Pathogenesis of a bleeding disorder characterized by platelet unresponsiveness to thromboxane A_2

本文对6例血小板对血栓素A_2（TXA_2）无反应性患者的TXA_2受体突变进行了研究，发现所有患者的TXA_2受体（Arg <60>→ Leu）均异常，其中4例为纯合型，2例为杂合型。而后者TXA_2诱导的IP_3形成和Ca^&lt;2+&gt;动员均在正常范围内，提示该突变是该血小板疾病中唯一的异常，在该突变杂合子患者中，突变型TXR通过独立于磷脂酶C的机制抑制野生型受体介导的血小板聚集。

We investigated the mutation of the thromboxane A_2 (TXA_2) receptor in six patients with platelet unresponsiveness to TXA_2, and found that all of the patients patients have the same abnormality of the TXR (Arg^<60> to Leu), although four patients are homozygous and two patients are heterozygous for this mutation. However, in the latter patients, TXA_2-induced IP_3 formation and Ca^<2+> mobilization were within normal limilts.These results suggest that this mutation is the only abnormality which has been found in this platelet disorder, and that, in patients with heterozygous for this mutation, the mutant type TXR suppress the wild-type receptor mediated platelet aggregation by the mechanism independent of phospholipase C.