Hepatic and Cardiac Iron-load in Children on Long-term Chelation with Deferiprone for Thalassemia Major

Objective: To evaluate the efficacy of prolonged deferiprone monotherapy in patients with ?-thalassemia major. Methods: This cross-sectional study included 40 patients (age range 9 to38 years) with thalassemia major receiving deferiprone for ?5 years. Serum ferritin, andmyocardial iron concentration (MIC) and liver iron concentration (LIC) assessed by T2*MRIwere recorded. Results: The patients were receiving deferiprone for a mean (SD) duration of12.1 (4.7) years. The median (IQR) dose of deferiprone was 85 (74.3, 95) mg/kg/day. TheMIC was normal or had a mild, moderate or severe elevation in 29 (72.5%), 3 (7.5%), 3(7.5%), and 5 (12.5%) patients. The LIC was normal or had a mild, moderate or severeelevation in 2 (5%), 4 (10%), 11 (27.5%) and 23 (57.5%) patients. Conclusions: The majorityof patients receiving deferiprone had a moderate/severe hepatic but normal cardiac iron load.Prolonged deferiprone monotherapy was suboptimal for hepatic iron load in the majority.

Haematological profile of 21 patients with hairy cell leukaemia in a tertiary care centre of north India.

Background & objectives: Hairy cell leukaemia (HCL) is a B cell neoplasm which constitutes around 2 per cent of all the lymphoid leukaemias. It has a characteristic morphology and immunophenotypic profile. It is important to distinguish HCL from other B cell lymphoproliferative disorders due to availability of different chemotherapeutic agents. This study presents clinical, haematological and immunophenotypic profile of patients with HCL seen over a period of four years in a tertiary care hospital in north India. Methods: Twenty one cases of hairy cell leukaemia were analyzed for their clinical details, haemogram, bone marrow examination and immunophenotypic findings. Results: Age of the patients ranged from 28-76 yr with male predominance. Weakness and fever were commonest presentations. Splenomegaly, hepatomegaly, lymphadenopathy were seen in decreasing order of frequency. Anaemia was noted in all 21 patients, leukopenia in 15 and thrombocytopenia in 19 cases. Fourteen patients were pancytopenic. Bone marrow examination showed typical hairy cells in all cases. Immunophenotyping showed expression of CD19, CD20, CD103, CD25 and CD11c in all cases, while positivity was seen for CD79b in 93.7 per cent, kappa light chain restriction in 60 per cent and lambda in 40 per cent cases. Notably, 20 per cent showed CD10 and 12 per cent showed CD23 expression. Interpretation & conclusions: This study reveals some unusual findings in otherwise classical disease entity, like absence of palpable spleen, presence of lymphadenopathy, normal or elevated leukocyte counts, expression of CD10, which at times could be diagnostically challenging.

Guidelines for screening, diagnosis and management of hemoglobinopathies.

The b‑thalassemias and sickle cell disorders are a major health burden in India. Diagnosis and management of these disorders both in adults and in newborns using appropriate approaches and uniform technology are important in different regions of a vast and diverse country as India. In view of a National Thalassemia Control Program to be launched soon, a need was felt for guidelines on whom to screen, cost‑effective technologies that are to be used as well as for establishing prenatal diagnosis programs in regional centers. Newborn screening for sickle cell disorders is in its infancy in India and uniform approaches need to be followed. Also, included are guidelines for monitoring and managing patients who are now growing older and need comprehensive care as well as management of complications of the disease.

Performance of Accredited Social Health Activists to Provide Home-based Newborn Care: A Situational Analysis.

Objective: To assess Accredited social health activists’ (ASHAs) ability to recognize illness in infants aged less than 2 months. Methods: Investigators observed 25 ASHAs conducting 47 visits. Results: ASHA-investigator agreement on the need to further assess infants was intermediate (kappa 0.48, P<0.001). Using IMNCI’s color codes, ASHAs misclassified 80% of infants. ASHAs did not follow home-based newborn care formats and skipped critical signs. Overall ASHA-investigator agreement on diagnosis was poor (kappa=0.23, P=0.01). Conclusion: There is a need for improved training, tools, and supportive supervision.

Pediatric patients with bicytopenia/pancytopenia: Review of etiologies and clinico-hematological profile at a tertiary center.

Background: The etiology of bicytopenia/pancytopenia varies widely in children, ranging from transient marrow viral suppression to marrow infiltration by fatal malignancy. Depending on the etiology, the clinical presentation can be with fever, pallor or infection. Knowing the exact etiology is important for specific treatment and prognostication. Aims: To evaluate the etiological and clinico-hematological profile in children with bicytopenia and pancytopenia. Materials and Methods: A review of bicytopenic and pancytopenic children referred for bone marrow examination from January 2007 to December 2008 was done. Detailed history, clinical examination and hematological parameters at presentation were recorded. Results and Conclusion: During the study period, a total of 990 children were referred for bone marrow examination for different indications. Of these, 571 (57.7%) had either pancytopenia (17.7%) or bicytopenia (40%). Commonest form of bicytopenia was anemia and thrombocytopenia seen in 77.5% cases, followed by anemia and leukopenia in 17.3% and leukopenia and thrombocytopenia in 5.5% cases. Most common etiology was acute leukemia (66.9%) in bicytopenic children and aplastic anemia (33.8%) in pancytopenic children. Children with bicytopenia had a higher incidence of underlying malignancy (69.5% vs. 26.6%), splenomegaly (60.5% vs. 37.4%), lymphadenopathy (41.8% vs. 15.1%) and circulating blasts (64.6% vs. 20.1%) and a lower incidence of bleeding manifestations (12.1% vs. 26.6%) as compared to children with pancytopenia.

