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Biomedical subjects

G Garratty

Publications and source records attributed to G Garratty.

At least 19 recordsLinked to original sources
PubMed1992

Selection of platelets for refractory patients by HLA matching and prospective crossmatching.

A multi-site clinical study compared platelets chosen for refractory patients by prospective platelet crossmatching using stored donor platelets and HLA-based selection. Seventy-three patients who were refractory to random-donor platelets received two plateletpheresis components, one chosen by HLA-based criteria and the other by crossmatching. Patients were carefully evaluated to exclude nonimmune factors that could adversely affect transfusion results. Each of the five study sites used a crossmatch procedure with which it had experience. Results from this study indicate the following: 1) The overall rate of successful transfusion was similar when an HLA-based method of donor selection that includes all grades of matching and mismatching was compared to a crossmatch-based method of donor selection. 2) HLA-based selection that restricts recipients to grade A and BU matches was superior to a selection method based upon crossmatching alone. Donor selection based on HLA matching (grades A or BU) was also superior to selection based on any degree of HLA mismatching (grades BX, C, or D). 3) Selection of donors based on HLA-cross-reactive groups (defined by in vitro serologic crossreactivity) was no more successful than that based on grade C and D mismatches and was no more successful than selection by crossmatching alone. 4) Lymphocytotoxic and platelet antibodies were not detected in many of the enrolled patients, even though patients demonstrating nonimmune factors were eliminated from the study. It can be concluded that HLA-compatible (grades A and BU) platelets provide optimal support for refractory patients, but that crossmatch-selected platelets are acceptable as an alternative component.

Adult↗
PubMed1991

A fatal case of ceftriaxone (Rocephin)-induced hemolytic anemia associated with intravascular immune hemolysis.

Fatal hemolytic anemia developed in a 52-year-old woman who was treated with a cephalosporin, ceftriaxone. The patient's red cells (RBCs) were coated with C3, but no RBC-bound IgG, IgA, or IgM was detected. Her serum contained an antibody that did not react with cephalosporin-coated RBCs but reacted strongly with RBCs in vitro when her serum was added to drug and RBCs. This is the first case of immune hemolytic anemia associated with ceftriaxone, the first case of fatal cephalosporin-induced hemolytic anemia, and the second case in which a cephalosporin antibody showed in vitro and in vivo characteristics usually thought to be associated with the so-called immune complex mechanism.

Anemia, Hemolytic↗
PubMed1991

Effect of cell-bound proteins on the in vivo survival of circulating blood cells.

Normal circulating red blood cells (RBCs) and platelets have been shown to have small amounts of IgG on their membranes. The cell-bound IgG may be cytophilic (IgG nonspecifically adsorbed from the plasma) and/or IgG autoantibody. It has been suggested that most of the RBC-bound IgG is on older RBCs and is an autoantibody directed against senescent cell antigen (SCA). The accumulation of this RBC-bound IgG leads to Fc-dependent removal of senescent RBCs by macrophages in the reticuloendothelial system. RBCs also have complement components on their membrane; it is not clear how this accumulates on RBCs and whether it has a physiologic function. This small amount of nonpathogenic RBC-bound IgG is not detected by the antiglobulin test. It is still unclear whether the major difference between pathogenic and nonpathogenic IgG autoantibodies is qualitative, quantitative, or both. Seemingly healthy blood donors (1 in 1,000 donors) and patients without hemolytic anemia (up to 8% of patients) have increased amounts (greater than 200 molecules/RBC) of RBC-bound IgG and complement that is detected by the antiglobulin test. This RBC-bound IgG has been shown to be an IgG autoantibody directed against blood group antigens, and/or IgG anti-idiotype, and/or IgG nonspecifically adsorbed onto the RBC membrane when plasma IgG levels are high. Most patients with autoimmune hemolytic anemia (AIHA) have RBC-bound IgG and/or complement detectable by the antiglobulin test. Most of the RBC-bound IgG is of the IgG1 subclass, whether one examines the RBCs of healthy blood donors or hospitalized patients with and without AIHA. Although the quantity of RBC-bound IgG is generally higher in patients with AIHA, there is no clear correlation with the quantity of RBC-bound IgG and the rate of in vivo RBC destruction. There is some recent evidence that the SCA autoantibody may at times be pathogenic and cause autoimmune disease.

