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PubMed1998

[Hemolytic anemia and thrombocytopenia associated with anti-omeprazole antibody].

An 80-year-old woman was admitted with anemia, jaundice and a bleeding tendency about 5 weeks after starting omeprazole. On admission, the hemoglobin was 6.4 g/dl, platelets 0.1 x 10(4)/microliter, leukocyte count 7,500/microliter, and reticulocyte count 325/1000. The total bilirubin was 1.9 mg/dl, indirect bilirubin 0.6 mg/dl, lactate dehydrogenase 572 IU/l, and haptoglobin < 10 mg/dl. Both the direct and the indirect Coombs' tests were positive. The platelet-associated IgG (PAIgG) was 1,100.0 ng/10(7) cells. A decrease in the complement value was observed. There was an increase in the number of megakaryocytes and erythroblasts in the marrow film. After omeprazole administration was halted, her hemoglobin and platelet levels gradually returned to normal. On the 27th hospital day, the direct Coombs' test was positive but the indirect Coombs' test became negative. The PAIgG value also returned to normal, and she was discharged on the 59th hospital day. The acute phase of the drug-induced lymphocyte stimulation test was negative, however, we detected the IgG antibody to omeprazole. In the recovery phase, the IgG value decreased. Forty days after discharge, the direct Coombs' test had become negative. This is apparently the first report of a patient with acute hemolytic anemia and thrombocytopenia due to omeprazole through an immune complex mechanism.

Acute Disease↗
PubMed2001

Maternal anti-D prophylaxis during pregnancy does not cause neonatal haemolysis.

OBJECTIVE: To evaluate signs of haemolysis in babies of Rh-D negative mothers who underwent prophylaxis with anti-D immunoglobulin during pregnancy. DESIGN: The following were evaluated in all babies of Rh-D negative mothers born within a three month period in our department: haemoglobin level, packed cell volume, mean corpuscular volume, reticulocytes, bilirubin level, and direct Coombs' test (direct anti-globulin test). The babies were divided into two groups according to number of doses of anti-D immunoglobulin received by the mother (one or two), and then further divided by their Rh status (negative or positive). Findings were also compared with a control group of babies of O-Rh positive mothers. RESULTS: The study group consisted of 101 babies and the control group of 37 babies. No statistically significant differences were found for any of the haematological variables between the babies of mothers who received one or two doses of anti-D immunoglobulin, or between the Rh negative babies (n = 35), and the controls. Although 20% of the Rh positive babies born to mothers receiving two doses of anti-D immunoglobulin had a positive result in the direct Coombs' test compared with only 2.4% of the babies of mothers treated with only one dose, no signs of haemolysis were documented in the babies with a positive Coombs test. CONCLUSION: The prevention of Rh isoimmunisation with anti-D immunoglobulin (one or two doses) during pregnancy does not jeopardize the newborn. Blood group typing and direct Coombs' test should be performed in every newborn of an Rh negative mother to establish whether there is a necessity to administer anti-D. In the presence of a positive direct Coombs' test, the type of antibodies should be identified.

Analysis of Variance↗
PubMed1983

Experimental erythrocyte autoantibodies. V. Induction and suppression of red blood cell autoantibodies in mice injected with rat bromelain-treated red blood cells.

Mice injected with rat red blood cells (RBC), or rat bromelain-treated (brom) RBC, produce RBC autoantibodies and suppressor cells that specifically inhibit the autoimmune response without inhibiting the net production of antibodies against rat RBC. It has been investigated whether suppressor cells induced by injections of rat RBC are effective in preventing autoantibody production induced by rat brom RBC and vice versa. Autoantibodies were induced in C3H mice by weekly ip injections, each 0.2 ml, of a 6% suspension of rat RBC or rat brom RBC. Autoantibody production was assayed using Coombs' test. Suppressor cells were present in the spleens of mice positive in Coombs' tests and were shown by intravenous injections of 40 X 10(6) viable cells per mouse into untreated syngeneic mice 18 hr before the first injection of rat RBC or rat brom RBC. Autoantibodies eluted from mice positive in Coombs' tests after injections of rat RBC or brom RBC were absorbed by either type of rat RBC but not by RBC from sheep. This suggests that rat RBC and rat brom RBC display antigens that are similar, if not identical, to autoantigens on the mouse RBC. Spleen cells from mice injected with rat RBC suppressed autoantibodies induced by both rat RBC and rat brom RBC. In contrast, spleen cells from mice injected with rat brom RBC suppressed autoantibodies induced by rat brom RBC but not those induced by unmodified rat RBC. This differential suppression may be due to the removal from rat RBC, by bromelain, of a suppressor site and/or autoantigens of some specificities. Thus rat brom RBC may not induce the total range of specificities of autoantibodies, and of suppressor cells, induced by rat RBC.

