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Immune haemolytic anaemia associated with ampicillin dependent warm antibodies and high titre cold agglutinins in a patient with Mycoplasma pneumonia.

A case of severe immune haemolytic anaemia in a 54-year-old man suffering from Mycoplasma pneumonia is presented. A strongly positive direct Coombs test with erythrocyte bound IgG, C3d and C4 was demonstrated during the haemolytic process. Further, serologic investigations revealed ampicillin-dependent 'warm' antibodies and a cold agglutinin titre greater than 2000. No firm conclusion can be drawn as to which antibody caused the haemolysis. Treatment including withdrawal of antibiotics, blood transfusions (washed red cells, concentrated erythrocyte suspension) and corticosteroids was successful. It is suggested that tests should be carried out for erythrocyte bound drug-induced antibodies in cases of haemolysis with a history of drug exposure.

Agglutinins↗

IgG-mediated haemolysis masquerading as cold agglutinin-induced anaemia complicating severe infection with mycoplasma pneumoniae.

Haemolytic anaemia complicating Mycoplasma infection has usually been attributed to IgM cold agglutinins. This report describes a patient with pneumonia due to Mycoplasma pneumoniae in whom severe haemolysis persisted despite declining thermal amplitude and titre of cold agglutinins as the infection resolved. Class-specific anti-globulin (Coombs) testing defined an IgG warm agglutinin coating the patient's erythrocytes that was distinct from the IgM cold agglutinin identified by Sephadex G-200 gel filtration and dithiothreitol inactivation. Monoclonal IgM(gamma) and IgK(k) circulating proteins were identified and immuno-electrophoresis of the cold agglutinin-containing cryoglobulin fraction identified the cold agglutinin as an IgM(gamma). In this patient initially presumed to have cold agglutinin induced haemolysis secondary to Mycoplasma infection, an IgG warm agglutinin was identified as the aetiology for the patient's haemolysis, underscoring the clinical relevance of careful evaluation of the mechanism of haemolysis accompanying Mycoplasma pneumonia.

Agglutinins↗

Venous thrombosis associated with lupus anticoagulant and anticardiolipin antibodies.

We describe deep vein thrombosis associated with lupus anticoagulant and anticardiolipin antibodies in three children aged 10 to 14 years. One of them also had arterial thromboses. None of the patients had systemic lupus erythematosus when the thrombosis first occurred, but one fulfilled the criteria for systemic lupus erythematosus 3 years later. At presentation all had symptoms suggestive of pulmonary embolism and evidence of an autoimmune disease: Addison's disease in one, anti-DNA or antinuclear antibodies in all three, and a positive Coombs' test in two. Two of the three gave a false-positive test for syphilis. In the patient with systemic lupus erythematosus recurrent thrombocytopenia and severe haemolytic anaemia necessitated splenectomy. A child should be tested for lupus anticoagulant or anticardiolipin antibody if venous or arterial occlusion occurs without a known predisposing cause, or if there is pulmonary embolism or symptoms or laboratory findings suggestive of a connective tissue disease.

Adolescent↗

Thrombo-ischaemic pinnal necrosis associated with fenbendazole treatment in a dog.

An 11-week-old, female West Highland white terrier was presented with necrosis of the distal third of both pinnae. Haematology, biochemistry and urinalysis, Coombs test, antinuclear antibody and cold autoagglutinin antibody tests were normal. A drug reaction to fenbendazole was diagnosed. The necrotic ear tips were surgically removed. Histopathology revealed extensive coagulative necrosis of the epidermis and superficial to mid-dermis, a moderate interstitial neutrophilic infiltrate and complete thrombotic occlusion and necrosis of blood vessels. There was also endothelial cell activation and proliferation with endothelial cell cushions protruding into the vascular lumen. Immunohistochemistry for factor VIII-related antigen confirmed endothelial cell involvement. This case represents an unusual, drug-induced, thrombo-ischaemic necrosis of the pinnae. It is also, to the authors' knowledge, the first report of fenbendazole sensitivity in a dog. The histopathology is similar to previous cases of proliferative thrombovascular pinnal necrosis, suggesting that drug reactions should be considered in this condition.

Animals↗

Erythrocyte pyruvate kinase deficiency in a beagle dog.

A macrocytic hypochromic anemia with marked reticulocytosis was observed at each of 10 examinations during a 4 month period of a male Beagle dog that was 11 months old when first examined. The owner had noticed pale mucous membranes from the time the dog was purchased at 7 weeks of age. Based on the clinical history and negative LE, ANA and Coombs tests, an intrinsic erythrocyte defect was suspected. Erythrocyte osmotic fragility and hemoglobin electrophoresis were normal. Autohemolysis of incubated erythrocytes was marked. Hemolysis was uncorrected by glucose but partially corrected by ATP. With the exception of pyruvate kinase (PK), all of the erythrocyte enzymes measured had greater activities than those of control Beagle erythrocytes. In comparison to moderately reticulocyte-rich controls. PK activity was low in the affected Beagle. Erythrocyte phosphoenolpyruvate content was increased significantly as expected in PK deficiency. The kinetic constant (Km) for phosphoenolpyruvate was lower than that of normal control dogs, a finding in agreement with studies of PK from deficient Basenjis. On these bases a diagnosis of PK deficiency was made.