Anemia, Hemolytic↗
PubMed1990

Flow cytometry: its applications to immunohaematology.

Flow cytometry, using fluorescent probes, has only recently been applied to practical aspects of immunohaematology. It has been used for the detection and quantitation of cell-bound immunoglobulins and complement, minor cell populations, cellular antigens, and platelet and granulocyte antibodies. Practical applications of detecting minor cell populations have been successful in determining the extent of fetal maternal haemorrhage; determining the survival of transfused RBCs (small and large volumes); demonstrating RBC chimaerism (e.g. following bone marrow transplantation) and RBC mosaicism (e.g. demonstration of the McLeod phenotype carrier status). A large variety of cellular antigens have been demonstrated on RBCs, platelets and white cells using flow cytometry. Quantitation of RBC antigens by flow cytometry has been found to be much more objective and accurate than the routinely used serological approaches for establishing zygosity in paternity studies. Flow cytometry has been found to be a sensitive, objective and reproducible method for detecting platelet auto-and alloantibodies, and has also been used to detect granulocyte antibodies. More recently, it has been used to detect antibodies to monocytes and lymphocytes. As flow cytometers become more commonly available, many of these applications may become routine in clinical pathology laboratories.

Antigens, Surface↗
PubMed1990

Correlation between in vivo hemolysis and the amount of red cell-bound IgG measured by flow cytometry.

A flow cytometry method was used to compare the amount of red cell (RBC)-bound IgG in 73 patients with and without immune hemolytic anemia (IHA). The positive results in 10 of the direct antiglobulin tests (DATs) were idiopathic, and those in 25 were due to methyldopa therapy; 38 of the 73 DAT-positive patients were babies born to women with IgG alloantibodies of potential clinical significance. Normal blood donors with (n = 30) and without (n = 121) positive DATs were also tested. RBCs that had been strongly sensitized (4+ indirect antiglobulin test) in vitro with different quantities of IgG anti-D, but that had similar antiglobulin test (AGT) titration scores, could easily be differentiated by flow cytometry. The mean percent fluorescence of RBCs, incubated with fluorescein-labeled anti-IgG, from neonatal patients with IHA was higher than that of RBCs from those without IHA, but there was no statistical difference in the other groups. There was considerable overlap in the respective ranges of percent fluorescence of RBCs from patients with and without IHA in all groups. It was not possible to define a clear quantitative threshold differentiating patients with IHA from those without. Although flow cytometry was more precise and reproducible than standard serology (e.g., AGT titration scores), correlations of the amount of RBC-bound IgG and in vivo hemolysis were similar.

Anemia, Hemolytic, Autoimmune↗
PubMed1989

Isoimmunization to Cromer antigen in pregnancy.

Pregnancy in a woman isoimmunized to Cromer antigen, a high-frequency antigen, is reported. Neither of her two Cromer antigen-positive infants was affected with hemolytic disease of the newborn. Autologous blood or that from a compatible Cromer antigen-negative relative may be frozen and stored for possible transfusion in a pregnant woman with anti-Cromer antigen antibodies.

Adult↗
PubMed1989

Investigations of the potential for five beta-lactam antibiotics to elicit type II hypersensitivity reactions in rats and monkeys.

Immunologic reactions are occasionally elicited in patients by various beta-lactam antibiotics (e.g., penicillins and cephalosporins). A relatively rare reaction (type II hypersensitivity) may involve antibody-mediated destruction of erythrocytes, leukocytes, and/or platelets. During the safety evaluation of several modified beta-lactam compounds (carbapenems), hemolytic anemia and/or neutropenia were observed in rhesus monkeys, and anemia, neutropenia, and thrombocytopenia in rats, after approximately 2 weeks of intravenous administration. Antiglobulin tests and other clinicopathologic findings indicated an immune basis for the cytopenias. A review of summaries of the preclinical data for numerous marketed beta-lactam antibiotics revealed that various cytopenias of unknown etiology were commonly seen in animals given high doses of these compounds. To determine whether these hematologic abnormalities were related to those produced by the above carbapenems, we investigated the potential of five widely used beta-lactam antibiotics (penicillin G, cephalothin, cefazolin, cefoperazone, and cefamandole) to elicit immune-mediated cytopenias in rhesus monkeys and Sprague-Dawley rats when given intravenously. After approximately 1 month of administration of these compounds at a dose level of 500 mg/kg/day, slight anemia occurred in several drug-treated monkeys; however, direct and indirect antiglobulin tests were negative for all animals, indicating that the anemias were not immune-mediated. In rats, no drug-induced hematologic changes were observed after 1 month of intravenous administration of 500 and 1000 mg/kg/day of each of the beta-lactams. In addition, direct antiglobulin tests were negative in rats. Therefore, it appears that the ability of certain carbapenem antibiotics to produce a high incidence of type II hypersensitivity reactions in animals is not typical of beta-lactam compounds in general.

