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Immunosuppression in dogs by pretransfusions with ultraviolet (UV)-irradiated whole blood.

Ultraviolet (UV)-irradiated whole dog blood prevented the initiation of proliferative responses in allogeneic mixed lymphocyte reactions (MLR). When dogs were given 4 weekly intravenous transfusions of UV-irradiated allogeneic donor whole blood, peripheral blood lymphocytes (PBL) of the recipients responded less significantly to donor PBL in MLR for over one week after the final transfusion. Red blood cell (RBC)-crossmatching of these dogs was negative. Dogs treated with UV-irradiated blood did not produce anti-donor PBL antibody, or IgG, IgM and C3 determined by the indirect Coombs test. These dogs also had negligible delayed type hypersensitivity (DTH) responses to donor PBL at the end of the treatment period, recognized as slightly suppression of skin graft rejection. In contrast, six dogs receiving injections of untreated allogeneic whole blood evidenced high proliferation in MLR, agglutination in RBC-crossmatching, acute rejection of skin grafts and three of them produced C3 in the Coombs test.

Animals↗

Thrombotic thrombocytopenic purpura associated with systemic lupus erythematosus.

Thrombotic thrombocytopenic purpura (TTP) occurring in patients with systemic lupus erythematosus (SLE) is rare and can be difficult to diagnose because of overlapping features of the two disorders. The aim of this study is to further characterize this uncommon association in terms of presenting features, diagnostic difficulties and treatment outcome. This is the largest series from a single centre with 6 patients diagnosed over a 6-year period. Two thirds of the patients had a simultaneous diagnosis of TTP and SLE. Half of the patients had a positive Coombs test along with clear features of TTP. Five patients received plasmapheresis as initial treatment while 1 patient received plasma infusions only. Four out of 5 patients responded to plasmapheresis and only 1 patient required cytotoxic therapy. TTP in association with SLE appears to be underdiagnosed and a positive Coombs test is not against the diagnosis of TTP in this setting. Most of the patients respond well to plasmapheresis. In case of a poor response, cytotoxic drugs should be considered early.

Adolescent↗

Cold hemagglutinin disease in the operating room.

Cold hemagglutinin disease is infrequently recognized before complications ensue. We describe a patient with chronic cold hemagglutinin disease who sustained an acute hemolytic crisis during a routine operative procedure in a cool operating room. Cold agglutinins were present during routine preoperative blood cross matching with the Coombs' test positive for C3d. Analysis of the offending cold agglutinin revealed a high-titer monoclonal IgM-kappa antibody with anti-I specificity and broad thermal amplitude. Major complications from the presence of cold agglutinins have been poorly documented and are often thought to be of only theoretic concern. This case and literature review show that such complications may occur and emphasize the importance of careful preoperative plans when the Coombs' test suggests that cold agglutinins exist.

Aged↗

[Aspects of humoral immunity in ulcerous colitis].

Various immunological indices, hitherto considered in isolation, were evaluated in a single group of 20 cases of ulcerous colitis. Immunofluorescence showed anticolon Ab in 3 cases (15%), whereas this features was absent in a control group. Antistomach, antithyroid and non-organ-specific Ab's (ANA, AMA, SMA) were equally incident in both groups. One caso is examined separately on account of its simultaneous presentation of human and rat antistomach and antithyroid and antismooth muscle Ab's. Reuma test, Waaler Roose reaction, L.E. phenomenon and test, and direct and indirect Coombs test results were negative in nearly all cases. Slight quantitative changes in serum proteins revealed by electrophoresis and immunodiffusion were indicative of inflammation with an immunitary tendency. The data are not sufficient to support the attribution of an autoimmunitary aetiology to ulcerous colitis, though simultaneous evaluation of reaction indices serves to strengthen this view.

Adolescent↗

Multiple autoantibody production in a patient with splenic lymphoma.

