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PubMed2002

Autoimmune haemolytic anaemia: pattern of presentation and management outcome in a Nigerian population: a ten-year experience.

Autoimmune haemolytic anaemia (AHA) is one of the commonest autoimmune disorders of man. It is characterised by the binding of anti-erythrocyte autoantibodies to red blood cells and destruction of the coated cells in the reticulo-endothelial system. Autoimnmune disorders are said to be rare in indigenous African population, probably due to the widespread infectious diseases, which impair host's T-cell immunity. This study is therefore aimed at investigating the pattern of presentation and management outcome of patients with AHA seen over a period of 10 years (June 1988 to May 1998) at the Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife. We retrospectively analysed the records of patients with respect to the clinical, haematological, biochemical and serological features of AHA seen within the study period. Diagnosis was based on laboratory features of haemolytic anaemia and/or a positive direct anti-human globulin (Coombs') test after excluding other causes of haemolytic anaemia. Treatment protocol and outcome were noted in all cases. We identified 13 patients with AHA (7 females, 6 males) aged 6-70 (median, 42) years. Six (42%) had secondary AHA and the remaining 8 presented with primary (idiopathic) AHA. Laboratory evidence of haemolysis (bone marrow erythroid hyperplasia and hyperbilirubinaemia) was found in all cases, while the direct Coomb's test was positive in 10 (76.9%) cases. All the patients had moderate-severe anaemia within the course of the disease, requiring blood transfusion. Remission was induced with prednisolone in all except three cases with secondary AHA who died of the primary disease before AHA could be controlled. Follow-up period post-remission ranged between 1 and 78 months. However, 2 (20%) are still being followed-up till the time of this report. This study agrees with the view that autoimmune disorders are not common in Nigerians, as documented for other Africans. It also shows that steroid therapy (prednisolone) is quite effective, especially, in idiopathic AHA, and that red cell transfusion could be useful in life-threatening anaemia.

Adolescent↗
PubMed1981

Interleukin-2 allows in vivo induction of anti-erythrocyte autoantibody production in nude mice associated with the injection of rat erythrocytes.

Mice injected with rat red blood cells developed anti-erythrocyte autoantibodies detectable by a direct Coombs' test. Nude mice injected with rat red blood cells did not develop a Coombs-positive state, but nude mice injected with rat red blood cells plus the T cell helper factor, interleukin-2, produced autoantibodies to autologous mouse erythrocytes. The simultaneous injection of rat red blood cells and allogeneic spleen cells induced an early and vigorous autoantibody response in athymic nude mice as well as in euthymic control mice. These results are interpreted as indicating the possibility of an interleukin-2-stimulated in vivo differentiation (or clonal expansion) of helper T cells in nude mice in response to heterologous erythrocytes which could mediate an autoimmune B cell response.

Animals↗
PubMed1994

[Evaluation of the Chromotitre EIA test in the diagnosis of human brucellosis].

BACKGROUND: The aim of the study was to evaluate the diagnostic efficacy of Chromotitre EIA test for the diagnosis of human brucellosis and compare the same with other classical serologic test. METHODS: A prospective study was performed in 50 patients with active brucellosis. Thirty blood donors, 64 patients with different neoplastic and autoimmune infectious processes, 20 patients with history of brucellosis and 8 subjects with continuous exposure to Brucella at work were analyzed as the control group. RESULTS: Forty-five patients with brucellosis (90%) presented a positive IgM or IgG ELISA, 32 (62%) only IgM, 34 (68%) only IgG and 22 (44%) both immunoglobulins were positive. The sensitivity and specificity of ELISA test jointly evaluating IgM and IgG was 90 and 68%, respectively with these numbers being 62 and 98% and 68% and 38% for ELISA IgM and ELISA IgG. A moderate correlation was found between ELISA IgM with Bengal's Rose test (r = 0.53, p = 0.003) and sero-agglutination (r = 0.63, p = 0.0001) and ELISA IgG with the Coombs test (r = 0.55, p = 0.003). Only acceptable concordance was observed between ELISA IgM and sero-agglutination (kappa = 0.55, p = 0.0001). CONCLUSIONS: The ELISA test evaluated was very useful for the detection of IgM antibodies but was found to be insufficient with respect to IgG antibodies. Despite the slight diagnostic efficacy of the ELISA IgG the combined parallel use of both immunoglobulins achieved a performance similar to that achieved with the classical tests.

Adolescent↗
PubMed2001

False-positive serological tests in acute malaria.