Animals↗
PubMed1989

Quantitation of fetal-maternal hemorrhage by flow cytometry. A simple and accurate method.

A simple and objective assay was developed for the detection and quantitation of fetal-maternal hemorrhage with the use of flow cytometry. In vitro prepared control mixtures of 10%, 2%, 1%, 0.5%, 0.25%, 0.125%, and 0.06% D+ RBCs in D- RBCs were tested (8-11) different times by flow cytometry and gave mean % D+ results of 11.10%, 1.90%, 0.92%, 0.45%, 0.24%, 0.11%, and 0.05%. The coefficient of variation of preparing and testing these mixtures ranged from 11.0 to 15.9% for the 10-0.125% mixtures. Thus, flow cytometry was accurate, reproducible, and sensitive. Flow cytometry was compared with Du tests, rosette tests, and acid elution. The Du test was highly variable because it was not sensitive enough to detect a significant bleed (approximately 0.6%) in some cases and too sensitive (necessitating quantitation of an insignificant bleed) in others. The rosette test was too sensitive. Acid elution and flow cytometry results did not always agree; acid elution results were approximately twice as high as flow cytometry. The authors believe flow cytometric detection of D+ red blood cells to be more accurate than the detection of fetal hemoglobin by acid elution techniques, which is known to have poor reproducibility. Postpartum samples from 56 D- women who delivered D+ babies were tested. Fifty-two had fetal bleeds less than 0.3% by acid elution and flow cytometry; all had negative Du test results, but there were two false positive results with the use of the rosette technique. Four had significant bleeds (greater than or equal to 0.6%); in all four cases the flow cytometry results were lower than the acid elution results. The authors were able to quantitate a bleed of fetal RBCs, which were D+ only by the Du test, in a D- mother with the use of flow cytometry, and D+ RBCs in a mother whose RBCs were of the rare DVI mosaic phenotype. This would not have been possible with the use of the standard Du or rosette techniques.

Erythrocyte Count↗
PubMed1989

Monocyte monolayer assay: an efficient noninvasive technique for predicting the severity of hemolytic disease of the newborn.

The authors performed monocyte monolayer assays (MMAs) with the use of normal donor monocytes, and homologous reagent red blood cells, sensitized in vitro, with antibodies in maternal sera. The sera were from 16 pregnant women with Rh antibodies, drawn at the time of amniotic fluid analysis. They compared the predictive value (PV) of the MMAs and the delta OD 450 of amniotic fluid in forecasting the need for transfusing the infant. The PV of the delta OD 450 result in Liley zone mid II-III was 100%, but in zones 0 to low II it was only 60% (13 samples from ten women were in these zones but four babies required transfusion). In contrast, the PV of a positive (greater than 20% reactivity) MMA was 91% (one false positive result) and the PV of a negative MMA was 100%. Thus, the MMA was more efficient than amniotic fluid analysis at predicting hemolytic disease of the newborn severe enough to require transfusion. The noninvasive MMA could be used as a screening test, reducing the number of amniocenteses or ultrasound evaluations performed on Rh-sensitized women.

Amniotic Fluid↗
PubMed1988

Erythromycin-induced immune hemolytic anemia.

A 3-year-old female receiving Pediazole (erythromycin ethylsuccinate and sulfisoxazole) for tonsillitis and otitis media developed severe hemolytic anemia. No serum drug-dependent antibodies could be demonstrated with an in vitro 'immune-complex' method using Pediazole, pure erythromycin ethylsuccinate or pure sulfisoxazole. However, a method using red cells coated with erythromycin base showed in vitro lysis of the erythromycin-coated red cells. This is only the second case of immune hemolytic anemia associated with erythromycin and the first where in vitro drug-dependent hemolysis was demonstrable.

Anemia, Hemolytic↗