Abnormal Hemolysis Research Articles

Infusion of marrow and spleen cells in irradiated NZB-Bl mice: amelioration of autoimmune disease.

Summary Adult NZB/Bl mice which showed a positive Coombs' test and other evidence of abnormal haemolysis were exposed to 800 r. whole body irradiation. They were then given an intravenous injection of bone marrow or a mixture of bone marrow and spleen cells from either young (Coombs negative) NZB/Bl mice or Coombs negative (NZB/Bl × T6) F1 hybrids.One of the 14 mice which received isogeneic cells died before being retested. Nine of the remaining 13 became Coombs negative; five of these remained negative and four reverted to Coombs positive 1–8 months after cell injection.Four of the II mice which received F1 cells died before being retested; six of the remaining seven became Coombs negative and remained so until they died or were killed 1–12 months after cell injection. Chromosome studies in the animal which survived longest in this group revealed that all dividing cells in the spleen and lymph nodes, and 90 per cent of the dividing cells in the bone marrow, were of donor origin.

A NEW CONGENITAL HEMOLYTIC ANEMIA WITH DEFORMED ERYTHROCYTES (? "STOMATOCYTES") AND REMARKABLE SUSCEPTIBILITY OF ERYTHROCYTES TO COLD HEMOLYSIS IN VITRO

A new variant of congenital hemolytic anemia is described. The principal clinical findings are moderately severe hemolytic anemia, jaundice, and splenomegaly; congenital ptosis of an eyelid may possibly be an associated anomaly. Splenectomy resulted in clinical improvement but did not completely arrest abnormal hemolysis nor alter red cell abnormalities. Laboratory data are presented which characterize the condition; the principal abnormalities detected thus far are: (1) abnormal morphology of the erythrocytes ("stomatocytes"); ) increased osmotic fragility and autohemolysis; (3) storage instability greater at 5°C than at 37°C; (4) decreased concentration of reduced glutathione despite normal G-6-P-D and G-6-P-D coupled glutathione reductase activities. The disorder is compared with hereditary spherocytosis and hereditary stomatocytosis; similarities to and differences from these disorders are reviewed.

Radioactive Iron Studies in Patients with Iron Deficiency Anemia with Concurrent Abnormal Hemolysis

Abstract A report is presented on two women suffering from severe iron deficiency anemia, concomitant with abnormal hemolysis. The life span of the patients’ red cells was shortened; transfused normal red cells were more rapidly broken down. Extracorpuscular factors seem to be responsible for the pathologic hemolysis. There was no pathologic sequestration of red cells labeled with Cr51 in the spleen. After incorporation of radioactive iron into the red cells, the utilization percentage of Fe59 under iron therapy fell to about 15 per cent within a few weeks. This, too, indicates that the pathologic hemolysis was to be ascribed to extracorpuscular factors. The Fe59 was apparently not sufficiently reutilized. The constantly decreased serum iron concentration might also indicate a disturbance in the reutilization of iron liberated during red cell breakdown. Six other patients with less severe iron deficiency anemia and an insufficient response to iron therapy were examined in addition. In 5 of these patients, the life span of red cells labeled with radioactive chromium was found shorter than normal. An insufficient response to iron therapy in patients with chronic iron deficiency anemia may be ascribable, in some instances, to concomitant pathologic hemolysis.

The Auto-Immune Hemolytic Anemia of Malignant Lymphocytic Disease

Abstract Twenty-four cases of malignant lymphocytic disease associated with frank hemolytic anemia are reviewed. Four cases were associated with some form of lymphosarcoma and twenty cases appeared in conjunction with chronic lymphocytic leukemia. In the latter cases, the hemolytic process was detected in eleven patients from one-half to five years after the original diagnosis had been established. In three patients, a positive Coombs’ test antedated the development of any other evidence of a hemolytic process by either several months or a year. In a significant number of cases, x-ray therapy seemed to precipitate the appearance of the abnormal hemolysis. In nine other patients, only when symptoms referable to hemolytic anemia necessitated medical aid, was the lymphocytic leukemia detected. Of the four patients with lymphosarcoma, three presented themselves initially as cases of hemolytic anemia. The primary diagnosis was uncovered only after lymph node biopsy or laparotomy. The physical examination in both disease groups represented a combination of the findings associated with hemolytic anemia and lymphocytic disease. In the cases of chronic lymphocytic leukemia, this led to splenomegaly of unusual degree and disproportionate to the size of the lymphadenopathy. The laboratory findings likewise combined the features of both the primary lymphocytic disorder and hemolytic anemia. Anemia, reticulocytosis, spherocytosis, and bilirubinemia of the indirect type were present, and in the cases of lymphocytic leukemia, elevated white cell counts with diminished platelet counts were found. The bone marrow in many instances represented a "duality of proliferation", hyperplasia of erythroid and lymphoid elements existing side by side. Immunologic studies clearly indicated that the mechanism of hemolysis in these cases differed in no respect from that of "idiopathic" auto-immune hemolytic anemia. The direct Coombs’ test was positive in all twenty cases in which it was employed, and circulating hemagglutinins were demonstrated in eleven of nineteen cases so tested. The multiplicity of laboratory indications of hemolysis, as well as the distinct immunologic mechanism, distinguish these cases of hemolysis from the so-called "occult" hemolytic anemia. The term "overt" hemolytic anemia has been used to emphasize the difference. The role of the lymphoid apparatus in the production of such auto-immune hemolytic anemia is discussed. The bulk of evidence would seem to implicate some cellular component of the lymphoid system, although not the adult lymphocyte, as the producer of antibody. The architectural disruption of this system in malignant lymphocytic disease might well have a functional counterpart with respect to its immunologic duty. The resultant aberration may manifest itself clinically as auto-immune hemolytic anemia. At present the therapy of choice for control of the hemolytic process is ACTH, Compound E or Compound F. Transfusions and splenectomy are useful ancillary measures when hormonal therapy is either partially or totally unsuccessful. The hemolytic component should be treated independently of the lymphocytic proliferation since control of both cannot be established by any one agent currently available.