Bernard-Soulier syndrome: quantitative characterization of megakaryocytes and platelets by flow cytometric and platelet kinetic measurements.
Bernard-Soulier syndrome: quantitative characterization of megakaryocytes and platelets by flow cytometric and platelet kinetic measurements.
复制标题
Bernard-Soulier 综合征：通过流式细胞术和血小板动力学测量对巨核细胞和血小板进行定量表征。
DOI：
10.1111/j.1600-0609.1994.tb00645.x
复制
发表时间：
1994
影响因子：
3.1
通讯作者：
Harker,LA
中科院分区：
文献类型：
--
作者：
Tomer,A;Scharf,RE;McMillan,R;Ruggeri,ZM;Harker,LA
血小板和巨核细胞在Bernard‐Soulier综合征（BSS）家族中与糖蛋白（GP）膜受体和血小板生成测量有关。指标患者表现为终身出血倾向，中度血小板减少（35 × 109/1），血小板巨大（平均血小板体积12.5 μm3，正常人7.5±1.5 μm3），无瑞索司汀诱导的血小板凝集，无血管性血液病因子（vWF）结合。流式细胞分析显示，针对GPIb - IX复合物细胞膜上不同表位的单克隆抗体（mAb、LJ‐P3、LJ‐Ibl和LJ‐Ibl0）缺乏血小板结合（0-2%），而针对GPIIb/IIIa复合物的LJ‐P4单克隆抗体的结合正常（相对于血小板表面积增加）。骨髓巨核细胞也不能表达GPIb - IX复合物，但GPIIb/IIIa的表达正常。在6名无症状的家庭成员中，患者的母亲和他的4个孩子中的2个通过流式细胞术和使用125I - vWF、125I - LJ - Ibl和125I - LJ - Ibl0单抗的直接结合研究显示，抗GPIbα单抗与血小板的结合率约为50%。骨髓巨核细胞的平均细胞体积和细胞质粒度增加，相应的倍性增加（46% bbb16n，而正常人为22±5%），这是血小板减少症刺激巨核细胞的典型模式。自体血小板寿命缩短至4.1天（正常受试者为9.5±0.5天），循环中血小板质量的周转量接近正常。这些数据直接证明了BSS中血小板膜GPIb‐IX缺陷起源于细胞成熟的所有水平的巨核细胞，并排除了受体异常在细胞成熟过程中或血小板释放进入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，这类BSS中的血小板减少是血小板存活减少和血小板产生无效的结果。
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 × 109/1), giant platelets (mean platelet volume 12.5 μm3compared to 7.5 ± 1.5 μm3in 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‐Ibl and LJ‐Ibl0) directed against distinct epitopes on membrane GPIbα 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‐GPIbα mAb to their platelets by both flow cytometry and direct binding studies using125I‐vWF,125I‐LJ‐Ibl and125I‐LJ‐Ibl0 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. Autologous111In‐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.