Journal Article↗

Cyclophosphamide exerts no beneficial effect over prednisone alone in the initial treatment of acute immune-mediated hemolytic anemia in dogs: a randomized controlled clinical trial.

Cyclophosphamide is commonly used with prednisone in the initial treatment of severe idiopathic immune-mediated hemolytic anemia (IMHA) in dogs because retrospective reports suggest its benefit. This randomized controlled prospective clinicaltrial evaluated whether combined cyclophosphamide and prednisone therapy is more efficacious than prednisone therapy alone in the initial treatment of IMHA. Eighteen dogs with acute, severe idiopathic IMHA were randomly assigned to 1 of 2 treatment groups. The P group received prednisone therapy alone (1-2 mg/kg PO q12h), and the PC group received prednisone (1-2 mg/kg PO q12h) and cyclophosphamide (50 mg/m2 PO q24h for 4 consecutive days a week) for 4 weeks. The mortality rate in the P group was 20% (2 of 10), and in the PC group, the mortality rate was 38% (3 of 8). There was no difference in sequential CBC evaluations between the 2 groups. However, whereas dogs in the P group showed increases in reticulocyte count, reticulocytosis was suppressed in dogs in the PC group during the 1st week of therapy. Spherocytosis resolved more quickly in the P group (day 21) than in the PC group (day 28), but the time taken to achieve a negative Coombs' test result was comparable between groups. No difference was observed in the volume of packed red blood cells (pRBCs) given per transfusion between treatment groups, but more dogs in the PC group required a 2nd transfusion. The results of this limited study suggest that cyclophosphamide plus prednisone has no benefit over prednisone alone in the initial treatment of acute, severe idiopathic IMHA indogs.

Acute Disease↗

Some serological reactions to "brucella" antigen in the horse.

Seventy-three samples of serum, from 69 horses and one zebra, were subjected to the Rose Bengal Plate, serum tube agglutination, complement fixation, and anti-equine globulin (Coombs') tests for brucellosis. Fifty-one of the samples, from 48 horses, were submitted by practising veterinary surgeons; of these, 22 samples were associated with clinical conditions which might have been due to brucellosis. Fourteen samples were from healthy horses known to have been in contact with infected cattle, and six were from horses which were known not to have been exposed to brucellosis. More reactions at accepted diagnostic levels were obtained to the anti-globulin and complement fixation tests than to the agglutination test. Two horses showed no reactions, other than inconclusive titres to the antiglobulin test, and these titres could have resulted from exposure to Brucella. Eight of nine positive Rose Bengal tests were confirmed by a reaction at diagnostic level in at least one of the other tests, but two sera showing a reaction at diagnostic level to the other tests gave a negative Rose Bengal result.

Agglutination Tests↗

Cefamandole therapy in anaerobic infections.

Thirty-one adult patients with infections due to anaerobic bacteria were treated with cefamandole. Bacteroides fragilis group (17) and Bacteroides melaninogenicus (13) were the most frequent anaerobes isolated. Duration of therapy varied from 2 to 49 days. Results were judged satisfactory in 26 cases, and unsatisfactory in 1 case. Four cases could not be evaluated. Adverse reactions occurred in 16 patients and included positive direct Coombs' test without hemolysis, transient liver function abnormalities, phlebitis, reversible neutropenia, fever, eosinophilia, and toxic epidermal necrolysis. The more significant reactions were associated with prolonged therapy. None was lethal. These data suggest that cefamandole is effective in treatment of most anaerobic infections.

Adult↗

Pharmacokinetics and safety of cefamandole in newborn infants.

Cefamandole, a new parenteral cephalosporin antibiotic, was administered to 23 newborn infants with pustular skin infection due to Staphylococcus aureus for an average duration of 7.5 days. All the patients improved clinically. Elevation of serum glutamic oxaloacetic transaminase and eosinophilia were observed in nine infants each transiently during treatment. There were no abnormalities of renal functions and Coombs' test results remained negative. The levels of cefamandole in serum after either intravenous or intramuscular administration were higher and the mean life was longer than those previously reported in older infants, children, and adults.

Cefamandole↗

Clinical trial of cefonicid for treatment of skin infections.

Twenty patients with skin and soft-tissue infections were treated with parenteral cefonicid. Cultures obtained in cellulitis cases from an aspirate of a leading edge of inflammation were positive in 42% of these patients. Pathogens isolated were Staphylococcus aureus (six strains), Proteus mirabilis (one strain), and Streptococcus agalactiae. Adverse effects were pain on intramuscular injection (two patients), rash (one patient), and positive Coombs test (one patient). All side effects were mild and none required discontinuing antibiotic therapy. A single treatment failure occurred in a patient with an undrained perirectal abscess. Cefonicid may be a useful drug in the treatment of skin and soft-tissue infections. The long half-life of cefonicid (4.8 h) is a valuable advantage and may facilitate patient compliance and convenience.

