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PubMed2002

Rituximab-based chemotherapy for steroid-refractory autoimmune hemolytic anemia of chronic lymphocytic leukemia.

Autoimmune hemolytic anemia (AIHA) is a well known complication of chronic lymphocytic leukemia (CLL). Steroids are the first line of treatment and there are limited effective treatment options for steroid refractory AIHA of CLL. Rituximab, an active agent against B cell malignancies, has also been noted to be active in certain autoimmune hematologic disorders. We used a combination of rituximab, cyclophosphamide and dexamethasone (RCD) in eight CLL patients with steroid refractory AIHA. Rituximab was given at a dose of 375 mg/m(2) i.v. on day 1 (D-1). Cyclophosphamide was given at a dose of 750 mg/m(2) on D-2. Twelve mg of dexamethasone was given i.v. on D-1, D-2 and orally from D-3 to D-7. Cycles were repeated every 4 weeks till the best response. Response in AIHA was evaluated by frequent blood counts and Coombs test. All eight patients achieved a remission of their AIHA. Median pretreatment hemoglobin was 8.3 g/dl and post-treatment hemoglobin was 14.3 g/dl. Five patients converted to Coombs negative after RCD. Median duration of response was 13 months (7-23+). Retreatment with RCD was also effective in achieving a response on relapse of AIHA. Our results indicate that a rituximab-based combination regimen (RCD) is highly effective in treating steroid refractory AIHA of CLL.

Aged↗
PubMed1983

Antinucleolar antibody associated with lupus erythematosus in a dog.

A nucleolar pattern of fluorescence was detected in an Antinuclear Antibody (ANA) test on serum of an 8-year-old Collie with Systemic Lupus Erythematosus (SLE). Skin disease characterized by a lymphoplasmacytic infiltrate and epidermal necrosis and a positive Coombs' test supported the diagnosis. The dog responded to immunosuppressive drugs and continues to do well on maintenance therapy.

Journal Article↗
PubMed1991

[An elderly case of systemic lupus erythematosus associated with herpes zoster, anemia, and hemiparesis].

An elderly case of systemic lupus erythematosus (SLE) with suspected hemolytic anemia was experienced. A 70 year-old female was admitted to our hospital on December 31 with complaints of herpetic eruption. She complained of arthralgia since 3 month prior to her admission. The positive findings on examination were skin eruption in the left chest, a systolic heart murmur and a palpable elastic hard liver. Laboratory data showed raised erythrocyte sedimentation rate of 149 mm per hour, decreased Hb (10.1 g/dl), decreased hematocrit (30.0%), increased reticulocytes (33%1000), decreased thrombocytes (73,000/mm3), increased gamma-globulin (33%) and positive rheumatoid factor. During admission, she developed anemia. A stool test for occult blood was negative. The haptoglobin was 38.8 mg/dl and bone marrow aspiration showed increased erythropoiesis, suggesting features of immune hemolytic anemia, except she was negative on Coomb'test. Eye fundi were similar to case of typical bleeding observed in SLE. Concerning immunological findings, the antinuclear factor was x 1280 and the anti-dsDNA antibody was x 80, on which a diagnosis of SLE was based. She experienced numbness of the left arm and developed left hemiparesis 2 days later. Therapy with 15 mg/day prednisone obtained a good response and anemia, abnormal immunological findings and hemiparesis disappeared.

Aged↗
PubMed1984

Males with neonatal hyperbilirubinemia examined at 18 years of age.

An 18 years follow-up study of 55 males with neonatal hyperbilirubinemia born in 1962/63 was done at the military draft board examinations in 1981. The medical and psychological tests were compared to the tests of the total cohort of Norwegian conscripts. Of those examined at 18 years of age 7.3% was unfit for military service, compared to 6.2% in the total cohort. Ten organ systems were clinically examined with no significantly increased frequency of unfitness among the index cases. Intelligence testing was done on 39 of the studied subjects, the mean score being the same as in the total cohort of Norwegian conscripts. However, the seven infants with a positive Coombs' test and hyperbilirubinemia for 5 days or more had a significantly lower mean intelligence score than the national average.

