Cowan D H, Graham R C, Baunach D
J Clin Invest. 1975 Jul;56(1):188-200. doi: 10.1172/JCI108067.
The ultrastructure and adenine nucleotide metabolism of platelets from patients with acute leukemia were studied to elucidate possible mechanisms for the platelet dysfunction observed in this clinical setting. Nonstimulated (resting) platelets from leukemic patients varied greatly in size; exhibited marked variation in the number of alpha granules present per cell; had poorly delineated circumferential bands of microtubules; and often grossly dilated open channel systems or cytoplasmic vacuolization. The intracellular concentrations of ATP and ADP were significantly below normal, and the specific radioactivity of ATP and ADP of nonstimulated platelets in leukemia was equivalent to or exceeded that seen in stimulated normal platelets. Addition of ADP or collagen to platelets from leukemic patients was followed by retarded and incomplete shape change, delayed and incomplete centripetal migration of subcellular organelles, impaired degranulation, and the formation of loose aggregates composed of relatively few platelets. Stimulation of "leukemic" platelets with collagen led to the release of significantly subnormal amounts of ATP and ADP and no significant change in the specific radioactivity of the intracellular nucleotides. In contrast to the results in normal platelets, the conversion of ATP to inosine monophosphate and hypoxanthine in platelets in leukemia failed to increase significantly with collagen stimulation. The results indicate that abnormalities exist in the storage pool of adenine nucleotides and the release mechanism of platelets in acute leukemia. These defects appear to contribute to an impairment in the release reaction in these platelets. Many of the ultrastructural and metabolic defects seen in acute leukemia occur in platelets in preleukemia.
对急性白血病患者血小板的超微结构和腺嘌呤核苷酸代谢进行了研究，以阐明在这种临床情况下观察到的血小板功能障碍的可能机制。白血病患者未受刺激（静息）的血小板大小差异很大；每个细胞中存在的α颗粒数量有明显变化；微管的周向带界限不清；并且常有明显扩张的开放通道系统或细胞质空泡化。ATP和ADP的细胞内浓度显著低于正常水平，白血病患者未受刺激血小板中ATP和ADP的比放射性等于或超过正常受刺激血小板中的比放射性。向白血病患者的血小板中添加ADP或胶原后，会出现形状变化延迟且不完全、亚细胞器向心迁移延迟且不完全、脱颗粒受损以及由相对较少血小板组成的松散聚集体形成。用胶原刺激“白血病”血小板会导致ATP和ADP的释放量显著低于正常水平，且细胞内核苷酸的比放射性无显著变化。与正常血小板的结果相反，白血病患者血小板中ATP向肌苷单磷酸和次黄嘌呤的转化在胶原刺激下未能显著增加。结果表明，急性白血病患者血小板中腺嘌呤核苷酸的储存池和释放机制存在异常。这些缺陷似乎导致了这些血小板释放反应的受损。急性白血病中出现的许多超微结构和代谢缺陷在白血病前期的血小板中就已出现。