Adult↗

Cephacetrile: clinical evaluation in 27 patients.

Cephacetrile, a new derivative of 7-aminocephalosporanic acid, was evaluated in 27 patients. Soft tissue infections due primarily to gram-positive cocci were treated in 16 patients; 12 had bacteriological and clinical cure, and 4 improved but the lesions resolved incompletely or cultures remained positive. Seven of eight patients with respiratory tract infections were cured, including three with pneumococcal pneumonia; the eighth proved to have a noninfectious process and failed to respond. Two patients with acute urinary tract infections due to Escherichia coli had prompt clinical and bacteriological improvement, but follow-up was incomplete. One patient with sepsis due to Staphylococcus aureus expired. Laboratory abnormalities observed during cephacetrile therapy included mild eosinophilia in four patients, thrombocytosis in nine, direct Coombs' test positivity in four, and an elevated serum glutamic pyruvic transaminase in eight patients. No evidence of nephrotoxicity was detected. Severe superinfection due to Enterobacter species was observed in one patient. Mean peak serum concentrations of cephacetrile were 22, 69, and 104 mug/ml after 1 g intramuscularly, 1 g intravenously, and 1.5 g intravenously, respectively. Thus, in early studies cephacetrile was efficacious for selected bacterial infections, but determination of its comparative value within the cephalosporin group of antibiotics requires further clinical investigation.

Bacterial Infections↗

Characterization of anemia induced by avian osteopetrosis virus.

Chickens infected intravenously at 8 days after hatching with an avian osteopetrosis virus developed a severe, progressive anemia in the absence of osteopetrosis. The anemia was characterized as a pancytopenia, in which erythrocytes, granulocytes, and thrombocytes decreased concomitantly. Serum bilirubin levels were normal, whereas erythrocytes from infected chickens demonstrated a slightly elevated osmotic fragility. A negative Coombs test indicated that there was no evidence for erythrocyte-bound antibody. Erythrocytes from infected animals had slightly decreased 51Cr-labeled erythrocyte survival time when compared with normal. Examination of marrow histological preparations, together with ferrokinetic studies with 59Fe, indicated that marrow failure occurred during the acute phase of the anemia. Circulating virus was present during the development and acute phases of the anemia, but disappeared during the recovery phase of the disease. Neutralizing antibody appeared after the disappearance of circulating virus. It is concluded that virus infection induced both marrow failure (aplastic crisis) and decreased erythrocyte survival.

Alpharetrovirus↗

Brucellosis treated with rifampicin.

14 children, aged between 15 months and 14 years, with brucellosis were treated with oral rifampicin only (20 mg/kg per day) for 3 weeks. Laboratory diagnosis depended on blood culture (positive for Brucella melitensis in 11 of the cases), serum agglutination, complement-fixation test, and Coomb's test. Response was good in each child, with fever clearing between the 2nd and 8th day. 2 children relapsed, but one relapse was probably a reinfection from contaminated cheese. Both children were given a further course of treatment (rifampicin and co-trimoxazole) which was successful. Despite the reasonably good results with rifampicin alone, it is advisable to combine the drug with co-trimoxazole when treating brucellosis.

Adolescent↗

Thrombosis in systemic lupus erythematosus: a French collaborative study.

A retrospective study was undertaken of 120 children with systemic lupus erythematosus (SLE) seen in Paris and its immediate suburbs who fulfilled at least four of the American College of Rheumatology diagnostic criteria for SLE, and in whom the disease was diagnosed before the age of 16 and between January 1975 and December 1987. Eleven of these children (eight girls and three boys) all more than 10 years of age (mean follow up 8.1 years; range 3-13) had thrombotic episodes (9%). Thrombosis was one of the presenting signs in seven patients; in five it was associated with typical symptoms of SLE, and in the other two the thrombotic episode was isolated and diagnosis of SLE was delayed one and three years. Of a total of 16 thrombotic episodes (six of which were recurrent), 14 involved the leg veins, and in four there was associated pulmonary embolism. There were two episodes that affected cerebral arteries. The American College of Rheumatology diagnostic criteria for SLE as well as the incidence of lupus anticoagulant, positive direct Coombs test, and vasculitis in this group of patients was compared with the incidence in patients with SLE but no thrombosis. Only lupus anticoagulant was significantly associated with thrombotic episodes: eight of 11 (73%) of patients with SLE and thrombotic (arterial or venous) episodes had lupus anticoagulant compared with only 10 of 74 patients (14%) with no history of thrombotic events in the same age group.

Adolescent↗

Splenectomy for refractory Evans' syndrome associated with antiphospholipid antibodies: report of two cases.

The main haematological manifestations seen in patients with antiphospholipid antibodies (aPL) are thrombocytopenia, usually mild, and haemolytic anaemia with a positive Coombs test. Owing to the shared characteristics with idiopathic thrombocytopenic purpura, similar rules are followed in the treatment of these cytopenias. Two patients with severe aPL associated cytopenias, who required splenectomy after being refractory to steroids, immunosuppressive agents, and other treatments (intravenous gammaglobulin, danazol), are described, and previously reported cases are reviewed.

Adult↗