Mechanism of megaloblastic anemia combined with hemolysis

Megaloblastic anemia (MA) patients often exhibit hemolysis, but it is not clear whether there are other hemolytic mechanisms in addition to intramedullary hemolysis. We retrospectively analyzed the clinical characteristics of 124 MA patients, measured erythrocyte physical parameters in two patients with hemolysis and one healthy volunteer by atomic force microscopy, and measured 18F-FDG uptake in one MA patient with hemolysis. In multivariate analysis, hemolysis was associated with mean corpuscular volume (MCV) and indirect bilirubin. A receiver operating characteristic curve analysis, with sensitivity of 83.1% and specificity of 68.7%, suggested that the MCV cutoff value that predicts hemolysis is 116.4 fL. Hb was negatively correlated with MCV in the hemolysis group (r = -0.317, P = 0.007) but not in the nonhemolysis group. The erythrocyte peak-valley value, average cell surface roughness and surface area in the MA patients with hemolysis were significantly lower than those in controls (P < 0.05). 18F-FDG uptake by the liver and spleen was diffuse and increased in MA patients undergoing hemolysis. MA combined with extramedullary hemolysis could be caused by macrophages removing mechanically damaged erythrocytes and the retention of erythrocytes with decreased deformability when blood circulates through narrow spaces in the liver and spleen.