Animals↗
PubMed1987

Early diagnosis of ABO haemolytic disease of the newborn.

To assess the usefulness of cord blood tests in diagnosing ABO-haemolytic disease of the newborn (ABO-HDN), 132 term, adequate for gestational age (AGA) neonates were evaluated. The tests studied and their significant results were: quantitative elution test (greater than or equal to 1/16), direct Coombs test (positive), bilirubin concentration (greater than or equal to 4 mg/dl). In none of the 56 O+ newborn infants delivered by O+ women were the results of any test positive. Of the 76 A+ and B+ newborn infants delivered by O+ women, 17 (22%) developed ABO-HDN. When the combined result of any two tests was positive, the sensitivity, the specificity and the positive predictive accuracy for the diagnosis of ABO-HDN was higher than for any one of the isolated tests. The probability that ABO-HDN was present when the results of at least two cord blood tests were positive was 70%, and the probability that ABO-HDN was not present when less than two cord blood tests gave positive results was 93%. It is suggested that the combination of quantitative elution test, bilirubin concentration and direct Coombs test in the cord blood is useful for an early diagnosis of ABO-HDN.

ABO Blood-Group System↗
PubMed1986

Hematologic correlates and the role of erythrocyte CR1 (C3b receptor) in the development of AIDS.

Circulating immune complexes (CICs) are common in patients with the acquired immunodeficiency syndrome (AIDS) as in anemia. In our previous reports, we observed that the deposition of CICs on erythrocytes via C3b receptors (CR1) resulted in a defective CIC clearing system of erythrocytes and in high membrane osmotic fragility of such erythrocytes. We investigated the functional activity of erythrocyte CR1 in 89 patients with AIDS, 41 with AIDS related complex (ARC), 102 healthy homosexual volunteers, and 37 heterosexual males, in relation to the presence of CICs, antibody to lymphadenopathy associated virus/human T lymphotropic virus-III (LAV/HTLV-III), anemia, and the direct and indirect Coombs' tests. CICs were frequently found in all groups except heterosexual males. Absence of CR1 activity was observed in 85% of patients with AIDS, and in 59% with ARC. Impaired CR1 activity also occurred in the homosexual volunteer group. Positive direct Coombs' test and the presence of CICs correlated inversely with CR1 activity while a lowered hematocrit and the presence of antibody to LAV/HTLV-III correlated directly. Neither the sera nor the eluates from erythrocytes with a positive IgG Coombs' test contained IgG antibody against erythrocytes. This suggests decremental loss of CR1 activity progressing from asymptomatic LAV/HTLV-III antibody positive homosexual volunteers to the prodromal spectrum of ARC and finally progressing to a total disappearance in overt AIDS. Of 8 homosexuals volunteers demonstrating the composite of impaired CR1 activity, positive antibody to LAV/HTLV-III, and polyvalent positive direct Coombs' test (with gamma, mu, and C3b), all developed ARC or overt AIDS within 2 years of these observations.

AIDS-Related Complex↗
PubMedDate not supplied

[Autoimmune hemolytic anemia induced by alpha methyldopa].

We present in this paper two cases of auto-immune hemolytic anemie caused by ingestion of alpha-metildope Coombs' test positive. We suggest to make Coombs test to every patient in whose treatment has been included the use of alpha-metildope.

Administration, Oral↗
PubMed1994

Ranitidine-associated autoimmune hemolytic anemia in a health maintenance organization population.

