Abnormal platelet response to thromboxane A2.
Abnormal platelet response to thromboxane A2.
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血小板对血栓素 A2 的异常反应。
DOI：
10.1172/jci110221
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发表时间：
1981
期刊：
影响因子：
--
通讯作者：
Y. Chen
中科院分区：
文献类型：
--
作者：
K. Wu;G. L. Le Breton;H. Tai;Y. Chen
为了确定遗传性原发性血小板释放障碍的发病机制，研究了花生四烯酸通过环加氧酶途径的代谢。在花生四烯酸钠或血栓素A2 （TXA2）激动剂U46619的刺激下，受试者的血小板表现出缺陷释放反应和第二波聚集。血小板对U46619缺乏反应表明该缺陷超出了血栓素合成酶水平。此外，血栓素B2 （TXB2）的形成（558.52 ng/10(8)个血小板）在正常范围内（574.29 +/- SD 27.39 ng/10(8)个血小板），TXA2的形成似乎足以聚集正常血小板。结果表明血小板对TXA2的反应异常。花生四烯酸钠诱导的正常富血小板血浆中形成的TXA2导致孕鼠血小板聚集失败，证实了这一观点。为了进一步了解，我们测定了血小板环(c) AMP的含量。前列环素可显著提高受试者血小板cAMP水平，与正常值相当。U46619在正常受试者中抑制前列腺素i2诱导的cAMP升高，但在患者中无此作用。我们得出结论，在这个家族中观察到的主要释放障碍是由于血小板对TXA2的异常反应，可能是由于TXA2/PGH2受体异常。
To determine the pathogenetic mechanism of a hereditary primary platelet release disorder, arachidonic acid metabolism via the cyclooxygenase pathway was investigated. The propositus' platelets exhibited defective release reaction and second-wave aggregation when stimulated by sodium arachidonate or U46619, a thromboxane A2 (TXA2) agonist. The lack of platelet response to U46619 suggested that the defect was beyond the thromboxane synthetase level. Furthermore, thromboxane B2 (TXB2) formation in the propositus' platelets (558.52 ng/10(8) platelets) was within the normal range (574.29 +/- SD 27.39 ng/10(8) platelets) and TXA2 formation appeared to be adequate for aggregating normal platelets. The results were indicative of an abnormal platelet response to TXA2. Failure of the propositus' platelets to aggregate in response to TXA2 formed in normal platelet-rich plasma induced by arachidonate confirmed this notion. To gain further insight, platelet cyclic (c) AMP content was determined. Prostacyclin induced a significant elevation of the propositus' platelet cAMP level comparable to normal values. U46619 suppressed prostaglandin I2-induced cAMP elevation in normal subjects but had no such effect in the patient. We conclude that the primary release disorder observed in this kindred is due to an abnormal platelet respnse to TXA2 possibly because of TXA2/PGH2 receptor abnormalities.