Adolescent↗
PubMed1996

Decreased fetal erythropoiesis and hemolysis in Kell hemolytic anemia.

OBJECTIVE: Lower changes in optical density (450 nm) measurements have been reported in fetuses with anti-Kell anemia compared with those anti-D anemia. The purpose of this investigation was to determine if hemolysis and erythropoiesis differ between anti-Kell and anti-D hemolytic disease. STUDY DESIGN: Ninety-three pregnancies complicated by either anti-D or anti-Kell alloimmunization were evaluated. Fetal blood samples obtained at the first cordocentesis were tested for the red blood cell antigen type, hemoglobin, hematocrit, reticulocyte count, nucleated red blood cells, total serum bilirubin concentration, umbilical venous respiratory blood gases, serum erythropoietin level, and strength of the direct Coombs test. To determine the evolution of hemolytic anemia in the two antigen groups, these laboratory parameters were repeated on the fetal blood samples triggering the decision to perform a fetal intravascular transfusion (hematocrit <30%). RESULTS: A total of 65 of 93 fetuses were antigen positive (11 for Kell and 54 for RhD). The mean gestational age and laboratory measurements of antigen- positive, nonanemic fetuses at first blood sampling did not differ significantly between groups. There was a strong inverse relationship observed between the hemoglobin concentration and reticulocyte count independent of gestational age in the anti-D group but not in the anti-Kell group. Eight (73%) fetuses with anti-Kell antibodies and 37 (69%) with anti-D antibodies underwent intravascular transfusion. At the cordocentesis when the decision for transfusion was made, anti-Kell anemic fetuses had lower reticulocyte counts and total bilirubin concentrations. The strong inverse relationship between the hemoglobin and reticulocyte count was again seen only in the anti-D group. In both groups, fetal erythropoietin increased significantly between the first and last blood samplings and in each group were negatively correlated with hemoglobin independent of gestational age. CONCLUSION: Anti-Kell anemic fetuses have lower reticulocyte counts and total serum bilirubin levels than do comparable anti-D anemic fetuses. This finding argues in favor of fetal blood sampling rather than amniotic fluid analyses for the management of fetal hemolytic disease resulting from Kell antibodies. Unlike RhD alloimmunized fetuses, these fetuses do not manifest an inverse relationship between hemoglobin concentration and reticulocyte count. We speculate that compared to anti-D fetal anemia, anti-Kell anemia is associated with increased hemolysis of nonhemoglobinized or incompletely hemoglobinized erythroid precursors.

Anemia, Hemolytic↗
PubMed1985

Enzyme linked direct antiglobulin tests in patients with autoimmune haemolysis.

Enzyme linked and agglutination direct antiglobulin tests were carried out on blood samples from 219 patients suspected of having autoimmune haemolysis. The enzyme linked tests were more sensitive: they could detect the small amounts of IgG, IgA, and IgM which are normally present on red cells and showed increased amounts of cell bound immunoglobulins in patients with Coombs test negative autoimmune haemolysis. Many patients had immunoglobulins of more than one class bound to their red cells; considering the degree of haemolysis in individual patients, it appeared that the different immunoglobulin classes acted synergistically in effecting red cell destruction, even in amounts too small to be detected by the agglutination tests. In patients with cold reacting autoantibodies and complement coating of the red cells active haemolysis was found (with one exception) where IgM was detected on the cells by the enzyme linked method. Elution studies indicated that immunoglobulins detected just by the enzyme linked techniques were red cell antibodies. Both enzyme linked and agglutination tests were negative in 66 patients: 61 of these had no evidence of haemolysis, and in the other five the haemolysis was not autoimmune in origin.

Alkaline Phosphatase↗
PubMed1994

Autoimmune haemolytic anaemia in a child with MHC class II deficiency.

