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Biomedical subjects

G Garratty

Publications and source records attributed to G Garratty.

At least 163 records · Page 9Linked to original sources

A clinically significant erythrocyte antibody detectable only by 51Cr survival studies.

Hemolytic transfusion reactions typically are explained by red cell serologic incompatibilities. We describe a patient in whom a clinically significant red cell alloantibody could not be demonstrated, despite the occurrence of several clinically severe hemolytic reactions. Serologic studies using multiple techniques demonstrated only an anti-Bga; these studies included standard procedures as well as more sensitive experimental techniques. A 51Cr survival study using red cells from a random unit, compatible in vitro with conventional techniques, showed 72 percent survival at 1 hour and 7 percent survival at 24 hours. R2R2 (hr" (e) negative) red cells in a second 51Cr survival study showed 90 percent survival at 1 hour and 92 percent survival at 6 hours. The patient was transfused with R2R2 units which were tolerated well and survived normally. Extensive serologic testing still demonstrated only an anti-Bga. A third 51Cr survival study, 10 months after the first study, with an R1R1 (hr" (e) positive) sample showed 90 percent survival at 1 hour and 42 percent survival at 6 hours. A fourth study using a larger aliquot of R2R2 (hr"(e)negative) 51Cr-labeled red cells, examined over 2 weeks showed a near normal 21-day survival of 50 percent. These 51Cr survival studies, along with normal survival of hr" (e) negative units, suggest that this patient destroys hr" (e) positive red cells despite negative serologic testing.

Anemia, Hemolytic↗

Depressed blood group antigens on red cells from a Mexican donor.

Red cells from a Mexican blood donor had depressed H, IF, ID, i, Sda, Sdx, D, LW, Dib, Vel and JMH antigens. A wide range of other blood group antigens had normal activity. The unusual red cell phenotype may be caused by a membrane anomaly that alters orientation of certain cell surface components. The specificities of the depressed red cell antigens in this phenomenon differ from those affected in Melanesians with ovalocytosis or in individuals with the In(Lu) inhibitor gene.

ABO Blood-Group System↗

Standardization of IgG subclass antiserums for use with sensitized red cells.

The only IgG subclass antiserums standardized for use with red cells are those sold by the Netherlands Red Cross. Their recommended method is a sedimentation antiglobulin test (AGT) not generally used in the USA. Some years ago we tested the antiserums for sensitivity and specificity using the routine centrifugation AGT and found the methods comparable. More recently, we have become concerned since the antiserums are being used by a variety of methods other than the recommended procedure. It is well-known that it is difficult to prepare subclass antiserums without contaminating antibodies to other IgG markers. Thus, we thought it worthwhile to standardize the antiserums with particular emphasis on specificity using several different technics. We found that some methods that have been used to define the subclass of red cell-bound IgG were inappropriate, and led to many false positive results.

Antibody Specificity↗

Acute hemolytic anemia associated with a chlorpropamide-induced apparent auto-anti-Jka.

A patient with acute hemolytic anemia and a positive direct antiglobulin test was found to be Jk(a + b +) with anti-Jka in her serum. For 2 weeks prior to admission, the patient had taken chlorpropamide, a hypoglycemic agent. The drug was discontinued upon the diagnosis of hemolytic anemia, and the hemoglobin concentration gradually increased. When chlorpropamide was added to the patient's serum in vitro, it enhanced the reactivity of the anti-Jka, and 40 days posttransfusion, the serum would only react with Jk(a+) red cells when chlorpropamide was present. These findings suggest that a chlorpropamide-dependent antibody with Jka specificity had formed. We do not know why the antibody induced by chlorpropamide reacted preferentially with Jk(a+) red cells.

Acute Disease↗

Spontaneous agglutination of red cells with a positive direct antiglobulin test in various media.