A range of serological tests, including rapid plasma reagin (RPR), Widal test, enzyme-linked immunosorbent assay (ELISA) for human immunodeficiency virus (HIV)-1 and -2, direct Coombs' test (DCT), and rheumatoid factor (RF) were performed in a well-characterised cohort of 100 patients with acute malaria (Plasmodium vivax infection: 31 patients; P. falciparum infection: 69 patients). Twenty-five healthy volunteers from a similar area were used as controls. Three patients from the severe P. falciparum group died, the remainder of the patients recovered completely. A large proportion of these patients showed false-positive serological reactions during the acute stage of infection, which became negative on re-testing, four weeks after recovery. In tropical countries such as India, where malaria is endemic, results of serological tests should be interpreted with caution in a patient with pyrexia of unknown origin (PUO).

AIDS Serodiagnosis↗
PubMed2000

Pemphigus foliaceus in association with systemic lupus erythematosus, and subsequent lymphoma in a cocker spaniel.

A seven-year-old neutered male cocker spaniel was presented with an 11-month history of generalised bacterial dermatitis. There were skin lesions over the entire body, which were round, slightly raised and encrusted. Skin biopsies were collected and the histological findings were consistent with pemphigus foliaceus. Immunohistochemical staining by the indirect immunoperoxidase method was positive, with desmosomal deposition of immunoglobulin (Ig) G. Haematological analysis revealed a regenerative anaemia and profound thrombocytopenia, while a Coombs' test was positive for polyvalent canine Coombs' reagent and anti-dog IgG. An antinuclear antibody test was positive, with a titre of 10,240. An ophthalmic examination demonstrated low tear production (keratoconjunctivitis sicca). Seven months after initial referral, the dog was re-presented with severe generalised peripheral lymphadenopathy. Radiographic evaluation of the thorax and abdomen revealed enlarged cranial mediastinal and sublumbar lymph nodes. Tru-Cut biopsy from an enlarged lymph node confirmed the diagnosis of lymphoma, which was phenotyped as a B-cell tumour. The diagnosis in this case was systemic lupus erythematosus, with the unusual feature of pemphigus foliaceus, and subsequent development of B-cell lymphoma. The case adds further to knowledge of the protean clinical presentations of canine autoimmune diseases and provides additional evidence for the potential association between autoimmunity and immune-system neoplasia in this species.

Animals↗
PubMed2004

Intravenous immunoglobulin G (IVIG) therapy for significant hyperbilirubinemia in ABO hemolytic disease of the newborn.

BACKGROUND: Although intravenous immunoglobulin G (IVIG) therapy has been reported in hyperbilirubinemia of Rh hemolytic disease, its use in ABO hemolytic disease has been reported in only a few studies. In our institute we have observed that almost 30% of babies with hyperbilirubinemia due to ABO hemolytic disease required exchange transfusion. OBJECTIVE: To determine whether administration of IVIG to newborns with significant hyperbilirubinemia due to ABO hemolytic disease would reduce the need for exchange transfusion as a primary goal in these babies. DESIGN: This was a prospective study involving all newborns with significant hyperbilirubinemia due to direct Coombs-positive ABO hemolytic disease. METHODS: All healthy term babies with ABO hemolytic disease with positive direct Coombs test in the period between 2000 and 2002 were identified. Significant hyperbilirubinemia was defined as hyperbilirubinemia requiring phototherapy and/or rising by 8.5 micromol/l per h (0.5 mg/dl per h) or more to require exchange transfusion. Babies were randomly assigned into two groups: group 1 (study group) received phototherapy plus IVIG (500 mg/kg); and group 2 (control group) received phototherapy alone. Exchange transfusion was carried out in any group if at any time the bilirubin level reached 340 micromol/l (20 mg/dl) or more, or rose by 8.5 micromol/l per h (0.5 mg/dl per h) in group 2. RESULTS: A total of 112 babies were enrolled over 2 years, 56 in each group. Exchange transfusion was carried out in four babies in the study group, while 16 babies in the control group required exchange. Late anemia was not of concern in either group. No adverse effects related to IVIG administration were recorded. CONCLUSION: Administration of IVIG to newborns with significant hyperbilirubinemia due to ABO hemolytic disease with positive direct Coomb's test reduces the need for exchange transfusion without producing immediate adverse effects.

ABO Blood-Group System↗
PubMed1965

AUTOIMMUNE DISEASE IN NZB/BL MICE. I. PATHOLOGY AND PATHOGENESIS OF A MODEL SYSTEM OF SPONTANEOUS GLOMERULONEPHRITIS.

