Tomer A, Scharf R E, McMillan R, Ruggeri Z M, Harker L A
Division of Hematology and Oncology, Emory University School of Medicine, Atlanta, GA 30322.
Eur J Haematol. 1994 Apr;52(4):193-200. doi: 10.1111/j.1600-0609.1994.tb00645.x.
Platelets and megakaryocytes have been characterized in a Bernard-Soulier syndrome (BSS) kindred with respect to glycoprotein (GP) membrane receptors and measurements of thrombocytopoiesis. The index patient exhibited lifelong bleeding tendency, moderate thrombocytopenia (35 x 10(9)/l), giant platelets (mean platelet volume 12.5 microns 3 compared to 7.5 +/- 1.5 microns 3 in normals), absent ristocetin-induced platelet agglutination and absent binding of von Willebrand factor (vWF). Flow-cytometric analysis revealed absent platelet binding (0-2%) of monoclonal antibodies (mAb, LJ-P3, LJ-Ib1 and LJ-Ib10) directed against distinct epitopes on membrane GPIb alpha of the GPIb-IX complex, and normal binding of LJ-P4 mAb directed against GPIIb/IIIa complex (relative to increased platelet surface area). Marrow megakaryocytes also failed to express GPIb-IX complex, but demonstrated normal expression of GPIIb/IIIa. Among 6 asymptomatic family members, the patient's mother and 2 of his 4 children exhibited approximately 50% binding of anti-GPIb alpha mAb to their platelets by both flow cytometry and direct binding studies using 125I-vWF, 125I-LJ-Ib1 and 125I-LJ-Ib10 mAb. Marrow megakaryocytes were increased in the average cell volume and cytoplasmic granularity with a corresponding increase in ploidy (46% > 16N compared to 22 +/- 5% in normal individuals), a pattern typical of megakaryocytes stimulated by thrombocytopenia. Autologous 111In-platelet life span was shortened to 4.1 days (compared with 9.5 +/- 0.5 days in normal subjects), and the turnover of platelet mass in the circulation was near normal. The data directly demonstrate that the platelet membrane GPIb-IX defect in BSS originates in megakaryocytes at all levels of cell maturation, and exclude the possibility that the receptor abnormality is acquired during cell maturation or after platelets are released into the circulation. Since marrow megakaryocytes exhibited cellular changes consistent with stimulated megakaryocytopoiesis, these results also suggest that thrombocytopenia in this kindred of BSS is a consequence of both decreased platelet survival and ineffective platelet production.
就糖蛋白（GP）膜受体和血小板生成的测量而言，已对患有伯纳德 - 索利尔综合征（BSS）的一个家族中的血小板和巨核细胞进行了特征分析。索引患者表现出终生出血倾向、中度血小板减少（35×10⁹/L）、巨大血小板（平均血小板体积为12.5立方微米，而正常人为7.5±1.5立方微米）、瑞斯托霉素诱导的血小板凝集缺失以及血管性血友病因子（vWF）结合缺失。流式细胞术分析显示，针对GPIb - IX复合物膜GPIbα上不同表位的单克隆抗体（mAb，LJ - P3、LJ - Ib1和LJ - Ib10）的血小板结合缺失（0 - 2%），而针对GPIIb/IIIa复合物的LJ - P4 mAb的结合正常（相对于增加的血小板表面积）。骨髓巨核细胞也未能表达GPIb - IX复合物，但显示出GPIIb/IIIa的正常表达。在6名无症状家族成员中，患者的母亲及其4个孩子中的2个通过流式细胞术以及使用¹²⁵I - vWF、¹²⁵I - LJ - Ib1和¹²⁵I - LJ - Ib10 mAb的直接结合研究，显示抗GPIbα mAb与他们的血小板的结合约为50%。骨髓巨核细胞的平均细胞体积和细胞质颗粒度增加，倍性相应增加（46%＞16N，而正常个体为22±5%），这是血小板减少刺激的巨核细胞的典型模式。自体¹¹¹In - 血小板寿命缩短至4.1天（与正常受试者的9.5±0.5天相比），循环中血小板质量的周转率接近正常。数据直接表明，BSS中的血小板膜GPIb - IX缺陷起源于细胞成熟各阶段的巨核细胞，并排除了受体异常是在细胞成熟过程中或血小板释放到循环后获得的可能性。由于骨髓巨核细胞表现出与受刺激的巨核细胞生成一致的细胞变化，这些结果还表明，该BSS家族中的血小板减少是血小板存活减少和血小板生成无效共同作用的结果。
