The low prevalence Rh antigen Be(a) (Rh36) is associated with RHCE*ce 662C>G in exon 5, which is predicted to encode Rhce 221Arg.

BACKGROUND AND OBJECTIVES: The low prevalence antigen, Be(a), is produced by a complex that also produces weak c, e and f (ce). We report here the molecular basis associated with Be(a) antigen expression. MATERIALS AND METHODS: Peripheral blood samples from four Be(a+) probands were tested. Haemagglutination, gDNA extraction, PCR-based assays, reticulocyte RNA isolation, Rh-cDNA analyses, and sequencing were performed by standard procedures. RESULTS: RBCs from Probands 1 and 3 were D-C-E-c+e+, and from Probands 2 and 4 were D+C+E-c+(W)e+. In proband 1, cDNA sequencing of RHCE revealed heterozygosity of nucleotide (nt) 662C/G in exon 5 of RHCE*ce. No other nucleotide changes were observed. As the 662C>G nucleotide change ablates a MscI restriction enzyme cleavage site, PCR-RFLP analysis was performed and the RHCE*ce nt 662C/G heterozygosity was detected on gDNA from the four probands and two children from both Proband 3 and Proband 4. CONCLUSION: The low prevalence Rh antigen, Be(a), is associated with a single nucleotide change in exon 5 of RHCE*ce; that of 662C>G and this change is predicted to alter proline at amino acid position 221 of Rhce to arginine. The fundamental differences in the properties of these two amino acids may impose a steric and/or charge-related effect on the protein, and thereby provide an explanation for the weakened expression of c, e and f (ce) antigens in the Be(a) phenotype.

Anti-basal ganglia antibodies and acute movement disorder following herpes zoster and streptococcal infections.

Anti-basal ganglia antibodies (ABGA) have been associated with poststreptococcal encephalitis similar to encephalitis lethargica (EL). We report two children with parainfectious encephalitis of similar phenotype and IgG ABGA. However, the associated pathogens in the two cases differed; beta-hemolytic streptococcus and herpes zoster. ABGA may not be specific to poststreptococcal encephalitis, but rather a surrogate marker of an inflammatory mediated movement disorder, which may respond to immunotherapy.

Diamond-blackfan anemia and cyclosporine therapy revisited.

A girl with Diamond-Blackfan anemia diagnosed in infancy started cyclosporine A (CSA) therapy at 9 years and 8 months of age after experiencing unacceptable side effects while receiving prednisone. Since then, she has been followed-up for more than 4 years. She exhibited a dramatic response to CSA, with weaning and then cessation of steroid therapy after 5 months. She has remained transfusion-independent. Attempts to discontinue CSA therapy have been unsuccessful. Relapse of the anemia has occurred in the context of viral infections with missed CSA doses. The major clinical problem during treatment has been recurrent oral aphthous ulceration, which responds to topical therapy. She is currently maintained on CSA 100 mg twice daily with a hemoglobin of 10.2 g/dL and a reticulocyte count of 1.6%. A trial of CSA therapy should be considered in patients with Diamond-Blackfan anemia in whom steroid therapy has failed before a transfusion program is instituted or alternative donor stem cell transplantation is entertained.

A population-based study of childhood myelodysplastic syndrome in British Columbia, Canada.

Myelodysplastic syndrome (MDS) is considered to be very rare in children. However, the only two published population-based studies reported widely divergent incidence figures. To further explore the epidemiology of childhood MDS and to evaluate the accuracy of cancer registry and treatment trial data, we conducted a population-based study of children aged 0-14 years in British Columbia (BC), Canada, between 1982 and 1996. MDS was diagnosed in 31 cases corresponding to an annual incidence of 3.2 per million children or 6% of all leukaemias, compared with an incidence of 6.0/million for acute myeloid leukaemia (AML), and of 0.5/million for chronic myeloid leukaemia. There was a non-significant (P = 0.19) trend toward an increase in MDS incidence with time, the increase was partly explained by an increasing number of patients with Down syndrome. Associated abnormalities were found in 48% of the MDS cases with Down syndrome as the most common (seven cases). Only one third of the MDS cases were correctly registered in the Cancer Registry and less than half of the eligible MDS patients were enrolled on a cooperative group study. Data on MDS from treatment-based studies and cancer registries were inaccurate and seemed to significantly underestimate the incidence of MDS in children.

The use of acute hemodilution in parturients undergoing cesarean section.

OBJECTIVE: Concern over transmissible disease has increased interest in methods of minimizing homologous blood transfusion during elective surgery. One method is acute hemodilution, a technique previously unreported in parturients. This study was designed to determine its feasibility and safety in women at risk of hemorrhage during cesarean section. STUDY DESIGN: This technique was performed on 38 parturients. Collected blood was retransfused at the end of surgery or earlier, if required. Hemoglobin was measured before hemodilution, after hemodilution, before transfusion, after transfusion, and 24 hours postoperatively. Neonatal assessment included umbilical blood gases and Apgar scores. RESULTS: All patients were hemodynamically stable and no fetal heart rate abnormalities were observed during the procedure. One patient received homologous blood and 14 received previously donated autologous blood. Umbilical blood gases were normal and 5-minute Apgar scores were > or = 7. CONCLUSION: This study suggests that acute hemodilution is well tolerated in parturients undergoing cesarean section. This may limit exposure to homologous blood transfusion.