This study, based upon 528 laboratory examinations and 16 complete autopsies of NZB/Bl mice, deals with autoimmune manifestations (as shown by hypergammaglobulinemia, Coombs positive hemolytic anemia, and the occasional presence of lupus- and rheumatoid-like factors) and mainly with the pathology and the pathogenesis of glomerulonephritis in these mice, a model system of membranous glomerulonephritis with spontaneous and insidious onset, progression through chronic stages, and almost certainly induced by immunological, and autoimmune, mechanisms. The earliest and lasting histological change was hyaline thickening of the capillary walls and adjacent intercapillary regions of the glomerular tufts, corresponding in location to polysaccharide-rich capillary basement membrane and mesangial materials. Distributed focally and diffusely in the glomerular tuft and eventually sparing no glomerulus, hyaline, granular, and fibrillar ("spongy fiber") materials produced narrowing of capillary lumens by concentric or eccentric encroachment upon them. In the later stages hyaline lobulation and sclerosis of the glomerular tufts occurred. Thus the lesions corresponded to those seen in human focal and diffuse membranous, chronic lobular, and lastly (intracapillary) sclerosing glomerulonephritis. In all instances of glomerulonephritis the glomerular tufts contained selective localizations of mouse immunoglobulins corresponding in distribution to that of the hyaline and (PAS-positive) polysaccharide-rich materials in the focal and diffuse membranous and lobular lesions and in amounts increasing with the severity of glomerular disease. The mouse immunoglobulins were extracted from frozen sections of glomerulonephritic kidneys and were then capable of recombination with glomerular tufts in sections of autologous or isologous glomerulonephritic kidneys from which in vivo localized immunoglobulins had been extracted. The pattern of recombination with glomerular tufts was similar to that of in invo localized immunoglobulins. The extracted immunoglobulins did not show affinity for mouse red cells (in the indirect Coombs test) nor for autologous or isologous cell nuclei (in the immunofluorescence test). The serum of mice with severe glomerulonephritis contained immunoglobulins with in vitro affinity for extracted autologous or isologous glomerular tufts. Thus circulating as well as localized antibodies were demonstrated. The immunogenic materials (autoantigens) may have been formed in the glomerular tufts or accumulated in them from some other source, such as the circulating plasma; however they corresponded in location to polysaccharide-rich capillary basement membrane and mesangial materials. The spleen was identified at the cellular level as the main site of formation of autoantibodies to red cells, as well as the main site of red cell destruction. Some evidence was brought forth suggesting that these autoantibodies were "heavy" or gammaM-globulins. More studies are in progress.

Animals↗
PubMed1993

[Antibody detection after antepartal rhesus prophylaxis: normal values or sensitization].

Antibody screening tests were performed in 29 unsensitized pregnant women after antepartum Rh immune prophylaxis, using the indirect Coombs test (ICT) and a more sensitive ID-microtyping-system (IDM). With the ICT, anti-D antibodies were detected in 85% for at least 4 weeks and at most 8 weeks after immunisation. The maximum titer was 1:8. With the IDM, 97% showed antibodies against 'D' for at least 4 weeks and at most 11 weeks with a maximum of 1:16. The IDM titer was always 1 to 3 steps more sensitive than the ICT. After postpartum Rh immune prophylaxis, anti-D titers were again positive in many of the patients (ICT: 42%; IDM: 60%). In conclusion, it is nearly always possible to measure antibodies against 'D' after antepartum Rh immune prophylaxis and IDM was superior in comparison to ICT. However, maternal isoimmunisation to the rhesus antigen cannot be excluded for sure and patients have then to be controlled. As isoimmunisation could not be confirmed in any of our patients, postpartum Rh immune prophylaxis has to be administered even after detection of an antibody titer against 'D' after antepartum Rh prophylaxis.

Coombs Test↗
PubMed1984

Propylthiouracil-associated hemolytic anemia, thrombocytopenia, and antinuclear antibodies in cats with hyperthyroidism.

Nine of 105 cats with hyperthyroidism treated with propylthiouracil developed a serious immune-mediated drug reaction during treatment. Adverse clinical signs, which developed after 19 to 37 days (mean, 24.8 days) of propylthiouracil administration, included lethargy, weakness, anorexia, and bleeding diathesis. Physical examination revealed pale mucous membranes, and petechial hemorrhages of the skin and oral cavity. Results of hematologic testing revealed severe anemia and thrombocytopenia. The direct antiglobulin (Coombs') test was positive in all 7 cats evaluated, whereas the serum antinuclear antibody titer was greater than or equal to 1:10 in 5 of the 8 cats tested. In 4 of the cats, treatment included appropriate supportive therapy and cessation of propylthiouracil; in these cats, anemia and thrombocytopenia resolved and Coombs' and antinuclear antibody tests became negative within 2 weeks.