Developmental profile in children with iron deficiency anemia and its changesafter therapeutic iron supplementation.

Objective. To evaluate the developmental profile of children with iron deficiency anemia (IDA) and the changes following iron supplementation. Methods. Study was conducted prospectively in a tertiary care teaching institution. Subjects were children aged 6 months to 5-years, with IDA, proven by hematological parameters and iron studies. Complete blood counts and iron studies were performed at the beginning and following 3-months therapy with iron. Simultaneously, development was assessed by Developmental profile II (DPII), which was interpreted using IQ equivalent (IQE) scores and ‘fractional months differential’ (FMD). Results. Thirty five children fulfilled predetermined inclusion criteria. The mean-age was 22.3±13.4 months. Majority (71.4%) had moderate, while 5 (14.3%), each had mild and severe anemia. Significant developmental delay was observed in iron deficient children. Maximum delay was observed in academic and communication domains. 6 (17.2%) failed developmental screening, with IQE scores of <70. Significant improvement in DPII scores was noticed following therapy. Although some gain in IQE scores was noticed in the majority (88.6%), significant improvement (e =>10-point gain) was observed in about half (51.4%). Interpretation of DPII by FMD revealed significant improvement in all the domains as well. Conclusion. Children with IDA have suboptimal developmental scores. The delayed development is variably reversible following oral iron therapy. Hb =<7 g/dl and age >24 months predict suboptimal outcome. FMD is a useful method of interpreting DPII.

Seckel syndrome with chromosomal 18 deletion.

Four case records of patients with Seckel Syndrome (SS) were retrieved. Typical of bird headed dwarfism was seen in all. Chromosome 18 deletion was seen in one child with SS. MRI abnormalities were detected in 3 patients. Cytogenetic studies and neuroimaging is likely to provide important diagnostic and prognostic information.

Pediatric disorders of sex development.

The management of disorders of sexual differentiation (DSD) involves a multidisciplinary approach. The main aim of analysis was to study the phenotype-karyotype correlation in North Indian children with DSD. The records of pediatric DSD were retrieved and characteristics noted. Of total of 58 children, 43 (74.1%) and 10 (17.2%) were raised as males and females respectively. The mean age at presentation was 31.3±9 months. The karyotype was 46XY in 45 (77.6%) and 46XX in 12 (20.7%). CAH was commonest cause of DSD (36.2%), followed by gonadal dysgenesis. Of the 15 patients of 46 XY CAH, there were 5 with 17-α hydroxylase deficiency, 2 with 3-β HSD deficiency and one case of lipoid adrenal hyperplasia. There was an excess of genetic males, possibly due to prevalent socio-cultural factors and gender bias favoring males. There is a need to improve the diagnostic facilities and incorporate a team approach in management of DSD.

Acute leukemia/myelodysplastic syndrome as a sequelae of carcinoma breast: a report of five cases from north India.

A second malignant neoplasm has been found to be more frequent than might be expected from the general population rates. Therapy-related myelodysplastic syndrome and acute leukemia are dreaded long-term complications of five cases of hematological malignancies following treatment for successful breast cancer therapy (therapeutic drugs or radiotherapy). We encountered carcinoma from north India over a 7-year period from 1999 to 2005. The patients presented 2-5 years after treatment of breast carcinoma. Three patients underwent surgery and received chemoradiotherapy. One patient received chemotherapy after surgery. One patient underwent only surgery and after 3 years presented with acute myeloid leukemia and bone marrow metastasis of carcinoma of the breast. At the time of presentation, all the patients had either bicytopenia or pancytopenia. A close follow-up with complete blood cell counts of the patients who previously had carcinoma of the breast is suggested for early detection of hematological abnormalities. However, the poor prognosis, limited financial resources and poor health insurance coverage results in few patients and their family members opting for treatment.

Abnormal chromatin clumping in leucocytes of Ph positive chronic myeloid leukemia cases - extending the morphological spectrum.

The syndrome of abnormal chromatin clumping is largely a morphological entity characterized by exaggerated chromatin clumping seen in the neutrophils. According to the recent World Health Organization (WHO) classification, it is categorized as a variant of atypical chronic myeloid leukemia (aCML) or Ph-negative CML. Most of the cases reported in literature have been negative for the Ph chromosome or the BCR-ABL gene. Till date, Ph positivity has been demonstrated in just one case. We report two more Ph-positive CML cases with abnormal chromatin clumping in neutrophils. To the best of our knowledge, this is only the second time in literature that such cases have been described. These two unusual cases go on to extend the morphological spectrum of granulocytic changes seen in Ph-positive CML.

