Chronic Hemolytic Anemia with Erythrocyte Fragility to Cold and Acid : I. Clinical and Laboratory Data of Two Cases, with Special Reference to the Cell Abnormality

Two cases previously diagnosed as aplastic anemia were found to have abnormal susceptibility of the red blood cells to hemolysis after chilling and after addition of acid in the presence of their own as well as control serum. The serum of the patients had no such effect on control erythrocytes. This erythrocyte abnormality was accompanied by a severe anemia of the macrocytic type, slight reticulocytosis, depression of granulocytes and platelets, and erythropoietic hyperactivity of the bone marrow in the early stages and hypoactivity in the late stages. Increased blood destruction was evidenced not by jaundice, but by persistent hyperhemoglobinemia in the serum and increased iron excretion in the urine, without nocturnal intensification. Chilling in vivo produced hemoglobinuria in Case 1, but only slight evidence of increased blood destruction in Case 2. Administration of large doses of ammonium chloride failed to produce hemoglobinuria in either case, although evidence of an increase in blood destruction was detectable. Both patients had historical and serologic evidence of syphilis. Autopsy of Case 1 showed, in addition to syphilitic aortitis, marked hemosiderosis of the kidneys, liver, spleen and lymph nodes.

These were clearly not cases of paroxysmal hemoglobinuria é frigore (Donath-Landsteiner). They resembled cases of chronic hemolytic anemia with nocturnal paroxysmal hemoglobinuria (Marchiafava-Micheli), but the erythrocyte fragility to chilling, the absence of nocturnal increase in the hemolytic process and the presence of syphilis rendered the acceptance of such diagnosis difficult.