We report on a patient with splenic lymphoma of B-cell origin who developed autoimmune hemolytic anemia (AIHA). IgM lambda M-protein, IgM anticardiolipin antibody (ACA), and lupus anticoagulant (LA) were detected in the serum, and direct Coombs' test showed autoantibodies of the IgG1 and IgG2 subclasses on red blood cells (RBC). In in vitro culture, tumor cells isolated from the spleen produced only IgM ACA, which was enhanced by IL-6 but not by IL-4 or IL-5. The levels of ACA and LA decreased after splenectomy and chemotherapy; the strength of the direct Coombs' test, however, did not change. These findings indicated that in this patient the lymphoma cells produced IgM lambda ACA, but not autoantibodies of the IgG1 and IgG2 subclasses against RBC. It was also suggested that IL-6 might at least partially stimulate the production of ACA.

Anemia, Hemolytic, Autoimmune↗

Post-phototherapy neonatal bilirubin rebound: a potential cause of significant hyperbilirubinaemia.

AIM: To determine the incidence of post-phototherapy neonatal plasma total bilirubin (PTB) rebound. METHODS: A prospective clinical survey was performed on 226 term and near-term neonates treated with phototherapy in the well baby nursery of the Shaare Zedek Medical Center from January 2001 to September 2002. Neonates were tested for PTB 24 hours (between 12 and 36 hours) after discontinuation of phototherapy, with additional testing as clinically indicated. The main outcome measure, significant bilirubin rebound, was defined as a post-phototherapy PTB > or =256 micromol/l. Phototherapy was not reinstituted in all cases of rebound, but rather according to clinical indications. RESULTS: A total of 30 (13.3%) neonates developed significant rebound (mean (SD) PTB 287 (27) micromol/l, upper range 351 micromol/l). Twenty two of these (73%) were retreated with phototherapy at mean PTB 296 (29) micromol/l. Multiple logistic regression analysis showed significant risk for aetiological risk factors including positive direct Coombs test (odds ratio 2.44, 95% CI 1.25 to 4.74) and gestational age <37 weeks (odds ratio 3.21, 95% CI 1.29 to 7.96). A greater number of neonates rebounded among those in whom phototherapy was commenced < or =72 hours (26/152, 17%) compared with >72 hours (4/74, 5.4%) (odds ratio 3.61, 95% CI 1.21 to 10.77). CONCLUSION: Post-phototherapy neonatal bilirubin rebound to clinically significant levels may occur, especially in cases of prematurity, direct Coombs test positivity, and those treated < or =72 hours. These risk factors should be taken into account when planning post-phototherapy follow up.

Bilirubin↗

[Angioimmunoblastic T-cell lymphoma accompanied by pure red cell aplasia].

A 71-year-old woman was admitted in December 2002 because of lymphadenopathy, hepatosplenomegaly and pleural effusion. She had severe anemia with hemoglobin 5.9 g/dl and a reticulocyte count of 1% per hundred. Direct/indirect Coombs tests and anti-double stranded DNA antibody were positive, her serum CH50 level was reduced and an increase in serum LDH isoenzyme 3 was observed. Bone marrow aspiration showed an almost total absence of erythroblasts and no pathological cell proliferation. The diagnosis of angioimmunoblastic T-cell lymphoma (AILT) was made based on the lymph node histological findings. Proliferation of arborizing small vessels with hyperplastic endothelium and infiltration of atypical T-lymphocytes were observed. After combination chemotherapy (THP-COP), remission was achieved in both the pure red cell aplasia (PRCA) and AILT. Remission was also accompanied by normalization of the Coombs tests, suggesting that autoimmune mechanisms in AILT may contribute to the development of PRCA.

Aged↗

Long-term follow-up in 128 patients with primary antiphospholipid syndrome: do they develop lupus?

