Iso-leukoagglutinins are known to develop primarily in multitransfused patients (1-6). A possibly different kind of agglutinin for white cells, such as that related to aminopyrine leukopenia, has also been described (7). The therapeutic administration of blood and of aminopyrine may not be the only stimuli for leukoagglutinin production. Two groups of investigators, Dausset, Nenna and Brecy (8) and Whyte and Yee (9), have drawn upon the analogy to Rh antibody formation, and have discussed the possibility that fetal leukocyte antigens might act as stimuli to the mother. Killman (10) considered this potential source of antigen in his investigations of leukoagglutinins in collagen diseases, but he was unable to find any correlation between pregnancies and leukoagglutinin formation. The studies presented in this paper demonstrate that fetomaternal leukocyte incompatibility may induce leukoagglutinin formation in the mother, and suggest that some leukocyte factors, as demonstrated by their corresponding leukoagglutinins, may be genetically transmitted to the offspring. METHODSTechnique of the test for leukoagglutinins. The details of the test for leukoagglutinins were presented in previous publications (2, 3). In this study, the test leukocytes for iso-leukoagglutinins were obtained from 10 persons of red cell blood group 0; these were healthy donors whose red cells differed in their Rh factors. All inactivated sera were tested against the entire panel of 10 leukocyte donors. A leukoagglutinin test was considered positive when different samples of serum obtained from the same individual produced compact clumping of the leukocytes of a panel member on two different occasions. The sera selected as positive in this series were those which produced clumping of two or more members of the leukocyte panel. Weakly reacting sera were occasionally observed. These induced very weak clump-' This study was supported by Research Grant H-3365, National Institutes of Health, United States Public Health Service.2 Presented before the Western Society for Clinical Research, Carmel, Calif., Jan. 30 through Feb. 1, 1958. ing, or only agglutinated one member of the leukocyte panel. They were arbitrarily not included among the positive sera. Some of the weak reactions could be attributed to the adherence of leukocytes to noncellular material in serum; others seemed to be related to the gradual deterioration of the test leukocytes with time. In order to minimize these sources of error, fresh leukocytes were obtained daily. Different members of the leukocyte panel reacted with a single test serum so as to give titer differences no greater than those inherent in the serial dilution method of titration. The patients' own leukocytes were employed in tests for autoleukoagglutinins. When red cell antibodies other than anti-A or anti-B were present in test sera the test leukocytes were selected so that the accompanying red blood cells would not contain the conflicting factors. In family studies, in which sera from persons of one ABO blood gro...

Iso-leukoagglutinins are known to develop primarily in multitransfused patients (1-6). A possibly different kind of agglutinin for white cells, such as that related to aminopyrine leukopenia, has also been described (7). The therapeutic administration of blood and of aminopyrine may not be the only stimuli for leukoagglutinin production. Two groups of investigators, Dausset, Nenna and Brecy (8) and Whyte and Yee (9), have drawn upon the analogy to Rh antibody formation, and have discussed the possibility that fetal leukocyte antigens might act as stimuli to the mother. Killman (10) considered this potential source of antigen in his investigations of leukoagglutinins in collagen diseases, but he was unable to find any correlation between pregnancies and leukoagglutinin formation. The studies presented in this paper demonstrate that fetomaternal leukocyte incompatibility may induce leukoagglutinin formation in the mother, and suggest that some leukocyte factors, as demonstrated by their corresponding leukoagglutinins, may be genetically transmitted to the offspring. METHODSTechnique of the test for leukoagglutinins. The details of the test for leukoagglutinins were presented in previous publications (2, 3). In this study, the test leukocytes for iso-leukoagglutinins were obtained from 10 persons of red cell blood group 0; these were healthy donors whose red cells differed in their Rh factors. All inactivated sera were tested against the entire panel of 10 leukocyte donors. A leukoagglutinin test was considered positive when different samples of serum obtained from the same individual produced compact clumping of the leukocytes of a panel member on two different occasions. The sera selected as positive in this series were those which produced clumping of two or more members of the leukocyte panel. Weakly reacting sera were occasionally observed. These induced very weak clump-' This study was supported by Research Grant H-3365, National Institutes of Health, United States Public Health Service.2 Presented before the Western Society for Clinical Research, Carmel, Calif., Jan. 30 through Feb. 1, 1958. ing, or only agglutinated one member of the leukocyte panel. They were arbitrarily not included among the positive sera. Some of the weak reactions could be attributed to the adherence of leukocytes to noncellular material in serum; others seemed to be related to the gradual deterioration of the test leukocytes with time. In order to minimize these sources of error, fresh leukocytes were obtained daily. Different members of the leukocyte panel reacted with a single test serum so as to give titer differences no greater than those inherent in the serial dilution method of titration. The patients' own leukocytes were employed in tests for autoleukoagglutinins. When red cell antibodies other than anti-A or anti-B were present in test sera the test leukocytes were selected so that the accompanying red blood cells would not contain the conflicting factors. In family studies, in which sera from persons of one ABO blood gro...

No abstract

Low molecular weight (40,000) dextran is being extensively used in open heart surgery to minimize the amount of donor blood required and to inhibit red cell aggregation. At equal concentrations, its effects on blood coagulation were less than those of standard dextran plasma substitutes; but in the very high concentrations used in open heart surgery its effects were greater. Addition of low molecular weight dextran to normal plasma caused a gross precipitate and striking inhibition of coagulation. Factor VIII (antihemophilic factor) and fibrinogen were partially removed with the precipitate. Patients subjected to open heart surgery had lower levels of these two clotting factors in their plasma when dextran was used, but it is not certain whether this loss occurred in vivo, or during separation of the plasma from red cells (and precipitate) prior to testing. No proof was obtained in this series of cases that low molecular weight dextran increased the tendency to bleed, but the results indicate that this would be a likely possibility with the use of larger amounts. The low molecular weight dextran had a slight tendency to induce red cell aggregation by itself. It potentiated the aggregative effect of Polybrene and the agglutinating effect of a saline Rh antibody. On the other hand, it inhibited agglutination of red cells induced by an Rh antibody in a high protein medium. It thus appears likely that high concentrations of low molecular weight dextran in the blood of a patient could lead to erroneous conclusions in compatibility tests.

Measurement of ionized calcium levels by the technic of Soulier during massive transfusion of ACD blood supplemented with various quantities of calcium led to the apparently erroneous conclusion that ionized calcium levels would rise in the recipient when each unit was supplemented with 0.6 g CaCl2, the quantity which restores normal ionized calcium levels in vitro. Measurement of ionized calcium activity with the Orion electrode indicates that this ratio of CaCl2 will maintain an approximately normal ionized calcium level in dog recipients if it is infused simultaneously with the blood. Based on this information, it appears reasonable to assume that heparinized ACD blood, recalcified with 0.6 g CaCl2 per unit, may be used to prime the extracorporeal circuit for open heart surgery with the confidence that it will not alter the ionized calcium activity of the patient's blood. Addition of calcium to the circulation following administration of ACD blood causes a sharp rise and then a fall in the recipient's level of ionized calcium. Further studies in a variety of situations are required before final guidelines can be formulated for supplementation of ACD blood with calcium in massive transfusion.