IMPAIRED PLATELET RESPONSE TO THROMBOXANE-A2 AND DEFECTIVE CALCIUM MOBILIZATION IN A PATIENT WITH A BLEEDING DISORDER

  • 1 January 1981
    • journal article
    • research article
    • Vol. 57  (3) , 545-552
Abstract
Platelet aggregation, secretion and thromboxane formation induced by various agonists, including arachidonate, prostaglandin G2 (PGG2), and thromboxane A2 (TxA2), were examined in a patient with a bleeding disorder who was previously reported to have a TxA2-related defect. Aggregation and 14C-5HT [5-hydroxytryptamine] secretion were decreased, and no TxB2 formation occurred in response to ADP, epinephrine or collagen. Arachidonate-induced aggregation and TxB2 formation, and PGG2-induced aggregation (but not TxB2 formation) were impaired at low agonist concentrations. The patient''s platelets did not aggregate in response to TxA2 generated from arachidonate in normal platelets, but were capable of synthesizing TxA2 from both arachidonate and PGG2. Aggregation and secretion induced by low concentrations of the ionophore A23187 [calcimycin] were impaired in platelet-rich plasma (PRP) and in gel-filtered platelets [GFP] in the absence of extracellular Ca; these responses became normal at higher A23187 concentrations or, in GFP, at low A23187 concentrations in the presence of exogenous Ca. The TxA2 defect in this patient does not result from a thromboxane synthetase deficiency, but may be due to impaired mobilization of platelet Ca, and thus are consistent with the possibility that TxA2 may act as a Ca ionophore.