We retrospectively studied a large cohort of patients with primary antiphospholipid syndrome (APS) from 4 different referral centers to analyze the clinical and serologic features and, specifically, to determine the number of patients going on to develop systemic lupus erythematosus (SLE) or other autoimmune disease after long-term follow-up. The study included 128 unselected patients with primary APS who fulfilled the Sapporo International Criteria from 4 different tertiary hospitals in the United Kingdom, Mexico, and Spain. The patients had attended the referral centers between January 1987 and July 2001. We reviewed clinical and serologic characteristics according to a pre-established protocol. We used univariate analysis with the chi-squared or Fisher exact test and logistic regression to analyze possible factors related to the coexistence of SLE and APS. Ninety-seven female and 31 male patients fulfilled the criteria, with a median age of 42 +/- 12 years (range, 16-79 yr), and with a mean follow-up of 9 +/- 3 years (range, 2-15 yr). The main manifestations included deep vein thrombosis in 62 patients (48%), arterial thrombosis in 63 (49%) patients, pregnancy loss in 177/320 (55%) cases, and pulmonary embolism in 37 (30%) patients. Other clinical manifestations were migraine in 51 (40%) patients, thrombocytopenia in 48 (38%), livedo reticularis in 47 (37%), and valvular disease in 27 (21%). Serologic findings were anticardiolipin antibodies (aCL) IgG positive in 110 (86%) patients, aCL IgM in 36 (39%), lupus anticoagulant in 71 (65%), antinuclear antibodies in 47 (37%), and positive Coombs test in 5 (4%) patients. During the follow-up and after a median disease duration of 8.2 years (range, 1-14 yr), 11 (8%) patients developed SLE, 6 (5%) developed lupus-like disease, and 1 (1%) developed myasthenia gravis. The remaining 110 patients (86%) continued to have primary APS. After the univariate analysis, a family history of lupus, the presence of Raynaud phenomenon, migraine, psychiatric features, multiple sclerosis-like features, hemolytic anemia, low C3 and C4, and Coombs positivity conferred a statistically significant risk for the subsequent development of SLE (p < 0.05). Only the presence of Coombs positivity had statistical significance (odds ratio, 66.4; 95% confidence interval, 1.6-2714; p = 0.027) after the logistic regression evaluation. The current study confirms that progression from primary APS to SLE or lupus-like disease is unusual, even after a long follow-up. Only 3 patients developed anti-dsDNA antibodies. The presence of a positive Coombs test might be a marker for the development of SLE in patients with primary APS.

Abortion, Spontaneous↗

Rebound bilirubin levels in infants receiving phototherapy.

A retrospective medical record review was completed for 264 consecutive newborns receiving phototherapy for hyperbilirubinemia to determine whether a "rebound" increase in total serum bilirubin (TSB) level occurs after termination of phototherapy. The difference between mean TSB levels at discontinuation of phototherapy and at rebound was calculated by paired t test. TSB levels at rebound were significantly lower than at discontinuation of phototherapy for infants weighing > 1800 g (positive and negative Coombs' test results). There were no statistically significant differences among infants in the smaller weight categories, regardless of Coombs' test results. Infants completing phototherapy for hyperbilirubinemia who are otherwise healthy do not require follow-up solely to identify a rebound bilirubin level.

Bilirubin↗

The role of anticardiolipin autoantibodies in the pathogenesis of autoimmune hemolytic anemia in systemic lupus erythematosus.

OBJECTIVE: To elucidate the role of anticardiolipin antibodies (aCL) in the pathogenesis of hemolytic anemia in patients with systemic lupus erythematosus (SLE). METHODS: Immunoglobulins (Ig) and cardiolipin reactivity were evaluated in red blood cell (RBC) eluates and in the sera of patients with SLE and controls by a solid phase enzyme linked immunosorbent assay. RESULTS: aCL were detected in sera of 2 patients with SLE with active hemolytic anemia. The RBC eluates of these patients contained Ig (mainly IgG) with significant cardiolipin reactivity. RBC eluates from healthy volunteers failed to demonstrate measurable amounts of Ig whereas Ig eluted from RBC of chronic lymphocytic leukemia patients with active hemolysis but no aCL did not react with cardiolipin. Furthermore, under treatment, one patient went into complete remission with resolution of the hemolysis, negative Coombs' tests and lower serum aCL. The other patient, however, continued to demonstrate both high sera aCL and positive Coombs' tests. CONCLUSION: aCL may play a direct role in the pathogenesis of hemolytic anemia in some patients with SLE by acting as anti-RBC autoantibodies.