Red cells from 475 individuals (donors and patients) with a positive direct antiglobulin test (DAT) (66% were 1/2+ to 1+, 19% were 1 1/2+ to 2+, and 15% were 2 1/2+ or greater) were examined for spontaneous agglutination following incubation in various media. Twenty-three percent of the samples showed spontaneous agglutination in commercial Rh control solutions, 6 percent in 30 percent albumin, 3 percent in 10 percent albumin, 2 percent in 6 percent albumin, and 1 percent in saline. Cells suspended in serum were more prone to spontaneous agglutination. The strength of spontaneous agglutination varied; more than 50 percent of the samples reacted only 1+ or less, approximately 10 percent reacted 2+ or stronger. There was not a complete correlation with spontaneous agglutination and quantity of IgG on the cells, as determined by the antiglobulin test. Of those samples showing spontaneous agglutination, 50 percent were associated with a DAT strength of more than 2+, 27 percent with a DAT of 1 1/2+ to 2+, and 23 percent with a DAT of 1/2+ to 1+. Spontaneous agglutination occurred with the same frequency whether the cells were sensitized with both IgG and C3 or with IgG alone. Surprisingly, 7 percent of the samples sensitized with C3 but no detectable IgG also demonstrated spontaneous agglutination. Marked differences in reaction strength were seen with Rh control solutions from different manufacturers, and the degree of spontaneous agglutination was inconsistent with individual products.

ABO Blood-Group System↗

Predicting the clinical significance of red cell alloantibodies using a monocyte monolayer assay.

Few data have been published that correlate in vitro monocyte monolayer assays (MMA) and red cell (RBC) survival in patients with alloantibodies of unknown significance. Over the past 6 years we gathered clinical correlations in 12 patients with the following antibodies: anti-Lan (three patients), -Ge (three patients), -Yta (five patients), and -Ytb (one patient). RBC survival was estimated using 51Cr studies in seven patients and follow-up of transfusion of incompatible blood in the other five. Six patients with no evidence of RBC destruction had negative MMA findings (anti-Lan [one patient], -Ge [two patients], and -Yta [three patients]). Five patients with evidence of in vivo RBC destruction had significant MMA results. The two clinically significant anti-Lans required fresh serum to give a meaningful MMA result. One patient (anti-Ytb) had an MMA result of borderline significance--normal 51Cr RBC survival at 1 hour--but a reduced T50Cr. The MMA we used appeared to predict the clinical outcome of transfusion in every patient with antibodies to high-frequency antigens whom we tested.

Erythrocyte Aging↗

A severe transfusion reaction associated with anti-EnaTS in a patient with an abnormal alpha-like red cell sialoglycoprotein.

A 71-year-old woman (Ped) received 3 units of red cells (RBCs), compatible by the indirect antiglobulin test but strongly (4+) incompatible by direct agglutination at 37 degrees C. The next day, her plasma hemoglobin was 1252 mg percent and the direct antiglobulin test (DAT) was weakly positive (IgG and C3). Less than 5 percent of the transfused cells could be detected 48 hours posttransfusion. Her clinical condition deteriorated and renal failure developed. The patient died of pulmonary embolism. Her serum contained a strong (4+) IgM agglutinin and a weakly reactive (microscopically positive) IgG antibody, with anti-EnaTS specificity. EnaFS and EnaTS antigens were severely depressed or absent from the patient's RBCs; the ficin-resistant Ena antigen (EnaFR) appeared to be present. Pretransfusion RBC sialic acid level was 53 +/- 2 percent of normal. The patient's RBC membranes were shown to contain sialoglycoproteins beta and delta by sodium dodecyl sulphate polyacrylamide gel electrophoresis with periodic acid Schiff's base staining, with weak staining of components in the regions corresponding to alpha, alpha 2 and alpha delta. The nature of these components was not identified, but their presence suggested that the patient's RBCs expressed a previously undescribed sialoglycoprotein alpha variant.

Aged↗

Evaluation of the optimal incubation temperature for detecting certain IgG antibodies with potential clinical significance.

