On the death in megaloblastic anemia; clinical and experimental aspects

Megaloblastic anemia(MA) still leaves us with some questions unanswered, despite the fact that its treatment is complete at the mid-turn of this Century. Two aspects of deaths in this disease, patientsʹ death and marrow cellsʹ death were examined. The first relates to the long-term prognosis of patients with pernicious anemia(PA), and the second to the laboratory evidence for the apoptotic cell death of the blood cells. A total of 385 patients with MA was collected in collaboration with 21 institutations. PA comprised 62 %(240 cases,M/F ; 1.3/1), while 33 %(128 cases) were due to agastric B12 deficiency. Folate deficiency was 2 %. Patients were diagnosed over the past 30 years. As for PA the mean age at diagnosis and observation period were 65 y/o and 5.4 years, respectively. Among PA patients 26 deaths were recorded, which were ascribed to an apparently unrelated causes in most cases.The survival plot was compared to those which were obtained on a model population constructed using annual report of the “life expectancy table” published by the Japanese Authority. Results indicted that patients with PA, when appropriately treated, enjoy smooth and uneventful lives. Three laboratory approaches were taken for elucidation of the evidence of apoptosis using fresh untreated bone marrow cells from 6 patients. The apoptotic bodies were not detected in the flowcytometric analysis, and DNA ladder formation was not observed in all specimens. Furthermore, the frequency of apoptotic signals was not increased significantly according to TUNEL method. These observations do not support the apoptosis mechanism as a mode of intramedullar y cell death.