Anemia, Hemolytic↗
PubMed1995

Natural killer cell lymphoproliferative disorder of granular lymphocytes presenting as hemolytic anemia: case report and review of the literature.

Lymphoproliferative disorders of granular lymphocytes (LDGLs) have recently been hypothetically defined based on their immunophenotype, function, and clonality. The majority (129/161) of LDGLs are of the T-cell subset, which is typically associated with neutropenia and occasionally with anemia. The remainder (32/161) are of natural killer cell origin. This subset is associated with neutropenia (52% of cases) and anemia (60% of cases). The anemia most often has no immediately apparent cause. The Coombs test was negative in all cases reported. There is only one reported case of an associated Coombs-negative hemolytic anemia. We report an unusual case of natural killer cell LDGL, defined by morphology and immunophenotypic analysis, presenting as a de novo Coombs-negative hemolytic anemia. The anemia was resistant to steroid therapy. Therapeutic splenectomy resulted in a temporary resolution of the hemolytic process. The splenic pathology is also described.

Aged↗
PubMed1992

Evaluation and treatment of jaundice in the term newborn: a kinder, gentler approach.

Standard recommendations for evaluating and treating jaundice in term babies include following all babies closely for jaundice, obtaining several laboratory tests in those with early jaundice or bilirubin levels more than 12 to 13 mg/dL (205 to 222 mumol/L), using phototherapy to try to keep bilirubin levels below 20 mg/dL (342 mumol/L), and doing exchange transfusions if phototherapy fails, regardless of the cause of the jaundice. These recommendations are likely to lead to unnecessary testing and treatment of many jaundiced term infants. Because most jaundiced infants have no underlying illness, and the generally recommended laboratory tests lack sensitivity and specificity, they are seldom useful. In most babies, the only blood tests needed to evaluate jaundice are the blood type and group (of baby and mother) and a direct Coombs' test. A determination of direct bilirubin level should be added if jaundice is prolonged (greater than 2 to 4 weeks) or the baby has other signs of illness. Bilirubin toxicity is rare in term babies without hemolysis. In this low-risk group, the risks and cost of identifying and treating high bilirubin levels may exceed the benefits. Such infants need not be closely followed for jaundice. If significant jaundice is nonetheless found, treatment should be deferred to relatively high levels of serum bilirubin, with a goal of keeping bilirubin levels below 400 to 500 mumol/L (23.4 to 29.2 mg/dL). Babies with hemolytic disease should be followed more closely, and their bilirubin levels kept below 300 to 400 mumol/L (17.5 to 23.4 mg/dL). These recommendations should be reevaluated as new data become available. In the meantime, currently available data justify an approach to the jaundiced term infant that is less aggressive than previously recommended.

Bilirubin↗
PubMed1984

Positive direct antiglobulin tests and immune hemolytic anemia in patients receiving procainamide.

To characterize the autoimmune phenomena in patients receiving procainamide, we studied the prevalence of positive direct antiglobulin (Coombs') tests and immune hemolytic anemia in 100 such patients and compared them with 100 age-matched and sex-matched controls. There was a significant increase in the frequency of positive direct antiglobulin tests in patients receiving procainamide (21 vs. 10 per cent, P = 0.05). The mechanism of red-cell sensitization in patients receiving procainamide was the production of red-cell autoantibody, which was serologically indistinguishable from that seen in warm autoimmune hemolytic anemia. In contrast, positive direct antiglobulin tests in control patients were due to the presence of complement components. Red-cell autoantibody production secondary to procainamide was not correlated with a higher-than-expected frequency of antinuclear antibodies or the clinical syndrome of drug-induced lupus erythematosus. In the series of 100 patients receiving procainamide, we identified three cases of immune hemolytic anemia. In two of the three cases, the anemia resolved after the medication was discontinued and did not require steroid therapy. We conclude that procainamide often results in the production of red-cell autoimmune phenomena.

Aged↗
PubMed1968

Significance of Rh-sensitization during pregnancy: its relation to a preventive programme.

A study of the incidence of Rh-sensitization showed a 6.5% incidence of anti-D appearing for the first time during the last trimester of pregnancy. In 24 of the 29 subjects these antibodies were weak, and were found only when a sensitive technique using enzyme-treated Rh-deletion test cells was employed. The remaining five, however, had high-titre antibodies, which were associated with a positive Coombs test on cord blood.Rh-immune globulin administered at delivery resulted in disappearance of the anti-D in all but one of the subjects with weak antibody to whom it was given, suggesting that this treatment can reverse early sensitization. There was no effect when Rh-immune globulin was given to one subject with a high anti-D titre.Since sensitization has been found to occur frequently during the last trimester of pregnancy, an antenatal schedule of prophylaxis is advocated.

