Lages B, Sussman I I, Levine S P, Coletti D, Weiss H J
Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY 10019, USA.
J Lab Clin Med. 1997 Mar;129(3):364-75. doi: 10.1016/s0022-2143(97)90185-2.
We report studies on a new patient with gray platelet syndrome (GPS, alpha-storage pool deficiency). Her lifelong bleeding history is associated with platelet abnormalities characteristic of GPS including mild to moderate thrombocytopenia, a population of abnormally large platelets, and specific deficiencies of alpha-granule constituents and morphologically typical alpha-granules. Platelet function studies showed normal aggregation responses to adenosine diphosphate, epinephrine, collagen, arachidonate, and ristocetin but impaired activation responses to thrombin and a thrombin receptor-activating peptide (T1 peptide). These impaired responses included T1 peptide-induced aggregation, thrombin-induced adenine nucleotide secretion, and thrombin-induced (Ca2+)i increases. The impairment of the thrombin-induced (Ca2+)i increase was observed as a substantially slower initial rise in (Ca2+)i levels and a smaller maximum (Ca2+)i increase compared with the responses obtained in normal platelets and are thus similar to those reported previously in another patients with GPS. Flow cytometric measurements of the binding of two distinct monoclonal antibodies against the functional thrombin receptor indicated the presence of a normal number of receptors and normal receptor cleavage by thrombin in the GPS platelets, providing additional support for the hypothesis presented in previous studies that the thrombin activation defect in GPS platelets occurs subsequent to the interaction of thrombin with its receptor. The alpha-granule deficiency in this patient was associated with an approximately 50% decrease in the content and surface expression of the alpha-granule membrane-specific protein P-selectin in contrast to a previous report of normal amounts of P-selectin in the platelets of two related patients with GPS. This finding raises the possibility that the alpha-granule deficiency in GPS may be expressed in different phenotypes characterized by differences in the amount or constitution of residual alpha-granule membranes present in GPS platelets.
我们报告了对一名新的灰色血小板综合征（GPS，α-颗粒贮存池缺乏症）患者的研究。她的终生出血史与GPS特有的血小板异常有关，包括轻度至中度血小板减少、一群异常大的血小板，以及α-颗粒成分和形态典型的α-颗粒的特定缺乏。血小板功能研究显示，对二磷酸腺苷、肾上腺素、胶原、花生四烯酸和瑞斯托菌素的聚集反应正常，但对凝血酶和凝血酶受体激活肽（T1肽）的激活反应受损。这些受损反应包括T1肽诱导的聚集、凝血酶诱导的腺嘌呤核苷酸分泌，以及凝血酶诱导的细胞内钙离子（Ca2+）i增加。与正常血小板的反应相比，观察到凝血酶诱导的（Ca2+）i增加受损，表现为（Ca2+）i水平的初始上升明显较慢，最大（Ca2+）i增加较小，因此与先前报道的另一名GPS患者的情况相似。对两种针对功能性凝血酶受体的不同单克隆抗体结合的流式细胞术测量表明，GPS血小板中存在正常数量的受体，且凝血酶对受体的切割正常，这为先前研究中提出的假设提供了额外支持，即GPS血小板中的凝血酶激活缺陷发生在凝血酶与其受体相互作用之后。与先前报道的两名相关GPS患者血小板中P-选择素含量正常的情况相反，该患者的α-颗粒缺乏与α-颗粒膜特异性蛋白P-选择素的含量和表面表达降低约50%有关。这一发现增加了一种可能性，即GPS中的α-颗粒缺乏可能以不同表型表现出来，其特征是GPS血小板中存在的残余α-颗粒膜的数量或组成不同。