A 3 year old Turkish girl is described who was suffering from major histocompatibility complex (MHC) class II deficiency syndrome, which is characterised by the lack of expression of HLA class II antigens on mononuclear cells. The presence of HLA class II genes was demonstrable at the DNA level. Combined immunodeficiency was indicated by hypogammaglobulinaemia and the absence of delayed type hypersensitivity on skin testing. Further, she was unable to produce specific antibodies towards foreign antigens and suffered from recurrent pulmonary, gastrointestinal, and septic infections from the third month of life. The clinical course was complicated by a Coombs test positive haemolytic anaemia due to the production of autoantibodies against the rhesus "e' antigen, a non-glycosylated protein antigen. Haemolysis could be controlled by oral steroid treatment. This case is of interest as it shows that despite the absence of HLA class II antigens and combined immunodeficiency autoimmune reactions with production of specific autoantibodies directed to protein antigens are possible.

Anemia, Hemolytic, Autoimmune↗
PubMed1978

Double-blind comparison of cefamandole and penicillin in pneumococcal pneumonia.

We conducted a prospective, randomized, double-blind comparison of intravenous penicillin and cefamandole in the therapy of pneumococcal pneumonia. Patients received either 1 g of cefamandole or 600,000 U of aqueous penicillin G every 6 h. Of the 100 patients entered into the study, 96 had clinical and radiographic evidence of pneumonia. Microbial etiology was determined from the results of sputum and blood cultures and/or sputum Gram stains. Streptococcus pneumoniae was pathogenic in 49 patients, of whom 24 received cefamandole and 25 received penicillin. There was no statistically significant difference in the response or cure rate. Of the 100 patients, 93 were treated for 3 days or more and were evaluated for adverse effects and toxicity. There was no significant difference between cefamandole-treated and pencillin-treated patients in the incidence of colonization, superinfection, phlebitis, thrombocytosis, decrease in hematocrit, or elevated liver function tests. Eosinophilia occurred more frequently in patients treated with penicillin (20 of 42) than in those treated with cefamandole (11 of 42 (chi square, P < 0.05). Only one patient receiving cefamandole developed a positive direct Coombs test. No patient in either group developed meningitis. We conclude that, with the doses and route of administration employed in this study, cefamandole is as effective as penicillin in the therapy of pneumococcal pneumonia without an increased incidence of colonization, superinfection, or adverse effects.

Adult↗
PubMed1980

[Neuraminidase-producing pneumococci in the pathogenesis of hemolytic-uremic syndrome].

Hemolytic-uremic syndrome (HUS) accompanied by pneumococcal infections forms a characteristic subgroup of HUS. Pneumococcal neuraminidase splits off neuraminic acid from the glycoproteins present on the surface of red cells, thrombocytes and endothelial cells, and thus exposes the hidden Thomsen cryptantigen (T-Ag). The T-Ag can then react with a complement-fixing antibody of the IgM class which is present in all human plasmas after the age of 6 months. Early diagnosis of T-transformation should be attempted. Highly suggestive hints are: pneumonia, hemolytic anemia, reticulocytopenia, difficulties in ABO typing, a positive direct Coombs test and a positive minor cross-match. The definite diagnosis of T-transformation is established with the aid of anti-T agglutinins from Arachis hypogaea, the common peanut. Two children aged 19 and 22 months with pneumonia, Coombs-positive hemolytic anemia, HUS and exposure of the T-Ag on the red cell membrane are described. In one of them, circulating neuraminidase and circulating pneumococcal antigen of serotype 3 were found. In both children exchange transfusions resulted in elimination of circulating neuraminidase and of T-transformed red cells prone to hemolysis.

Female↗
PubMed2002

[Characteristics of autoimmune hemolytic anemia in adults: retrospective analysis of 83 cases].

