Humoral factors in aplastic anemia: relationship of liver dysfunction to lack of serum stimulation of bone marrow growth in vitro

Sera from 26 patients with aplastic anemia (AA) were examined for their effects in vitro on autologous AA marrow and heterologous normal bone marrow proliferation. Two groups of patients with respect to serum activity were defined, one group (13 patients) in which serum stimulated autologous and normal marrow cell growth relative to the effects of normal serum, and another in which serum was nonstimulatory (5 patients within the normal range, 8 patients inhibitory). The consistently demonstrable effects of these individual sera on cultured normal marrow cell 3 H-TdR incorporation, 3 H-TdR labeling index, cell counts, and morphologic differentials, and on overall autologous AA marrow cell growth, did not relate to patient age, peripheral blood counts, bone marrow cellularity or content, the presence or absence of serum cytotoxicity, or serum erythropoietin content. Ten of thirteen with stimulatory sera had no discernible cause for their AA. The other 13 patients, whose sera were nonstimulatory, were those who had precedent histories of Australia antigen (HAA)-negative hepatitis and/or biochemical evidence of active liver dysfunction (10/13). These patients in whom liver disease and AA appeared to coincide were more likely to be males (8/10 patients) with type O blood (6/8 males). The serum inhibition could be neutralized in vitro by mixing that serum with stimulatory serum obtained from patients with normal bone marrow during drug-induced aplasia.