Reversible hematologic abnormalities including hemolytic anemia [1] with a positive direct Coombs' test have been associated with ranitidine. In addition to the case report cited above, the U.S. Food and Drug Administration had received five other cases of hemolysis associated with recent intake of ranitidine as of February 1991. To investigate the possible association of ranitidine with autoimmune hemolytic anemia, a study was conducted to determine how often diagnoses of hemolytic anemia or abnormal Coombs' test results followed dispensing of ranitidine using the automated medical and pharmacy records of a large health maintenance organization. No occurrences of hemolytic anemia were identified among 12,054 individuals following 38,686 prescriptions for this medication. The 95% upper confidence bound was 3.1 cases/10,000 exposed persons. One abnormal direct Coombs' test with mild anemia was discovered during routine prenatal testing of an asymptomatic patient who was dispensed ranitidine two and a half months previously. Hemolysis, however, was not demonstrated and an association with prior ranitidine use could not be confirmed. Additional analyses indicate that in only 30% of ranitidine courses was a blood count obtained. In those courses with hematocrits below 40%, less than 1% had a Coombs' test performed. Chart review suggests that the majority of individuals with severe anemia have alternative explanations other than autoimmune hemolysis for their anemia. This analysis indicates that ranitidine is unlikely to be a common cause of clinically recognized autoimmune hemolytic anemia and demonstrates the utility of large automated medical and pharmacy data bases to conduct post-marketing studies of spontaneously reported drug effects.

Ambulatory Care↗
PubMed2003

Investigation of the mechanism of drug-induced autoimmune hemolytic anemia in cynomolgus monkeys elicited by a repeated-dose of a humanized monoclonal antibody drug.

We investigated the mechanism of hemolytic anemia detected in a repeated-dose toxicity study using cynomolgus monkeys that were treated with a humanized antibody drug. This drug was an IgG1 monoclonal antibody (MoAb) that binds to the human HM1.24 antigen named anti-HM1.24 MoAb. The presence of the HM1.24 antigen on the erythrocyte membranes and the erythrocyte agglutination following the addition of anti-HM1.24 MoAb was examined. In addition, an indirect Coombs' test, a hemolysis assay and the measurement of anti-single stranded-DNA antibodies were performed using test animal serum or plasma. The specific binding of FITC- and 125I-labeled anti-HM1.24 MoAb to the erythrocyte membrane was not observed. HM1.24 antigen was not identified on the erythrocyte membranes. However, a high concentration (more than 713 microg/mL) of anti-HM1.24 MoAb hemagglutinated the erythrocyte suspensions. The cause of this agglutination was unclear, but it is assumed that the non-specific binding and/or adhesion caused the direct agglutination. In the examination using test serum from the anemic monkeys, a positive reaction in the indirect Coombs' test was noted. Moreover, in these Coombs' test-positive animals, the production of anti-single stranded-DNA antibodies was sequentially increased. In the female monkey sacrificed in extremis due to severe anemia, an in vitro hemolytic reaction was detected attributable to complement activation. From these results, the hemolytic anemia detected in the repeated-dose toxicity study was diagnosed as a drug-induced autoimmune hemolytic anemia (AIHA) and the primary cause was assumed to be production of IgG class anti-erythrocyte autoantibodies.

Anemia, Hemolytic, Autoimmune↗
PubMed1994

Prediction of the development of neonatal hyperbilirubinemia in ABO incompatibility.

