Milton J G, Frojmovic M M, Tang S S, White J G
Am J Pathol. 1984 Feb;114(2):336-45.
The characteristics of spontaneous platelet aggregation (SPA) in a hereditary giant platelet syndrome (Montreal platelet syndrome, MPS) are examined. SPA was quantitated by microscopy from the decrease in single platelets in platelet-rich plasma (PRP). In contrast to normal donors, a significant proportion (20-50%) of platelets in MPS whole blood and PRP occurred in microaggregates typically containing 2-6 disk-shaped platelets. Stirring MPS-PRP at 1000 rpm for 10 minutes further increased the fraction of platelets in aggregates by 10-170%, the percentage increase not being correlated to the donor's platelet count (5000-220,000 microliters-1). Normal platelets resuspended in MPS platelet-poor plasma (PPP) did not undergo SPA, whereas MPS platelets resuspended in normal PPP or Ca2+-free, fibrinogen-free Tyrode's continued to show SPA. The increase in SPA could be inhibited by 10 microM prostaglandin (PG) E1, 150 mM ASA or glutaraldehyde or formaldehyde fixation; however, it was not inhibited by 10 nM PGI2 and was only partially inhibited by 1 microM 2-chloroadenosine and 1-10 units/ml apyrase. SPA in Acid-citrate-dextrose-PRP was much less than in PRP; however, SPA reoccurred on returning the platelets to platelet-free plasma or Tyrode's. Platelet aggregation (PA) could be increased over that due to SPA alone by the addition of adenosine diphosphate, adrenaline, collagen, ionophore A-23187, arachidonic acid and ristocetin, with results suggesting that the response to these agents is normal. The ristocetin-induced increase in PA was completely blocked by an IgG specific for Bernard-Soulier syndrome. In contrast, MPS platelets had a reduced sensitivity to thrombin, which appeared to be more pronounced at low platelet counts. There was no correlation between the thrombin insensitivity and the extent of SPA. Total adenosine triphosphate (ATP) and thrombin-induced release of ATP and platelet factor 4 appeared normal for MPS platelets. The ultrastructural features of MPS platelets were within normal limits except for an increased frequency of giant granules. SPA was observed for 5/5 MPS donors, but only one of three MPS donors' platelets evaluated for glycoprotein I and sialic acid content showed any measurable reduction as compared with normal controls. The above observations point to the existence of an as yet undetermined anomaly of MPS plasma membrane related to a fibrinogen and Ca2+ independent form of platelet aggregation.
研究了遗传性巨大血小板综合征（蒙特利尔血小板综合征，MPS）中自发性血小板聚集（SPA）的特征。通过显微镜观察富含血小板血浆（PRP）中单个血小板的减少来定量SPA。与正常供体相比，MPS全血和PRP中相当一部分（20 - 50%）的血小板以微聚集体形式存在，这些微聚集体通常包含2 - 6个盘状血小板。将MPS - PRP以1000转/分钟搅拌10分钟，可使聚集体中血小板的比例进一步增加10 - 170%，增加的百分比与供体血小板计数（5000 - 220,000微升⁻¹）无关。重悬于MPS乏血小板血浆（PPP）中的正常血小板未发生SPA，而重悬于正常PPP或无Ca²⁺、无纤维蛋白原的台氏液中的MPS血小板继续表现出SPA。SPA的增加可被10微摩尔前列腺素（PG）E1、150毫摩尔阿司匹林或戊二醛或甲醛固定所抑制；然而，它不受10纳摩尔前列环素（PGI2）抑制，仅被1微摩尔2 - 氯腺苷和1 - 10单位/毫升腺苷三磷酸双磷酸酶部分抑制。酸性枸橼酸盐葡萄糖 - PRP中的SPA远低于PRP中的；然而，将血小板重新置于无血小板血浆或台氏液中时，SPA会再次出现。通过添加二磷酸腺苷、肾上腺素、胶原、离子载体A - 23187、花生四烯酸和瑞斯托霉素，可使血小板聚集（PA）超过仅由SPA引起的水平，结果表明对这些试剂的反应是正常的。瑞斯托霉素诱导的PA增加被针对伯纳德 - 索利尔综合征的特异性IgG完全阻断。相比之下，MPS血小板对凝血酶的敏感性降低，在低血小板计数时这种情况似乎更明显。凝血酶不敏感性与SPA程度之间无相关性。MPS血小板的总三磷酸腺苷（ATP）以及凝血酶诱导的ATP和血小板因子4释放似乎正常。除了巨大颗粒的频率增加外，MPS血小板的超微结构特征在正常范围内。5名MPS供体中有5名观察到了SPA，但在评估糖蛋白I和唾液酸含量的3名MPS供体中，只有1名的血小板与正常对照相比显示出任何可测量的减少。上述观察结果表明存在一种尚未确定的MPS质膜异常，与纤维蛋白原和Ca²⁺无关的血小板聚集形式有关。