PURPOSE: To describe the main characteristics and outcome of adult's acquired immune hemolytic anemias (AIHA). To analyse the relevance of the complementary tests performed for the search of an underlying disease. METHODS: Retrospective (1980-2000) monocentric study. INCLUSION CRITERIA: age above 16, AIHA defined by an hemoglobin level below 12 g/dl in men and 11 g/dl in women, with hemolysis and/or a positive direct Coombs test and/or the presence of cold agglutinins (threshold 1/500) and/or in the absence of any other cause. RESULTS: Eighty three patients included (56 women and 27 men), with a mean age of 56 years (+/- 22) at AIHA onset including: 72 patients (87%) with warm antibody AIHA and 11 (13%) with cold agglutinin disease. The mean follow-up was 48 months (median 22 months). Among the 72 patients with warm antibody AIHA, the specificity of autoantibodies was: IgG + complement (43%), IgG (32%) or complement alone (25%); cold agglutinins (titre from 1/60 to 1/512) were detected in 15 (20%) of the patients. Antinuclear antibodies were detected (threshold: 1/80) in 33% of the cases. Hypogammaglobulinemia on serum protein electrophoresis (SPE) was significantively associated with the presence of an underlying non-Hogkin lymphoma (NHL). The CT-scan of the the chest and abdomen which was performed in 50% of the patients, showed abnormalities other than a spleen enlargement in 25% of the cases. The medullar biopsy (MB) was abnormal in 7 of 26 cases (27%) but lead by itself to the diagnosis of NHL in a single case. Thrirty seven (51%) of warm antibody AIHA cases were finally considered to be "secondary" to an underlying disease namely: NHLs (n = 14), Hogkin's disease (n = 1) connective tissue disease (CTD) (n = 14), drug-induced AIHA (n = 3), miscellaneous (n = 5). In 6 out of 14 cases (43%) of NHL's associated AIHA, the onset of AIHA precedes the NHL from 22 to 66 months. The response rates to different therapeutic regimens did not significatively differ when "secondary" and "idiopathic" AIHA were compared. Overall, 13 patients (15.6%) died mainly from infectious complications (n = 5) or an underlying NHL (n = 5). CONCLUSIONS: In more than half of the cases AIHA are associated with an underlying disease and AIHA may precede the onset of a NHL for a long period. In the absence of a clinically apparent underlying disorder, testing for the presence of antinuclear antibodies, a SPE and a CT-scan must be systematic. Conversely, if no abnormalities are found, the relevance of a systematic MB at AIHA onset seems very low.

Adult↗
PubMed2003

[A cold agglutinin disease, difficult to distinguish from paroxysmal cold hemoglobinuria].

A 58-year-old male started passing dark brown colored urine in January 2002. An annual medical examination in the same month revealed a mild anemia and an increased serum LDH level. Because of the instability of the data of his peripheral red cell count and hemoglobin concentration as measuring with a blood cell auto-analyzer, and also the hemolytic findings in a test tube at room temperature (25 degrees C), he was referred to our hospital. Laboratory data revealed Hb 11.2 g/dl, reticulocytes 73.1% (233,000/microliter), indirect-bilirubin 2.8 mg/dl, LDH 757 U/l, and hemosiderinuria, suggesting some intravascular hemolysis. The cold agglutinin titer was > 1,024, direct and indirect Coombs tests were both positive, and the Donath-Landsteiner antibody (D-L antibody) was initially assessed as false positive because of a high titer of cold agglutinin. He was finally diagnosed as having a cold agglutinin disease (CAD) with anti-I autoantibody. Serologic tests for syphilis and mycoplasma, and various virus tests were all negatives. After avoiding cold exposure, his symptoms, including hemoglobinuria, disappeared. However, during 9 months follow-up, he still showed a high titer of cold agglutinin. This case suggests that CAD should be considered when peripheral blood cell count data are unstable as assessed by a blood cell auto-analyzer.

Agglutinins↗
PubMed1978

[Immunoglobulin and antibody content in the blood serum, coprofiltrate and saliva of patients with Sonne dysentery].