Recombinant human erythropoietin for treatment of anemia of chronic disease in children with Crohn's disease.

We evaluated the efficacy and safety of and compliance with rH-EPO (150 U/kg three times a week subcutaneously for up to 12 weeks) for treatment of anemia in childhood Crohn's disease (n = 4). The mean hemoglobin level before rH-EPO therapy was 109 gm/L (10.9 gm/dl) (range, 103 to 115 gm/L). The mean hemoglobin level in the three compliant children increased to 138 gm/L (13.8 gm/dl) after treatment. Response time for the correction of anemia ranged from 6 to 12 weeks (mean, 9.5 weeks). Resolution of symptoms of lethargy, poor appetite, and irritability occurred with correction of the anemia. The only adverse effect observed was transient local pain at the injection site.

Pleural relapse during hematopoietic remission in childhood acute lymphoblastic leukemia.

PURPOSE: This report describes an isolated pleural relapse during hematopoietic remission in a child previously treated for acute lymphoblastic leukemia (ALL). PATIENT AND METHODS: An 11-year-old boy had a cough and exertional dyspnea 34 months after an initial diagnosis of ALL and 10 months after completion of therapy. Imaging studies revealed a large left pleural effusion. Bone marrow and cerebrospinal fluid studies were negative for disease at this time. RESULTS: Histopathologic examination of biopsy samples revealed cells with morphologic features of acute lymphoblastic leukemia blasts. Immunophenotyping, cytogenetic, and gene rearrangement studies confirmed the presence of a leukemic blast cell population similar to that detected at initial diagnosis. An isolated extramedullary relapse in the pleura was diagnosed. The patient underwent successful reinduction therapy and subsequently a matched unrelated donor bone marrow transplant; he died of disseminated infection in the posttransplant period. CONCLUSIONS: Unusual extramedullary sites of relapse are recognized with increasing frequency as long-term survival in childhood ALL improves. The length of the disease-free interval before relapse is felt to be of prognostic significance. Isolated relapse to the pleural space has not previously been described. The mechanism for persistence of leukemic clones in patients who appear to be in hematopoietic remission is unknown.

Incidence of iron-deficiency anaemia and depleted iron stores among nine-month-old infants in Vancouver, Canada.

The iron status and feeding practices of 434 infants in Vancouver were determined at 39 +/- 1 week of age. Iron-deficiency anaemia (haemoglobin < or = 101 g/L, or < or = 110 g/L with two or three abnormal results from tests of serum ferritin, zinc erythrocyte protoporphyrin and total iron binding capacity) occurred in 7% of infants. Low iron stores (serum ferritin < 10 micrograms/l) occurred in about 24% of infants. Iron-deficiency anaemia was significantly associated (p < 0.001) with duration of breastfeeding. The prevalence of iron-deficiency anaemia among infants breastfed for 8 months was 15%. At 39 weeks (9 months) of age, about 5% and 13% of the infants were bottle-fed with cows milk or low iron infant formula, respectively, and this was also significantly associated (p < 0.02) with low iron stores. Iron-fortified infant cereals had been introduced to 95% of the infants by six months of age. This study shows iron-deficiency anaemia is a problem among a significant number of nine-month-old infants in Canada, and is not explained by failure to introduce iron-fortified infant cereals.

Thrombotic thrombocytopenic purpura: a treatable cause of childhood encephalopathy.

We describe two patients less than 13 years of age with thrombotic thrombocytopenic purpura, a rare disorder in childhood. Both children were treated with plasma exchange therapy, which resulted in a rapid resolution of symptoms. This disorder is a cause of childhood encephalopathy, which can be treated effectively with plasma exchange.

A new method for characterization and epitope determination of a lupus anticoagulant-associated neutralizing antiprothrombin antibody.

A patient had both lupus anticoagulant hypoprothrombinemia syndrome and celiac disease. The presence of a neutralizing antiprothrombin antibody in the patient's serum was demonstrated by coagulation tests, immunoadsorption, and Western blot analysis. The probable cause for the severe hypoprothrombinemia was clearance of prothrombin-antibody complexes from the circulation. Studies showed the antiprothrombin antibody binding to human prothrombin was phospholipid- and Ca(++)-independent; the antibody did not bind to human thrombin. The target epitope of the antibody was studied by Western blot analysis of mutated recombinant human prothrombin molecules. The antibody reacted with the fragment 2-A region of prothrombin, spanning the second kringle domain and the thrombin A chain within prothrombin. Based on this new method, the proposed mechanism for the neutralizing action of the antibody is impairment of prothrombin activation by the prothrombinase complex, either by steric hindrance of the hydrolysis of prothrombin by factor Xa or by interference of the interaction of prothrombin with factor Va; both reactions are required for efficient conversion of prothrombin to thrombin.