Antibody Formation↗
PubMed1981

Existence of the natural antibody against human-gamma-globulin in bovine sera.

The natural antibody against human gamma-globulins has been found in 2 out of 26 bovine sera. The bovine sera were absorbed with human erythrocytes of group O and tested with human red cells coated with incomplete antibodies. Two of 26 sera studied displayed evident agglutinating properties similar to those of anti-human globulin used in Coombs test.

Animals↗
PubMed1975

[Aggregate-hemagglutination test for anti-erythrocyte antibodies].

A new test for detection of antierythrocyte antibodies is described; one of its variants is three orders of magnitude more sensitive than the classic Coombs test. The proposed procedures are based on the agglutination of the red blood cells following addition of test-erythrocytes coated with the aggregated proteins of an antiglobulin serum. Results of application of the technique for diagnosis of the autoimmune hemolytic anemia showed its high specificity and the absence of prozone phenomenon.

Anemia, Hemolytic, Autoimmune↗
PubMed1983

Immune disorders in agnogenic myeloid metaplasia: relations to myelofibrosis.

Tests for a dysimmune state were done in an unselected group of 67 patients with agnogenic myeloid metaplasia (AMM). The results were compared to those of 56 patients with polycythaemia vera (PV). 75% of AMM patients versus 32% of PV patients had various abnormalities. The most frequent disorders among AMM patients were serum antinuclear and anti smooth muscle autoantibodies (10.3% each), a positive test for rheumatoid factor (21.7%), a polyclonal increase in serum immunoglobulin levels (46.8%) or a serum monoclonal component (9.7%), a positive direct Coombs' test (19%), an anti I autoantibody (30%). In AMM patients there was no relationship between age, sex, importance of splenic enlargement, time from diagnosis or treatment and the present of a dysimmunity. Furthermore, in AMM patients, but also in PV patients, it seems that the more frequent and numerous these abnormalities the more severe is the myelofibrosis. Like other previous studies, these results suggest a lymphoid cell involvement in AMM and a role for these immune disorders in the pathogenesis of myelofibrosis.

Adult↗
PubMed1992

[Diagnosis of brucellosis in an endemic area. Evaluation of routine diagnostic tests].

BACKGROUND: The use of classic methods of diagnosis of brucellosis was analyzed, particularly serologic methods whose use in endemic areas and risk groups has been questioned in the literature. METHODS: Prospective analysis of these methods was performed in a group of 171 patients suspected as having brucellosis proceeding from an endemic area, with progressions of risk and frequent antecedents of brucellosis. The results obtained were compared in 119 patients in whom brucellosis was confirmed (80 with positive cultures and 39 with clinic-serologic diagnosis) and in 52 in whom the diagnosis was excluded. RESULTS: The hemocultures provided a sensitivity of 70% with a mean delay in growth of 13.6 days. The rise of Bengal test showed sensitivity of 95% and specificity of 75%. The most adequate cut-off point for seroagglutination was of 1/160 and for the Coombs test 1/320 with sensitivities of 93 and 92% and specificities of 97 and 100%, respectively. CONCLUSIONS: The routine serologic tests offer good results for the diagnosis of brucellosis in endemic areas upon use of adequate cut-off points and permitting therapeutic decisions to be taken prior to knowledge of the results of the cultures. The rose of Bengal test is valid for initial selection of this type of population.

Adolescent↗
PubMedDate not supplied

Serologic diagnosis in the differentiation of autoimmune hemolytic anemias.

A complex serologic study was carried out in 20 patients with autoimmune hemolytic anemias (AIHA). The methods used were: the direct Coombs' test with specific sera anti IgG, IgM, IgA and complement (C), the direct and indirect test with papain treated erythrocytes (at 37 degrees C), determination of cold agglutinin titer and of warm and cold hemolysins. By these investigations using indigenous sera, the 20 cases of autoimmune hemolytic anemia could be classified: a) according to the thermal behaviour of autoantibodies, into warm antibody AIHA -- 15 cases, cold antibody AIHA -- 2 cases and both warm and cold antibody AIHA -- 3 cases; and b) according to the sensitizing globulin, into: IgG type -- 10 cases, IgG + C type -- 7 cases, IgG + IgM + C type -- 1 case, type C + cold agglutinins -- 2 cases.

Agglutination Tests↗