The authors studied the immunoglobulin and specific antibodies content of various classes in the serum, coprofiltrates and the saliva of 68 patients suffering from Sonne dysentery and in 48 healthy adult persons. Mancini's test demonstrated a significant elevation of IgG and IgM content in the blood of dysentery patients in comparison with that in healthy persons, and the absence of any changes in the IgA content. The titres of specific IgG-, IgA- and IgM-antibodies in determination in the modified Coombs' test increased consideerably during dysentery infection and were found in high titres during the first week of the disease; they reached the maximum during the second week and persisted at this level for 3 weeks. The greatest antibody elevation was in the IgA-class. Antibodies revealed in the coprofiltrates and the saliva of dysentery patients belonged to IgA- and IgG-class. There proved to be a correlation of the antibody changes in these two secretions.

Adult↗
PubMed1978

Sequestration of neuraminidase-treated erythrocytes. Studies on its topographic, morphologic and immunologic aspects.

Scintigraphic experiments and radioactivity measurements of tissues have shown that the radioactivity of 51Cr-labelled and neuraminidase-treated rabbit erythrocytes is rapidly accumulated in liver and spleen. Sequestration of these erythrocytes by liver and spleen was demonstrated by light and electron microscopy of theses tissues after perfusion of the rabbits with solutions for tissue fixation. In liver the phagocytic activity of Kupffer cells was increased after injection of desialylated erythrocytes, while in spleen a significantly enhanced number of erythrocytes was found attached to the sinusoidal walls and in the reticulum of the red pulp. It was shown by scanning electron microscopy that neuraminidase-treatment did not influence the shape of erythrocytes. Desialylated and 51Cr-labelled erythrocytes from the cow are rapidly cleared from the blood-stream with a half-life time of about 3 h. It was shown in an in-vitro test that they adsorb to surviving slices from liver and spleen derived from the same animal. The amount of radioactivity adsorbed is appreciably enhanced in the presence of homologous serum when compared with buffer only. Human neuraminidase-treated erythrocytes are agglutinated in the direct and especially in the indirect Coombs-tests. The involvement of T-antigen in this phenomenon was largely excluded. The in vitro experiments and antibody consumption tests suggest that immunoglobulins (IgG) and complement from serum may be involved in recognition and sequestration of desialylated erythrocytes by macrophages in vivo.

Animals↗
PubMed2006

Erosive polyarthritis associated with Mycoplasma gateae in a cat.

Erosive polyarthritis was diagnosed in an 11-month-old neutered male Egyptian Mau-cross cat with concurrent glucocorticoid-responsive dermatitis. Clinical signs, synovial fluid analysis, serological tests and radiographic appearance could not differentiate between immune-mediated and infective arthritis. Mycoplasma gateae was isolated by strictly anaerobic culture of the synovial fluid. Treatment with Enrofloxacin led to a rapid improvement of the cat's condition. Two months later the cat was euthanased because of severe glomerulonephritis and direct Coombs' test positive anaemia, possibly caused by mycoplasma infection. M gateae could not be isolated at post-mortem examination.

Animals↗
PubMed1984

In vitro immunoreactivity to propylthiouracil, methimazole, and carbimazole in patients with Graves' disease: a possible cause of antithyroid drug-induced agranulocytosis.