Adult↗

Localized CNS brucellosis: report of 7 cases.

Seven patients with brucellar infection localized in the central nervous system (CNS) are reported. This series represent 3.5% of all brucellosis cases in our hospital. There was a conspicuous absence of systemic signs and symptoms. The clinical course was characteristically protracted. Meningitis (acute, chronic, transient and recurrent) and progressive myeloradiculopathy were the 2 clinical patterns. Cranial nerve neuropathy was frequent, eight nerve involvement being present in 4 cases; transitory ischemic attacks and subarachnoid haemorrhage occurred in 2. Routine laboratory determinations were negative or non-specific. Cerebrospinal fluid (CSF) findings included hypoglycorrhachia, lymphocytic pleocytosis and hyperproteinorrhachia. There was also a remarkable increase in the gamma-globulin and IgG values with morphology of oligoclonal bands in CSF electrophoresis. Brucella agglutination titers were low or absent in serum and/or CSF. By contrast, Coombs tests were always positive and higher titers were found in serum and CSF. After treatment a persistent CSF positive Coombs test at low titers together with an isolated increase in CSF gamma-globulin and IgG values were detected in cured patients. Brucella blood cultures were negative, but CSF cultures were positive in four cases. Rifampin and doxycycline seems to be the treatment of choice. These agents must be maintained at least for 4 months in order to avoid relapses. Corticosteroids may be helpful at the beginning of treatment. Outcome is generally favourable in this disorder. We conclude that clinical and biological characteristics of localized CNS brucellosis are in accordance with those already described in other types of localized brucellosis.

Anti-Bacterial Agents↗

Isoimmunization is unlikely to be the cause of hemolysis in ABO-incompatible but direct antiglobulin test-negative neonates.

OBJECTIVE: It is stated that the direct antiglobulin (Coombs') test (DAT) may be negative in ABO hemolytic disease of the newborn. Thus, significant jaundice in neonates who are A-B incompatible with their mothers but DAT test negative is often attributed to isoimmunization and another diagnosis is not sought. We wished to determine the rate of bilirubin production, as an objective measure of hemolysis, in 2 groups of DAT-negative neonates--ABO-compatible and ABO-incompatible--and in DAT-positive ABO-incompatible neonates. METHODS: In consecutive, term, healthy newborns who were admitted to the general care nursery, we measured the level in parts per million (ppm) of end-tidal breath carbon monoxide (CO), corrected for inspired CO (ETCOc), an index of the rate of bilirubin production. We compared the levels in DAT-negative ABO-incompatible neonates with those in ABO-compatible neonates and with the levels in DAT-positive ABO-incompatible neonates. Statistical analysis was performed using 2-sample t and chi(2) tests. RESULTS: There was no significant difference between the mean 12-hour ETCOc levels in DAT-negative ABO-incompatible neonates (n = 60, 2.2 +/- 0.6 ppm) versus DAT-negative ABO-compatible neonates (n = 171, 2.1 +/- 0.6 ppm), although there was a difference between the mean levels in DAT-positive ABO-incompatible neonates (n = 14, 3.4 +/- 1.8 ppm) and the DAT-negative groups. Four DAT-negative ABO-incompatible neonates had elevated ETCOc levels; in 2, we diagnosed a specific hematologic abnormality, namely, glucose-6-phosphate dehydrogenase deficiency in 1 and elliptocytosis in the other. CONCLUSION: In DAT-negative newborns with significant jaundice or increased bilirubin production, even if ABO-incompatible, a cause other than isoimmunization should be sought.

