs & derivatives / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D010455:Peptides; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D011108:Polymers; D011725:Pyridines; C446540:thienopyridine; D014443:Tyrosine; D005340:Fibrinogen; D000077144:Clopidogrel; D000077466:Tirofiban; D000077542:Eptifibatide; D013988:Ticlopidine; D000077284:Abciximab