Serum transferrin receptor-ferritin index shows concomitant iron deficiency anemia and anemia of chronic disease is common in patients with rheumatoid arthritis in north India.

Anemia is a frequent cause of morbidity in patients with rheumatoid arthritis (RA). We studied the prevalence of anemia of chronic disorders (ACD) and ACD with coexistent iron deficiency anemia (IDA) in patients with RA using sTfR/log ferritin ratio (sTfR - F index). Complete blood counts, percent transferrin saturation, serum ferritin, sTfR, sTfR-F index measurements were carried out in 100 anemic RA patients. Twenty-five IDA subjects without any other illness and 25 age- and sex-matched normal controls were studied. Prevalence of anemia in RA patients was 50.5%. Patients with sTfR-F index value < 1.5 were classified as pure ACD and patients with sTfR-F index value> 1.5 were classified as ACD with coexistent IDA. Using these criteria, 20% patients were found to have pure ACD and 80% patients had coexistent ACD and IDA. In the normal control group, sTfR-F index was found to be 0.16-1.8. We found that sTfR-F index can clearly distinguish IDA control cases and normal subjects with no overlap in the range of sTfR-F index.

Role of FAB classification of acute leukemias in era of immunophenotyping.

French-American-British classification for leukemias had been widely accepted due to its objectiveness and good reproducibility. WHO classification of leukemias was formulated in 1997 with a purpose of further enhancing the objectivity. However, the requirement of cytogenetics and immunophenotyping makes it difficult for many countries like India to put WHO classification in routine use. This study was carried to know the effectiveness of FAB classification in an era of technical advancement. A retrospective analysis of all acute leukemias over a period of 2 years was done. Out of total of 469 cases of acute leukemias, 193 were diagnosed as Acute Lymphoblastic Leukemia (ALL), 200 as Acute Myeloid Leukemia (AML), and 76 cases diagnosed as Acute Leukemia, cytochemically undifferentiated. Hence, only 16% of all leukemias remained unclassifiable. Subclassification of AML cases revealed a much higher percentage of AML-M3, as compared to western literature. In conclusion, FAB classification, based on morphology and simple cytochemical stains, remains effective enough, although cytogenetics and immunophenotyping can add to diagnostic accuracy in some cases.

Unconjugated hyperbilirubinemia in nonalcoholic steatohepatitis--is it Gilbert's syndrome?

BACKGROUND: Patients with nonalcoholic steatohepatitis (NASH) have normal liver function tests except for raised transaminases until they have progressed to cirrhosis of liver. The objective of this study was to evaluate patients of NASH for the presence of hyperbilirubinemia at presentation. METHOD: Sixty-seven patients of NASH were studied for the presence of hyperbilirubinemia at presentation. All patients were worked up for the presence of cirrhosis and hemolytic work up and fasting test were done in those found with unconjugated hyperbilirubinemia. RESULTS: Five out of 67 patients (7.5%) of NASH were found to have unconjugated hyperbilirubinemia. Though the fasting test was not positive, they all had a negative hemolytic workup and none of them had underlying cirrhosis. Clinical characteristics of patients with unconjugated hyperbilirubinemia were similar to those with normal serum bilirubin levels. CONCLUSION: Unconjugated hyperbilirubinemia in patients with NASH may suggest an associated Gilbert's syndrome.

Circulating D-dimers as a marker of disease activity in pulmonary sarcoidosis.

BACKGROUND AND AIMS: The search is on to find an easily measurable marker of disease activity in sarcoidosis. The present study was carried out to evaluate the utility of plasma D-dimer as a marker of disease activity in sarcoidosis. METHODS: Thirty newly diagnosed cases of sarcoidosis with clinical indications for treatment and an equal number of matched healthy controls were studied for the presence of D-dimers (DD) in the plasma before starting treatment with oral prednisolone and after clinical remission. Semi-quantitative estimations of DD were done using the latex agglutination slide test method (Commercial Kit - Diagnostica Stago, France) as per the manufacturer's recommendations. RESULTS: The mean age of cases and controls were 45.43 +/- 8.5 (range 34-60) and 46.16 +/- 8.07 (range 32-61) years, respectively. Of the 30 patients, nine (30%) were DD positive at baseline. The DD positive patients presented more often with dyspnoea, had radiological stage III (7 out of 9) disease and abnormal spirometry compared to patients with no detectable DD in their plasma. Of the 16 patients re-evaluated after clinical remission, eight (50%) were D-dimer positive. Two of the five patients initially DD positive had become negative and five additional patients who were negative at baseline had become positive. CONCLUSIONS: Plasma D-dimers, which were positive in 30% of untreated patients of sarcoidosis, indicate patients with significant pulmonary parenchymal involvement; but have no correlation with clinical disease remission.