Bilirubin↗

Development and clinical application of methods for detection of antineutrophil antibody in serum of the cat.

Two techniques, leukoagglutination and indirect immunofluorescence, were adapted to test for the presence of antineutrophil antibody in cat serum. The leukoagglutination test was analogous to an indirect Coombs' test. The test was performed on freshly isolated cat blood neutrophils, with the test results read from stained smears (Wright's stain) made from sedimented antiserum-treated neutrophils. A positive test response was indicated by agglutinated neutrophils on the stained smear. The indirect immunofluorescence test was performed by incubating paraformaldehyde-fixed cat blood neutrophils with test serum, after which the neutrophils were stained with fluorescein isothiocyanate-tagged antiglobulin. A positive test response was a ring of fluorescence surrounding the cells, as viewed through a UV microscope. Serum samples (n = 55) from clinically neutropenic cats were tested for the presence of antineutrophil antibody by the indirect immunofluorescence technique. Ten positive-control sera (rabbit anti-cat neutrophil serum) and 10 negative-control sera (normal cat serum) were included. Only the positive control sera exhibited neutrophil fluorescence, indicative of antineutrophil antibody. None of the 55 samples of clinical origin showed any appreciable fluorescence.

Agranulocytosis↗

A radiolabeled antiglobulin test for crossmatching platelet transfusions.

Despite the use of HLA-matched platelets for alloimmunized recipients, transfusion failures occur. In order to reduce these failures, we investigated the use of a radiolabeled antiglobulin technique for platelet crossmatching. The principle of the test is that of an indirect Coombs test using 125I labeled goat anti-human IgG. Incompatibility is determined by calculating a radioactivity antiglobulin test (RAGT) index. Using this technique, we performed 89 crossmatches on 19 leukemic or aplastic patients who were refractory to random donor platelets and receiving varying degrees of HLA-matched platelets. Effectiveness of the transfusion was assessed from the posttransfusion corrected platelet count increment (CCI) determined at 1 and 20 hr. When the RAGT index was 1.9 or less, the mean CCI at 1 lhr was 17,570 +/- 7003/cu mm, n = 55. When the RAGT index was 2.0 or greater, the mean CCI was 4237 +/- 4100/cu mm, n = 34. At 20 hr when the RAGT index was 1.9 or less, the mean CCI was 8722 +/- 3143/cu mm, n = 33, and when the index was 2.0 or greater, the mean CCI was 571 +/- 1286/cu mm, n = 23. Using this technique, one false negative resulted. Nine positive crossmatches with good increments at 1 hr were found; at 20 hr, however, the survival of these units was zero. These data suggest that this method is a useful adjunct in the selection of platelets in the refractory patient.

Adolescent↗

[Autoimmune hemolytic anemia complicating homozygotic beta- thalassemia].

Four cases of auto-immune hemolytic anemia complicating the course of intermediate or major beta-thalassemia syndromes are reported in children. Ages ranged from 2 to 13 years. Two children had undergone a splenectomy. The direct Coombs test was positive of the IgG +/- complement or complement alone type. Corticosteroid therapy was beneficial in the 3 children who were given this treatment. Coombs test became negative after intervals ranging from 15 days to 8 months.

Anemia, Hemolytic, Autoimmune↗

Significance of antibodies to cardiolipin in unselected patients with systemic lupus erythematosus: clinical and laboratory associations. The SLE Study Group.

