Platelet transfusion therapy; the selection of compatible platelet donors for refractory patients by lymphocyte HL-A typing.
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Biomedical subjects
Publications and source records attributed to F C Grumet.
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Three high frequency reactive antisera (Kir, Oca, Mil) are described which, based on serologic and genetic characteristics, identify a set of apparently related antigens. The antibodies react only by indirect antiglobulin technique against both adult and cord red blood cells, are primarily IgG, are not complement dependent nor enhanced by papain pretreatment of red blood cells, are high titered but of low avidity, and are not neutralized by serum nor absorbed by platelets. The antisera are not identical with, but may be related to, the Kna antibody. Population data show reactivity frequencies of 99.8 per cent for Kir, 98.7 per cent for Oca, and 96.4 per cent for Mil. The four phenotypes found are Kir+, Oca+, Mil+; Kir+, Oca+, Mil- Kir+, Oca-, Mil+ and Kir-, Oca-, Mil-. The occurrence of five unrelated triple negative individuals is greater than would be expected by chance alone for three independent antigens. Family studies demonstrate that the triple negative phenotype appears to be a recessive trait not linked to the Fy or MNS loci, and the Mil-trait is not linked to ABO, Jk, or HLA. Clinical observations following infusion of incompatible blood and in vivo survival studies of 51Cr tagged red blood cells indicate that the antigens, though potent immunogens, are not clinically significant.
In patients with severe allergic reactions to plasma proteins it is possible to observe such reactions to even the small quantity of plasma contained in platelet concentrates. A platelet washing solution was designed, and platelet concentrates for four such patients were washed before infusion. Transfusion reactions were completely eliminated by the washing procedure. Platelet recovery was equivalent to that of unwashed platelets, and hemostatic effectiveness of the infused platelet concentrates was evidenced by abrupt cessation of bleeding episodes, including purpura and hematuria. Platelet washing represents a valuable, rapid and simple approach to the problem patient with thrombocytopenia and severe reactions to plasma proteins.
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A simple technique for red blood cell typing is described utilizing V-bottom microtiter trays with cell suspensions of 0.2%. This technique is many times more sensitive than tube or slide methods and can be used for direct agglutination, antiglobulin tests and mixed field agglutination.
Nonhemolytic, IgG, anti-IT autoantibodies were found in the sera of three Caucasian patients, none of whom had Hodgkin's disease. Each antibody reacted by indirect antiglobulin test. Two of the three also reacted in albumin at 37 C, and one of these was moderately enhanced by papain. As judged by transfusion responses, reticulocyte counts, hematocrit stability, and one hour 51Cr red blood cell survivals, none of the antibodies were considered to be hemolytic. When tested with anti-IgG serum, cells from all three had a positive direct antiglobulin test. Anti-IT antibody was eluted from their cells. Ii status of the patients' cells differed from normal in each case. These data suggest greater variation in the disease association, serologic reactivity, and clinical significance, of anti-IT than has been evident from previous studies.
A new antibody, anti-Rh41, is described. This antibody was found prepartum in a multiparous, Caucasian female with no prior history of transfusions. Anti-Rh41 reacts with red blood cells from individuals with cis oriented C and e genes, but is nonreactive with cells possessing the products derived from individuals with cis-oriented Cw and e genes, a characteristic which distinguishes this antibody from anti-rhi. Furthermore, in contrast to anti-rhi, anti-Rh41 consistently reacts with Negro rh's (VS-positive) bloods. Also noteworthy in this study is the presence of an abnormal expression of chromosome 1 genetic markers in an offspring of the propositus.
The need for anti-complement (anti-C') activity in antiglobulin antisera (AHG) for the detection of clinically significant antibodies was evaluated during a three-year period. While performing routine compatibility testing using standard blood banking procedures, eight patients were found whose antibodies were detectable primarily or only by AHG containing anti-C' activity; monospecific anti-igG AHG gave weak or negative reactions. Seven of the antibodies were anti-jka or jkb. Two of the anti-jka antibodies were responsible for clinically unsuspected delayed hemolytic transfusion reactions. The anti-jkb antibody resulted in a shortened survival of incompatible 51Cr-labelled red blood cells. The incidence of such "complement-only" Kidd antibodies was 23 percent of all Kidd antibodies found. These data suggest that the omission of anti-C' in AHG in routine compatability testing could result in substantial risk of failure to detect clinically significant antibodies.
Using a recently developed enzyme-linked immunosorbent assay, gene dosage effects were demonstrated for the Duffy, Ss, and Rh red blood cell antigen systems. We report a comparison by an antibody-binding assay of the relative amounts of Fya and Fyb antigens on FyaFya, FyaFyb, FybFyb, FyaFyx, and FyxFyx erthrocytes, and of s antigen on cells homozygous and heterozygous for s. The immunosorbent assay also was used to study Rh antigens, and data which had been obtained using radiolabelled antibodies were confirmed.
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In light of increasing public and employee concern over potential infectious hazards associated with blood and other body fluids, several government agencies (the Food and Drug Administration, the Centers for Disease Control, the Occupational Safety and Health Administration, the Environmental Protection Agency, the Health Care Financing Administration and the National Heart, Lung and Blood Institute) cosponsored a Biosafety Workshop in April 1988. The objective of the workshop was to identify appropriate biosafety practices and standard control procedures to protect workers involved in the collection, storage, and transportation of human blood donations with the least possible disruption of the nation's blood supply. Speakers focused on human immunodeficiency virus (HIV) and hepatitis B virus (HBV); however, the safety principles discussed were considered equally applicable to other known (e.g., non-A, non-B hepatitis and human T-lymphotropic virus type I (HTLV-1) blood-transmitted infections. The resulting consensus included the need for blood establishments to develop and apply thoughtful biosafety programs to address staff training, accident prevention, HBV vaccination, handling spills, managing contaminated waste and transporting blood specimens. There was lack of agreement, however, on the usefulness of gloves during the phlebotomy of healthy blood donors.
The identification of HLA class I alloantibodies is important for organ transplantation and platelet transfusion in alloimmunized patients. Because microcytotoxicity testing against frozen trays of lymphocyte panels is rapid and efficient for determining specificities of unknown antibodies, a simple method was devised to increase test sensitivity to weak antibodies. Standard anti-human globulin (AHG)-facilitated microcytotoxicity was modified by the insertion of a double addition-of-serum (DAS) step, and reagent and patient's sera were evaluated by both methods. DAS modification increased antibody titers and, more significantly, made the identification of weak specificities easier because of the twofold to threefold increase in reactivity rates (29-42% for AHG vs. 75-82% for DAS) of panel cells that were expected to be positive, while low (approx. 1%) "extra" reaction rates were maintained for cells that were expected to be negative. DAS was relatively unaffected by variations in serum volumes or target cell preparation, and its use did not significantly increase test time or costs. In a program of platelet donor selection driven by donor antibody rather than donor-recipient antigen matching, DAS greatly facilitated platelet transfusion support for alloimmunized patients.
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