The Mechanism of Hemolysis in Paroxysmal Cold Hemoglobinuria

Abstract

Abstract Attacks of hemoglobinemia were induced in 2 patients with paroxysmal cold hemoglobinuria (PCH). The occurrence of slight neutropenia and erythrophagocytosis in the first patient occasioned more detailed observations of these phenomena in the second. The in vivo changes observed in Case 2 following three episodes of chilling were similar to those described by earlier investigators. Marked hemoglobinemia and hemoglobinuria occurred twice; mild hemoglobinemia once. The maximum number of phagocytes was observed at the time of maximum hemolysis. Leukopenia developed promptly during each attack, but the degree of leukopenia was not correlated with either the intensity of erythrocyte destruction or with the extent of phagocytosis. Neutrophils and monocytes—the phagocytic cells—and eosinophiles were equal1y depressed, all decreasing by from 75 per cent to 80 per cent. Lymphocytes decreased by 33 per cent to 48 per cent. The neutrophils recovered within 2 hours, but the eosinophiles and lymphocytes remained depressed for 5 hours. When PCH serum was chilled and warmed with complement and homologous or heterologous erythrocytes and leukocytes, erythrophagocytosis occurred, reaching its maximum at a time consistent with the development of leukopenia in vivo. Although PCH antibody was fixed to erythrocytes in the cold phase of the Donath-Landsteiner reaction, phagocytosis did not occur if complement, with the attending hemolysis, was absent in the warm phase. Erythrophagocytosis was also produced in vitro when human isoantibodies acted as either agglutinins or hemolysins. Phagocytosis was most marked when the sensitized cells were lyzed, the degree of phagocytosis corresponding to the degree of hemolysis. The in vivo and in vitro observations suggest that leukopenia occurs in persons with cold hemoglobinuria as part of the paroxysm of hemolysis, and that erythrophagocytosis operates to remove damaged erythrocytes and probably promotes the trapping of leukocytes in organ capillaries.