In a multicentre study anticardiolipin antibodies of the IgG and IgM isotypes were measured by a solid phase enzyme immunoassay in 368 patients with systemic lupus erythematosus (SLE) who were not selected on the basis of features of antiphospholipid syndrome. Clinical and laboratory associations of increased levels of anticardiolipin antibodies were evaluated. IgG and IgM antibodies to cardiolipin were documented in 224 (60.9%) and 128 (34.8%) patients, respectively. Regarding the symptoms of antiphospholipid syndrome, elevated amounts of anticardiolipin IgG were significantly associated with spontaneous abortion (P < 0.001), thrombocytopenia (P < 0.01), livedo reticularis (P < 0.01) and a positive direct Coombs test (P < 0.05), but not with thrombosis or central nervous system diseases such as epilepsy and psychosis. IgM antibodies to cardiolipin were associated with a positive direct Coombs test (P < 0.01), but with no other symptom of antiphospholipid syndrome. The predictive values of anticardiolipin antibody determinations in unselected SLE patients were poor for all features of antiphospholipid syndrome because of high proportions of false-positive and false-negative results. As for other manifestations of SLE, positive correlations between raised antibodies to double-stranded DNA and the occurrence of anticardiolipin antibodies of the IgG isotype were observed, and anticardiolipin IgM was negatively associated with nephritis.

Adolescent↗

[Neonatal blood group incompatibility due to anti-M antibodies].

Neonatal blood group antagonism due to anti-M antibodies is extremely rare. The case is reported of a neonate with moderately severe haemolytic anaemia due to anti-M which required two blood transfusions. Although anti-M antibodies are as a rule regarded as clinically irrelevant, and although they react almost exclusively at lower temperatures, they may in exceptional cases be demonstrated at 37 degrees C, as in the patient described; they may then cause haemolysis. Most strikingly, the direct Coombs test in this patient was negative; this phenomenon has been described before. In unexplained haemolytic anaemia of a newborn, even in the presence of a negative direct Coombs test, the possibility of blood group antagonism should be considered.

Anemia, Hemolytic, Congenital↗

Characterization of the anemia of inflammatory disease in cats with abscesses, pyothorax, or fat necrosis.

The purpose of this study was to describe the anemia of inflammatory disease (AID) in cats with naturally-occurring inflammatory diseases, such as abscesses (n = 12), pyothorax (n = 6), and fat necrosis (n = 3). Exclusion criteria were positive FeLV/FIV tests, neoplasia, nephro-, hepato- or endocrinopathies, and blood loss anemia. CBC, clinical biochemistry, measurements of serum erythropoietin, iron, total iron-binding capacity (TIBC), ferritin, acute phase proteins, erythrocytic osmotic fragility (OF), and Coombs' tests were performed. A decrease in hematocrit of 1-28% (median, 10%) occurred within 3-16 days (median, 8 days). The anemia was mild (n = 11), moderate (n = 8), or severe (n = 2). In most cases it was normocytic normochromic, non-regenerative (n = 18), or mildly regenerative (n = 3). Sixteen cats had leukocytosis and 5 mild hyperbilirubinemia. The Coombs' test results were negative for 8 cats and positive for 1 cat. OF was increased in 2 out of 14 cats. Hypoalbuminemia (n = 18) and hyperglobulinemia (n = 16) resulted in a lowered albumin/globulin-ratio in 19 cats. Iron and TIBC were low in 2/19 and 6 /19 cats, respectively. The ferritin concentrations were normal in 7 cats and increased in 12 cats. The acute phase proteins alpha1-acid-glycoprotein and haptoglobin were increased in 14/14 and 13/14 cats, respectively. Erythropoietin was normal (n = 4), mildly increased (n = 7) or severely increased (1). Two cats were euthanized due to their underlying disease, 3 cats needed blood transfusions. AID in cats is usually mild to moderate, non-regenerative, and normocytic normochromic. It can be clinically relevant causing severe and transfusion-dependent anemia. AID seems to be multifactorial with evidence of iron sequestration, decreased RBC survival, and insufficient erythropoietin production and bone marrow response. Specific and supportive therapy, including transfusions, can reverse these processes.

Abscess↗