Transient erythroporphyria of infancy.

We describe a neonate with hemolytic disease of the newborn in whom a photosensitivity eruption developed during phototherapy for treatment of hyperbilirubinemia. Free erythrocyte protoporphyrin and zinc protoporphyrin levels were markedly elevated during the neonatal period. Porphyrin levels were normal at 19 weeks of age. The infant had residual skin atrophy and showed clinical and radiologic evidence of kernicterus. The pathogenesis of transient porphyrinemia associated with hemolytic disease of the newborn is unclear.

The role of autologous blood transfusion in adolescents undergoing spinal surgery.

STUDY DESIGN: A prospective study of 147 consecutive patients undergoing spinal surgery who were analyzed for response to an effect of an offered autologous blood program. OBJECTIVES: Analysis of the impact of the autologous program within a comprehensive blood conservation philosophy toward the reduction in the use of homologous blood. METHODS: Each patient was prescreened by the autologous program for inclusions and ability. Physical parameters were recorded as were predonation and postdonation hemoglobin levels. The volume of each donation and the number of autologous and homologous units transfused and total operating blood loss were recorded as were complications during donation and transfusion. RESULTS: One hundred sixteen of the original one hundred forty-seven patients participated in the program and donated between 150 and 1900 ml of blood during the preoperative period. Of these, 35 patients weighed 45 kg or less. Diagnoses included 97 cases of idiopathic scoliosis and the remainder had spinal deformities of other causes. Of the entire group, 13 patients (11%) received homologous blood transfusion, 7 of these patients had diagnoses other than idiopathic scoliosis. CONCLUSIONS: In this study of 116 patients, 89% of the spinal surgeries were successfully completed using only autologous blood. This compared favorably with a historical control group in which 60% of the patients required homologous blood transfusion. It is concluded that the use of autologous blood donation combined with other blood conservation techniques has significantly lessened the need for homologous transfusion.

Reappraisal of optimal hemoglobin standards for female blood donors in Canada.

BACKGROUND: A hemoglobin (Hb) standard of 115 g per L on the copper sulfate test has been in use by the Canadian Red Cross Society Blood Services for female blood donor predonation screening since 1989. STUDY DESIGN AND METHODS: To determine if this lowered Hb standard results in increased iron deficiency in repeat blood donors, a study was conducted to evaluate the performance of the copper sulfate test and predonation capillary and venous Hb assays in a population of female blood donors most at risk of developing iron deficiency. RESULTS: Of the 174 donors who were of childbearing age, who were not taking iron supplements, and who had made at least three blood donations per year, 45 (25.9%) were iron deficient, and 64 (36.8%) had reduced iron stores; only 65 (37.3%) had normal iron stores. This study showed that capillary blood is more likely to have a higher Hb concentration (3.2 +/- 7.8 g/L) than venous blood samples, which could affect the performance of predonation screening assays that are based on capillary blood samples at a given discriminating value. With an Hb standard of 115 g per L, both the copper sulfate and capillary Hb assays were not sensitive enough to screen for iron deficiency (sensitivity, 27% and 33%; specificity, 96% and 93%, respectively) and were comparable only to the performance of a venous Hb assay with a cutoff value of 110 g per L (sensitivity, 27%; specificity, 99%). In contrast, an Hb standard of 125 g per L in the copper sulfate test could achieve a more optimal sensitivity of 79 percent and specificity of 78 percent. CONCLUSION: This study supports the use of a higher Hb cutoff value of 125 g per L for female blood donors in the predonation fingerstick copper sulfate test.

Primary hemochromatosis in children: report of three newly diagnosed cases and review of the pediatric literature.

Hereditary hemochromatosis was diagnosed in three asymptomatic siblings following the unexpected finding of elevated serum iron concentrations. This diagnosis was confirmed by hepatic biopsy. Repeated phlebotomies resulted in a significant decline of serum iron and ferritin concentrations and a decrease of hepatic iron content. This report and a review of the literature indicate that the diagnosis of hereditary hemochromatosis must be considered more frequently in childhood. Organ dysfunction from iron overload may be minimized in children by the early commencement of regular phlebotomy.

Autologous blood transfusion for pediatric bone marrow donors.

Nine normal bone marrow donors aged 7-166 months (median 69 months) received autologous red cells which had been removed from their marrow harvest after collection. The median volume of marrow removed from the donors was 18.6 ml/kg which was equivalent to a median blood volume loss of 23.3%. Three infant donors were transfused with autologous red blood cells intraoperatively. These cells had been salvaged from the initial marrow aliquot and were transfused while bone marrow harvesting continued. No donors required homologous blood transfusion. This technique is useful for marrow donors in the pediatric age group when preharvest autologous blood collection is not feasible or available.