title: Reference curves for aggregation and ATP secretion to aid diagnose of platelet-based bleeding disorders: effect of inhibition of ADP and thromboxane A(2) pathways.
abstract: Platelet aggregation is widely used in clinical laboratories to evaluate patients with bleeding disorders of suspected platelet aetiology. Simultaneous monitoring of ATP release as a measure of dense granule secretion provides additional information to aid diagnosis. There is, however, no standard way of performing or interpreting these tests. The present study has evaluated aggregation and ATP secretion to eight platelet agonists in healthy donors and has evaluated the reproducibility of response for a number of variables, including platelet number and time after donation. The effect of inhibition of the two major platelet feedback mediators, ADP and thromboxane A(2) (TxA(2)), was investigated using the P2Y(1) and P2Y(12) receptor antagonists, MRS2179 and AR-C67085, and the cyclooxygenase inhibitor, indomethacin. The results demonstrate that, if used within certain boundaries, the investigation of platelet aggregation and secretion is a powerful way to discriminate between differing pathways of platelet activation. The present data-set are an invaluable resource to the clinical laboratory to aid evaluation of patients with suspected platelet-based bleeding disorders.
authors.affiliation: Centre for Cardiovascular Sciences, Division of Medical Sciences, Institute of Biomedical Research, Wolfson Drive, The Medical School, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.
authors.forename: Ban B
authors.initials: BB
authors.lastname: Dawood
authors.forename: Jonathan
authors.initials: J
authors.lastname: Wilde
authors.forename: Steve P
authors.initials: SP
authors.lastname: Watson
mesh_terms: D000244:Adenosine Diphosphate / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D000249:Adenosine Monophosphate / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000737:chemistry / Q000378:metabolism*; D001792:Blood Platelets / Q000378:metabolism* / Q000473:pathology; D016861:Cyclooxygenase Inhibitors / Q000737:chemistry / Q000494:pharmacology; D003937:Diagnosis, Differential; D005260:Female; D006470:Hemorrhage / Q000175:diagnosis* / Q000378:metabolism*; D006801:Humans; D007213:Indomethacin / Q000737:chemistry / Q000494:pharmacology; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects; D010979:Platelet Function Tests / Q000592:standards; D058910:Purinergic P2 Receptor Agonists; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2 / Q000378:metabolism; D058472:Receptors, Purinergic P2Y1; D058925:Receptors, Purinergic P2Y12; D012015:Reference Standards; D022142:Secretory Vesicles / Q000378:metabolism; D013928:Thromboxane A2 / Q000378:metabolism*
chemical_list: C117445:AR C67085MX; D016861:Cyclooxygenase Inhibitors; C111914:N(6)-methyl-2'-deoxyadenosine 3',5'-diphosphate; C546382:P2RY1 protein, human; C548576:P2RY12 protein, human; D058910:Purinergic P2 Receptor Agonists; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2; D058472:Receptors, Purinergic P2Y1; D058925:Receptors, Purinergic P2Y12; D000249:Adenosine Monophosphate; D013928:Thromboxane A2; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D007213:Indomethacin