Heterogeneous defects of platelet secretion and responses to weak agonists in patients with bleeding disorders.
Eleven patients with mild bleeding disorders had as a common abnormality, impaired platelet aggregation and secretion with low concentrations (0.5-1.0 micrograms/ml) of collagen and, in most cases, an absence of second phase aggregation with epinephrine. Platelet granule contents were normal, ruling out storage pool deficiency. To characterize further the platelet abnormalities, we measured aggregation, 14C-5HT secretion, and TxB2 formation induced by a variety of platelet agonists. In eight of the 11 patients we observed decreased initial rates as well as extents of aggregation with one or more weak agonists (ADP, epinephrine, thromboxane A2 and the endoperoxide analogue U44069), i.e. agonists which induced secretion only as a result of aggregation, but normal responses to strong agonists such as arachidonate and high (10 micrograms/ml) concentrations of collagen, which can induce secretion in the presence or absence of aggregation. In all of these patients, TxB2 formation with arachidonate and all concentrations of collagen was normal. The platelet defects in these eight patients have been designated as weak agonist response defects (WARDs). In contrast, the initial aggregation responses to all weak agonists were normal in the three other patients, while secretion and TxB2 formation induced by strong agonists were impaired. Thus, in contrast to the eight patients above, the platelet defects in these three patients were characteristic of defects in the secretion response per se. The results obtained in the 11 patients studied indicate that these types of platelet disorders, previously referred to as primary secretion defects, include defects in the initial platelet responses which precede secretion (WARD) as well as defects in the secretory mechanism per se. Both groups of defects appear to be heterogeneous in nature.
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Department of Medicine, Columbia University College of Physicians and Surgeons, New York.
Weiss
H J
HJ
D000328:Adult; D000368:Aged; D001791:Blood Platelet Disorders / Q000097:blood*; D001792:Blood Platelets / Q000378:metabolism*; D003594:Cytoplasmic Granules / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects; D012701:Serotonin / Q000097:blood; D013929:Thromboxane B2 / Q000097:blood
D012701:Serotonin; D013929:Thromboxane B2