BACKGROUND: ABO incompatibility is now the most common cause of isoimmune hemolytic disease of the newborn here. Although hemolytic disease because of ABO incompatibility is clinically milder than that from Rh incompatibility, severe hemolysis occasionally occurs, and some cases require exchange transfusion. It is desirable to assess the accuracy of a group of tests to predict the development of neonatal hyperbilirubinemia in ABO incompatibility. Then, early treatment is available for minimizing the frequency of exchange transfusion. METHODS: Eighty-eight healthy full-term newborn infants born to blood group 0 mothers were studied and divided into four groups. Each baby weighed 2.5 Kg or more, had no evidence of G-6-PD deficiency. Group 1 consisted of 29 blood group A or B infants with hyperbilirubinemia (serum bilirubin levels > or = 15 mg/dl) and/or icterus praecox. Group 2 consisted of 24 blood group A or B infants without hyperbilirubinemia (serum bilirubin levels < 15 mg/dl). Group 3 consisted of 7 blood group 0 neonates with hyperbilirubinemia. Group 4 consisted of 28 blood group 0 neonates without hyperbilirubinemia. Titers of maternal IgG anti-A and anti-B antibodies were measured. Cord blood was used to performed direct Coombs' test and for bilirubin level determinations. RESULTS: A total of 18 (62.1%) mothers had IgG anti-A or anti-B titers > or = 512X in Group 1. The majority of mothers (91.5%) in Group 2, 3 and 4 had anti-A or anti-B titers < or = 128X. Thirteen (44.8%) neonates in Group 1 had positive direct Coombs' test of the cord blood. Only one neonate (4.2%) in Group 2 and one neonate (3.6%) in Group 4 had positive direct Coombs' test. A total of 12 neonates (41.4%) in Group 1 had cord bilirubin levels > or = 4 mg/dl, whereas none in the other groups had cord bilirubin levels > or = 4 mg/dl. CONCLUSIONS: ABO incompatible newborn infants with maternal IgG anti-A or anti-B titers > or = 512X, cord bilirubin levels > or = 4 mg/dl or positive direct Coombs' test of the cord blood represent a "high risk" category, and should be placed in hospital where frequent re-evaluation and appropriate therapy are available.

ABO Blood-Group System↗
PubMed2003

[Autoimmune hemolytic anemia with complement-positive direct antiglobulin test].

Autoimmune hemolytic anemia (AIHI) is an infrequent disease in the pediatric age group. Its diagnosis is given by the direct antiglobulin test (DAT) or Coombs' test, which determines which type of globulin (IgG or complement) is the cause of the hemolysis. The type of globulin involved determines the etiology of AIHI, which is usually confirmed by positive results of other laboratory investigations such as cold agglutinin determination or the Donath-Landsteiner test. We present three cases of AIHI. DAT was positive to complement with diverse etiology: warm antibody with IgG-negative DAT, cold agglutinins associated with infectious mononucleosis, and Doth-Landsteiner antibodies. In all patients, empirical treatment with corticosteroids was initiated. The treatment was withdrawn or continued, depending on the final etiology of AIHI.

Adolescent↗
PubMed1982

[Antiprothrombinase type of circulating anticoagulants during acute disseminated lupus erythematosus].

We report the observations of 4 young women suffering from SLE witha circulatig antiprothrombinase anticoagulant. Antiprothrombinase is the most frequent circulating anticoagulant found in SLE (5 to 10 p. 100). SLE is the main aetiology for antiprothrombinase (over 50 p. 100). It is called 'lupus anticoagulant'. Some symptoms seem to be more frequent in SLE with antiprothrombinase. Such are biological signs (false positive tests for syphilis. Coombs test, thrombopenia, prothrombin deficiency) and clinical signs (venous or arterial thrombosis particularly if oestroprogestative treatment is taken, bleeding if thrombocytopenia or deficiency of prothrombin; repetitive abortion and may be neuropsychiatric signs). Antiprothrombinase is an autoantibody (IgG or IgG + M) polyclonal in SLE, with antiphospholipid activity. It could decrease the production of prostacyclin (PGI2) from free arachidonic acid derived from membrane bound phospholipids. Immunological properties of antiprothrombinase could account for clinical and biological associated signs.

Acute Disease↗
PubMed1982

[Haptoglobins, streptococcus agglutination and streptococcal infections].

The haptoglobins in man and in mammals react with streptococci bearing the T4-antigen. Hp 2-2 and Hp 2-1 react with high titres like complete agglutinins while Hp 1-1 acts like a blocking antibody. It is surprising to observe the similarity of the behaviour of the haptoglobins and of IgG and IgM. Streptococci carrying Hp 1-1 yield a positive Coombs-test. The Coombs-serum however, is an anti-human-haptoglobin-body from sheep. By means of supplements it has been possible to increase partly considerably the titres of Hp 2-1 and Hp 2-2 against the streptococci.

Agglutination↗