It is commonly believed that IgG antibodies react optimally at 37 degrees C, but there are few published data supporting this. In this study, 140 antibodies from the Rh, Kell, Duffy, Kidd, and SsU blood groups were studied by a low-ionic-strength solution indirect antiglobulin technique at four different temperatures of incubation: 10, 22, 30, and 37 degrees C. Only titration score differences of greater than 10 were considered significant. None of the 140 antibodies sensitized red cells (RBC) significantly better at 10, 22, or 30 than at 37 degrees C. All antibodies, except one example of anti-c, sensitized RBCs as well at 30 as at 37 degrees C. At 22 degrees C, 100 percent of Kidd and SsU, 94 percent of Kell, and 82 percent of Duffy, but only 49 percent of Rh antibodies sensitized RBCs as well as they did at 37 degrees C. It is possible that these differences reflect the influence of antigenic structures and/or topography on the thermal dynamics of the antigen-antibody bond.

Autoanalysis↗

Clinical significance of anti-Yt(b). Report of a case using a 51chromium red cell survival study.

Several published reports have documented the variable survival of Yt(a+) red cells (RBC) in patients with anti-Yt(a) as measured by 51Chromium (Cr)-labeled RBC survival studies. Similar studies with anti-Yt(b) have not been reported. A 51Cr-labeled RBC survival study was performed using Yt(b+) RBCs and a monocyte monolayer assay in a young hemodialysis patient who required chronic transfusion therapy and who had developed anti-Yt(b). The survival of the transfused RBCs was 100 and 93 percent at 1 and 24 hours, respectively, with a half life of 21 days at termination of the study (normal, 28 to 32 days). These results showed no evidence of rapid destruction of the Yt(b+) RBCs, indicating that this patient could be transfused safely with blood from Yt(b+) donors. Long-term survival of the 51Cr-labeled Yt(b+) RBCs was shortened moderately, however, a finding that correlated with a slightly abnormal monocyte monolayer assay test.

Adult↗

Determination of zygosity using flow cytometric analysis of red cell antigen strength.

A flow cytometry method, developed in our laboratory to measure red cell (RBC)-bound IgG, was compared to the manual titration technique in the measurement of RBC antigen strength to determine zygosity. Parallel studies using antibodies to antigens in the Rh, Kell, Kidd, Ss, and Duffy systems were performed. The antisera (n = 20) were tested against five examples each of RBCs from apparent homozygotes and heterozygotes. The flow cytometry method was clearly superior, showing distinct differences, with no overlap of the ranges of results, between the reactions of RBCs from homozygotes and heterozygotes with 10 of 20 (50%) antisera. By the manual titration technique none of these sera clearly demonstrated dosage and 15 showed overlap of the ranges. It was obvious from the results that the commonly used manual titration technique for comparing the test RBCs with a single example of RBCs from a homozygote and heterozygote yielded inaccurate results.

Blood Group Antigens↗

Cefotaxime-induced immune hemolytic anemia due to antibodies reacting in vitro by more than one mechanism.

Until recently, all cephalosporin-induced immune hemolytic anemias appeared to react by a "penicillin-type" drug adsorption mechanism, and hemolysis was extravascular. In 1987 and 1988, the first two cases of cephalosporin-induced immune hemolytic anemia with intravascular hemolysis associated with a so-called immune complex mechanism were reported. This report describes a case of extravascular hemolysis due to a third-generation cephalosporin, cefotaxime, which, to the authors' knowledge, is the first to show in vitro characteristics of both the drug adsorption and the so-called immune complex mechanisms.

Adult↗

Fatal immune hemolytic anemia due to cefotetan.

In the first death associated with immune hemolytic anemia due to cefotetan, the patient developed hemolytic anemia and renal failure, dying 12 days after the beginning of 1 week's cefotetan therapy. The patient's serum contained strong antibodies reacting with cefotetan-treated red cells (RBCs) and with uncoated RBCs in the presence of cefotetan; a much weaker, drug-independent antibody was also detected. Three-days before the patient's death, the antibody reacting with cefotetan-coated RBCs rose to a titer of 262,144; the titer of the antibody to uncoated RBCs, in the presence of cefotetan, rose to 2048; the titer of the drug-independent antibody remained at 4.

Anemia, Hemolytic, Autoimmune↗