Cold Hemagglutination in Acute and Chronic Hemolytic Syndromes

1. Three cases have been described of hemolytic anemia associated with autoagglutination of erythrocytes in the cold. These cases were characterized clinically by pallor, slight icterus and lack of splenomegaly. Raynaud’s phenomenon was present in two of the three patients. The first patient had an acute self-limited course. The second and possibly the third were chronic and apparently persistent.

2. A hemolysin was demonstrated in the chronic variety of hemolytic anemia. This antibody was active at body temperature, required complement and appeared to be independent of the cold agglutinin. It disappeared following therapy with cortisone. In the third case, hemolysin was demonstrated directly attached to the surface of the patient’s erythrocytes by the addition of complement to the washed red cells. The hemolytic reaction was enhanced by the use of trypsinized test erythrocytes.

3. "Complete and incomplete" cold agglutinins were demonstrated by the use of saline, albumin and trypsin technics as well as by the Coombs’ antiglobulin reactions. Erythrocyte coating antibodies were not neutralized with human gamma globulin. Cold agglutinins and erythrocyte coating antibodies were unaffected by cortisone therapy.

4. Survival of transfused erythrocytes was increased in one patient during the period of cortisone treatment, despite the fact that cold agglutinins persisted.

5. Cold agglutinated erythrocytes have increased mechanical fragility when the cold agglutinin is present in high titer. Incubation at 37 C. for 24 hours causes a marked shift to the left in the osmotic fragility curve.

6. Study of the serum in one patient for antibodies to Newcastle virus disease and influenza failed to disclose these antibodies in significant titer.