Transfusion-induced immunologic unresponsiveness.
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Biomedical subjects
Publications and source records attributed to H A Perkins.
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A third Finnish En(a-) individual (ERP) with alloanti-Ena has been identified. Subsequent family studies revealed that ERP is distantly related to the 2 previous Finnish En(a-) propositi. Serologically, ERP's erythrocytes were found to be M-N-'N'+S-s+U+En(a-)Wr(a-b-) and were sialic acid deficient. SDS-PAGE studies confirmed that the red cell membranes lacked the MN-sialoglycoprotein, glycophorin-A. ERP's serum contained an IgG antibody which demonstrated two separable specificities, a ficin-sensitive specificity (anti-EnFS) and a ficin-resistant specificity (anti-EnFR), which reacted by the indirect antiglobulin technique. The antibodies were probably pregnancy induced, as ERP had never been transfused. A 51Cr-labelled red cell survival study showed that the antibodies were capable of causing significant destruction of incompatible red cells.
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Reported cases of acquired immunodeficiency syndrome (AIDS) in San Francisco as of March 31, 1986, include 92 individuals who had donated blood subsequent to 1978. Their donated blood components had been transfused into 406 different recipients. The current status of 336 of these recipients was ascertained as of April 1, 1986. Of these, 223 had died at the time of our first contact, almost all as a result of the condition for which they were transfused. Seven had developed AIDS; five of these died, two before entry into the study and three subsequently. Forty-six additional living recipients were interviewed and evaluated. Seven had the AIDS-related complex, 18 had antibody to the human immunodeficiency virus (HIV) but were otherwise healthy, and 19 had no detectable anti-HIV. Two had risk factors other than transfusion. The frequency of infection of the recipient decreased as the time interval between transfusion and the diagnosis of AIDS in the donor increased. This information should be useful when counseling patients who have been transfused with blood components from donors later found to be infected with HIV.
Acquired Immunodeficiency Disease (AIDS) may be transmitted by transfusion of blood components, although the risk remains extremely small. This report reviews the evidence for transmission by transfusion, the risk in several different situations, and the steps blood banks have taken to prevent transfusion of blood from donors at risk for AIDS. A test for the antibody to the virus responsible for AIDS (HTLV-III) will shortly be in routine use in blood banks, but the frequency with which the results will be falsely negative or falsely positive in a blood donor population remains to be established.
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A 52-yr-old multiparous white female was found to have Rh null blood type. She had macrocytic anemia, with reticulocytosis (15%-20%), of long duration. Although stomatocytes in peripheral blood were numerous and osmotic fragility was increased, suggesting increased cell water, the RBC cation content, and thus cell water, was decreased. Cell dehydration was confirmed by an increased proportion of high density RBC on Stractan density gradients. The deformability of RBC from four gradient subpopulations was measured in the ektacytometer as a function of suspending medium osmolality. Analysis of these measurements showed an abnormal reduction in cell surface area with increasing cell density, thus explaining the increased osmotic fragility of whole blood. This was confirmed by a density-dependent reduction in cell cholesterol content, suggesting membrane instability in vivo. Rh null subpopulations showed a twofold increase in both ouabain-sensitive and -insensitive Na-K ATPase activity and 86Rb transport, even in the dense fraction with the fewest reticulocytes. No membrane protein or glycoprotein abnormality was detected by SDS-PAGE. The associated deficiencies of both membrane surface area and cation content in Rh null cells, as well as increased Na-K pump activity, suggest a pleiotropic functional interrelationship among Rh antigen, membrane stability, and cation regulation.
An infant who received multiple transfusions during the first few days of life for rhesus disease became ill with recurrent infections when 6 months old. Hepatitis, thrush, Candida dermatitis, otitis media, and disseminated Mycobacterium avium intracellulare infection occurred by 14 months of age. Immunological studies showed raised immunoglobulin levels, decreased mononuclear-cell responses to allogeneic cells and mitogen, and a decreased helper/suppressor cell ratio. It was determined that one of the blood donors, who was well at the time of blood donation, had died 17 months after with multiple opportunistic infections and acquired immunodeficiency. The clinical and laboratory findings in our patient suggest that he acquired a transmissible infectious agent from a blood transfusion, resulting in acquired immunodeficiency, and that this agent was not cytomegalovirus, Epstein-Barr virus, or hepatitis B virus.
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Ten patients in a retrospective review of 250 kidney transplant recipients had RBC-cold agglutinins reactive at 22 C. Fourteen transplants were performed in those 10 patients. Five of nine cold renal allografts failed to function. Two of these recipients later had successful transplants when the kidneys were warmed before reestablishment of blood flow. Three other patients with cold RBC autoagglutinins had immediate renal function when the transplanted kidneys were warmed. In a prospective study of 126 patients, 59% had cold RBC agglutinins at 4 C and 11% were alos reactive at 22 C. Red blood cell-cold autoagglutinins appear to be a preventable cause of acute renal allograft failure. The titer and thermal amplitude of these antibodies are probably of major importance and should always be determined before organ transplantation.
This report presents the first prospectively followed case of hemolytic disease of the newborn due to anti-Jk3 alone. A Samoan woman with known anti-Jk3 was closely monitored during her third pregnancy. Because of elevated delta OD values in the amniotic fluid and rising titer of serum antibody, labor was induced at 36 weeks gestation. The cord red blood cells were coated with IgG, and anti-Jk3 was eluted from the cord cells and the placenta. A family study was done quantitating the expression of Kidd antigens by titrations and scores. Although titrations and scores have been reported to identify cells carrying the silent allele Jk in the heterozygous state, in this family, dosage differences were noted with only 1 of 2 Jk-heterozygous daughters.
In coagulation tests on five lowland gorillas, values within or close to the normal human range were found with the following tests: partial thromboplastin time, prothrombin time, thrombin time, factor XIII screen, factor II assay, factor V assay, fibrinogen and antithrombin III. Factor XII levels were very high. Factor VIII coagulant activity was moderately elevated but factor VIII antigen was very high in all and ristocetin cofactor activity was low in four of five.
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In this study, pretransplant transfusions significantly improved the survival of first cadaver kidney transplants. Large numbers of transfusions had the same influence on graft survival as small number of transfusions. Graft survival was not influenced by pretransplant antibody levels, and the beneficial effect of transfusions was also independent of highest pretransplant antibody levels. The positive relationship between transfusions and cytotoxic antibodies was shown to be highly significant. B-warm and T-warm antibodies were both increased by transfusions and tended to occur together. B-cold antibodies occurred independent of transfusions, B-warm and T-warm antibodies. The results of this study suggest, but do not confirm, that B-cold antibodies benefit graft survival, while T-warm antibodies adversely influence graft survival. Transfusions and B-cold antibodies appear to influence graft survival by different mechanisms.
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Two cases of Hansen disease demonstrating a lupus-like inhibitor directed against the activation of coagulation factor X are described. Each case showed factor-X activity markedly depressed by an inhibitor when measured in one assay system; yet normal levels were measured by three alternate factor-X assay systems.