ACQUIRED HEMOLYTIC ANEMIA : I. THE RELATION OF ERYTHROCYTE ANTIBODY PRODUCTION TO ACTIVITY OF THE DISEASE. II. THE SIGNIFICANCE OF THROMBOCYTOPENIA AND LEUKOPENIA

1. Observations of 11 patients with acquired hemolytic anemia are reported.

2. In contrast to patients with congenital hemolytic jaundice, all patients in this group exhibited evidence of sensitization of their erythrocytes by an antibody-like agent. In all patients studied there was abnormal destruction of transfused cells in vivo.

3. The sensitizing agent was found to be adsorbed on the erythrocytes when it could not be demonstrated in the serum. A rough method of assay of the amount adsorbed was devised by making serial dilutions of the anti-globulin serum. With this technic a fairly consistent correlation was found between the amount of antibody on the cell and activity of the disease.

4. Splenectomy when successful appears to exert a curative effect by sharply reducing the amount of antibody substance on the cell. Patients who had not responded to splenectomy in the past showed evidence of saturation of their cells with adsorbed antibody. The erythrocytes of patients who had responded to splenectomy and were in remission when studied showed distinctly less antibody on the cell by the same technique.

5. Two patients were observed to enter spontaneous remission after a long period of activity. The onset of remission in both was associated with a decrease in the amount of adsorbed immune body. However, one patient has shown evidence of return of antibody production without immediate recurrence of the hemolytic anemia. This inconsistency is not explained.

6. The tendency toward spherocytosis as measured by increased osmotic fragility may or may not be present in acquired hemolytic anemia. Prior to splenectomy the most marked increase in hypotonic fragility was observed in the patient with the most active disease. Continued activity of the disease following splenectomy was productive of the most extreme increases in spherocytosis. This suggests that the spherocytic cells are removed from the circulation by the spleen.

7. Agglutination of red cells when the amount of adsorbed antibody reaches a critical level, together with such other phenomenon as stasis, spherocytosis, increased mechanical fragility and possibly phagocytosis probably explain the increased cell destruction.

8. The occurrence of definite and sustained leukopenia with neutropenia and thrombocytopenia in several patients with hemolytic disease due to an immune body agent raises questions as to the etiology of classic thrombocytopenic purpura and of splenic neutropenia. Patients have been observed who seem to represent transition forms between acquired hemolytic anemia and thrombocytopenic purpura. Abnormal immune mechanisms could account for both excessive destruction of platelets and deficient formation.