Determinants of erythrocyte size in chronic liver disease.

E RYTHROCYTE MACROCYTOSIS has been observed commonly in association with chronic liver disease; estimates of its frequency vary from 37 to 75 per cent.1'2 That the large erythrocytes, as seen on blood films, are a heterogeneous group was recognized by Bingham, who distinguished three types: " thick macrocytes, " " thin macrocytes " and " target macrocytes. " 3 His observations suggested that " thin macrocytosis " was the most common red cell abnormality in patients with chronic hepatic disease. These thin macrocytes were found to have normal cell volume and were thought to originate from " macronormoblasts. " They differed from " target macrocytes " chiefly by their appearance on blood films, but their thickness and diameter were in ranges similar to those of target cells. Recent studies of Cooper and Jandl4 have shown that target cells of patients with jaundice, particularly of the obstructive type, have a moderate excess of membrane cholesterol leading to an increase of surface area without increase in volume. This alteration in the surface-volume ratio is reversible by normalizing the plasma environment. Neerhout has presented data suggesting that the lipid content of the erythrocyte stroma, especially phosphatidyl choline increases with the severity of the liver disease.5 The mean corpuscular volume (MCV) also tended to be larger in the patients with more serious hepatic disease, but there was no correlation between MCV and lipid content of the stroma. The present study deals only with the macrocytosis characterized by increased volume as determined by electronic sizing equipment.6 By the use of such equipment for red cell sizing we observed variations in the volume of the red cells from patients with hepatic disease during various stages of their clinical course. We then undertook to serially determine the red cell size in a group of patients with chronic liver disease and to ascertain with which factors cell size changes were associated.