HETEROGENEOUS DEFECTS OF PLATELET SECRETION AND RESPONSES TO WEAK AGONISTS IN PATIENTS WITH BLEEDING DISORDERS
HETEROGENEOUS DEFECTS OF PLATELET SECRETION AND RESPONSES TO WEAK AGONISTS IN PATIENTS WITH BLEEDING DISORDERS
复制标题
DOI：
10.1111/j.1365-2141.1988.tb04179.x
复制
发表时间：
1988-01-01
影响因子：
6.5
通讯作者：
WEISS, HJ
中科院分区：
文献类型：
--
作者：
LAGES, B;WEISS, HJ
11名患有轻度出血性疾病的患者具有常见的异常，受损的血小板聚集和低浓度（0.5-1.0 μ g/ml）胶原蛋白的分泌，并且在大多数情况下，不存在与肾上腺素的第二相聚集。血小板颗粒含量正常，排除储库缺乏。为了进一步表征血小板异常，我们测量了聚集。14 C-5 HT分泌和多种血小板激动剂诱导的TxB 2形成。在11例患者中的8例中，我们观察到一种或多种弱激动剂的初始速率和聚集程度降低（ADP、肾上腺素、血栓烷A2和内过氧化物类似物U44069），即仅作为聚集的结果诱导分泌的激动剂，但对强激动剂如花生四烯酸和高浓度的花生四烯酸的正常反应，（10 μ g/ml）浓度的胶原蛋白，其在存在或不存在聚集的情况下诱导分泌。在所有这些患者中，花生四烯酸和所有浓度的胶原蛋白的TxB 2形成均正常。这8例患者的血小板缺陷被称为弱激动剂反应缺陷（WARD）。相反，在其他三名患者中，对所有弱激动剂的初始聚集反应均正常，而由强激动剂诱导的分泌和TxB 2形成受损。因此，与上述8例患者相比，这3例患者的血小板缺陷是分泌反应本身缺陷的特征。研究的11例患者中获得的结果表明，这些类型的血小板疾病（以前称为原发性分泌缺陷）包括分泌前的初始血小板反应（WARD）缺陷以及分泌机制本身的缺陷。这两组缺陷似乎是异质性的性质。
Eleven patients with mild bleeding disorders had as a common abnormality, impaired platelet aggregation and secretion with low concentrations (0.5-1.0 .mu.g/ml) of collagen and, in most cases, an absence of second phase aggregation with epinephrine. Platelet granule contents were normal, ruling out stroage 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 .mu.g/ml) concentrations of collagen, which an induce secretion in the presence of 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 platlet 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.