Studies of in vitro immunoreactivity to propylthiouracil (PTU), methimazole (MMI), and carbimazole (CARB), as assessed by peripheral blood lymphocyte transformation and 2 antibody tests, were carried out in 12 patients with Graves' hyperthyroidism who had developed agranulocytosis during treatment with PTU (11 patients) or CARB (1 patient) from 1 week to 10 yr earlier. Significant lymphocyte transformation responses to antithyroid drugs (stimulation indices greater than mean +/- 2 SD for normal subjects) were found in 5 of 6 patients tested, in 1 patient to PTU only, in 3 patients to MMI only, and in 1 patient to both PTU and MMI, but in none of 10 patients currently being treated with PTU who did not develop agranulocytosis. Circulating antibodies causing neutrophil agglutination in the presence of antithyroid drugs were demonstrated, using the indirect Coombs test, in 5 of 7 patients tested, in 2 patients to PTU only, in 3 patients to CARB only and in 1 patient (the only one tested with MMI) to PTU and MMI. Lymphocyte transformation and antibody tests to PTU were both carried out in 6 patients. Of these, both tests were positive in one patient, both negative in 3 patients, and 1 negative and 1 positive in 2 patients. In the 1 patient in whom both tests were carried out with CARB (patient 3), tests were negative, whereas in the 1 patient in whom both tests were carried out with MMI (patient 3), 1 test was positive, whereas the other was negative. Thus, in patients in whom both tests were carried out using the same drug, correlation between lymphocyte transformation responses and the detection of neutrophil antibodies was found in 5 of 6 cases. Antibodies reactive with neutrophils were also detected in 2 of the 5 patients tested using an enzyme-linked immunosorbent assay. In this test antibodies to PTU or MMI were not demonstrated. Possible mechanisms for the neutrophil depression in relation to these findings are discussed. It is concluded that patients with Graves' disease may be prone to develop this complication of antithyroid drug therapy because of underlying immunological abnormalities.

Adolescent↗
PubMed1986

Thrombosis, recurrent fetal loss, and thrombocytopenia. Predictive value of the anticardiolipin antibody test.

To determine the predictive value of the IgG anticardiolipin antibody (ACA) test for thrombosis, recurrent fetal loss, and thrombocytopenia, the clinical features of 121 patients with varying antibody levels were studied. When patients were grouped into high-positive, low-positive, and normal groups according to their ACA levels, there were strong statistical correlations with arterial thrombosis, venous thrombosis, fetal loss, thrombocytopenia, and a positive Coombs' test. At levels of 7 SD and above, the test was highly specific (greater than 80%) and predictive (greater than 70%) for thrombosis, thrombocytopenia, and recurrent fetal loss. This study suggests that the IgG ACA test may be a useful predictor for thrombosis, recurrent fetal loss, and thrombocytopenia in patients with autoimmune disorders.

Abortion, Habitual↗
PubMed1990

[Antigenicity study of cefpirome sulfate].

Immunological properties of cefpirome sulfate (CPR) were examined. The immunogenicity and challenging ability of CPR were examined in guinea pigs by active systemic anaphylaxis (ASA) and homologous 4-hr passive cutaneous anaphylaxis (PCA) tests. The animals given CPR alone intraperitoneally for sensitization and their sera were negative for ASA or PCA reactions, like the results with reference substances, ceftazidime (CAZ) and cephalothin sodium (CET). When each antibiotic plus Freund's complete adjuvant (FCA) was used for sensitization, ASA reactions were observed with CPR, cephaloridine (CER), CET, and cefazolin sodium (CEZ), and PCA reactions, with CPR and CET. CPR had the ability to challenge the ASA and PCA reactions. CER and CET also showed the ability to challenge ASA or PCA reactions, though at low incidences. The cross-reactivity of CPR with commercially available antibiotics was examined by heterologous PCA test and by passive hemagglutination test and its inhibition test. The antiserum used was from rabbits immunized with each antibiotic-ovalbumin conjugate plus FCA, and the antigen was each antibiotic-bovine serum albumin conjugate. CPR cross-reacted markedly with cefotaxime sodium (CTX) having the same side chain at position 7 and showed weak, unidirectional reactions with CAZ and CET. In the in vitro direct Coombs test, the positive reactions noted with CPR were stronger than those with latamoxef sodium, equal to those with CEZ and slighter than those with CTX, CET and benzylpenicillin potassium. In conclusion, in the safety evaluation of CPR, its antigenic potential may not be a problem, like the cases of other antibiotics.

Anaphylaxis↗