Jasmina Ahluwalia

Early indicators of prognosis in fulminant hepatic failure: An assessment of the Model for End‐Stage Liver Disease (MELD) and King's College Hospital Criteria

While Kings Hospital Criteria (KCH) criteria are used worldwide, the Model for End‐Stage Liver Disease (MELD) is a more recently developed scoring system that has been validated as an independent predictor of patient survival in conditions for liver transplantation (LT). The aim of the present study was to compare MELD and KCH criteria with other early clinical prognostic indicators (CPI) in a cohort of patients with fulminant hepatic failure (FHF). A total of 144 patients (mean age 31.7 ± 14.7 yr; range 12–82 yr; 62 males) with FHF due to acute viral hepatitis were included into the study. Variables found significant on univariate analysis were entered into a multivariate logistic regression analysis. A total of 52 (36.1%) patients survived, the remaining 92 (63.9%) died. Univariate analysis showed that age, duration of jaundice, jaundice‐encephalopathy interval (JEI), grade of encephalopathy, presence of cerebral edema, bilirubin, prothrombin time, creatinine, and MELD score were significantly different between survivors and nonsurvivors. Multivariate logistic regression identified 6 independent CPI of adverse outcome on admission: age ≥50 yr, JEI >7 days, grade 3 or 4 encephalopathy, presence of cerebral edema, prothrombin time ≥35 seconds, and creatinine ≥1.5 mg/dL. Presence of any 3 of 6 CPI was optimum in identifying survivors and nonsurvivors. A MELD score of ≥33 was found to be best discriminant between survivors and nonsurvivors by the construction of receiver operating characteristic (ROC) curves. Any 3 CPI were superior to MELD and KCH criteria in predicting the outcome (c‐statistic [95% confidence interval]: CPI 0.802 [0.726–0.878], MELD 0.717 [0.636–0.789], and KCH criteria 0.676 (0.588–0.764); P values: CPI vs. MELD 0.045, CPI vs. KCH criteria 0.019, and MELD vs. KCH criteria 0.472). In conclusion, MELD and KCH criteria are not as useful as a combination of other early CPI in predicting adverse outcome in patients with FHF due to acute viral hepatitis. Liver Transpl, 2007.

Outcome of chronic idiopathic thrombocytopenic purpura in children

There is paucity of data on long‐term probability of remission in chronic idiopathic thrombocytopenic purpura (ITP). Aim was to study the course and factors influencing remission of chronic ITP. Chronic ITP was defined as thrombocytopenia persisting >6 months following initial diagnosis.

Prevalence of the H63D mutation of the HFE in north India: its presence does not cause iron overload in beta thalassemia trait

Abstract:  Objectives: To determine the allele frequency in the north Indian population of the two mutations in the HFE gene, the C282Y and H63D, which are responsible for causing hereditary haemochromatosis particularly in Caucasians of north European descent. We also wanted to correlate these mutations with the iron status in beta thalassemia traits. Patients and Methods: Sixty normal subjects and 215 individuals with beta thalassemia trait from north India were screened for the C282Y and H63D by polymerase chain reaction‐restriction fragment‐length polymorphism (PCR‐RFLP). We studied the iron status in these subjects and correlated the same with the HFE gene mutations. Results: On screening for the C282Y gene mutation, all individuals were detected to be of the wild‐type. The overall allele frequency of H63D was 9.09% with three individuals being homozygous for 63D. No statistically significant difference in the iron status was detected between the individuals of the wild‐type and mutant for H63D. Haplotyping of the homozygous 63D alleles revealed the pattern to be identical to the Europeans. Conclusions: Our study shows that H63D is prevalent and C282Y is rare in north Indians and the presence of 63D mutation does not increase body iron as measured by serum ferritin in beta thalassemia traits. Haplotype of H63D gene mutation is of an European haplotype, indicating a common origin.

Methylenetetrahydrofolate reductase gene polymorphisms: association with risk for pediatric acute lymphoblastic leukemia in north Indians.

Genetic polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene have been associated with the development of acute leukemias and various malignancies. We conducted a case–control study in 95 north Indian children with acute lymphoblastic leukemia (ALL) and 255 controls, to investigate the role of MTHFR C677T and A1298C polymorphisms as risk factors in the development of ALL. PCR-RFLP on genomic DNA was carried out to determine C677T and A1298C genotypes. The frequency of MTHFR C677T for the T allele was found to be 23.2% among patients and 18.2% among controls. The frequency of the C allele in MTHFR A1298C was 44.2% among cases and 48.2% in controls. Patients showed a higher frequency of heterozygosity for the MTHFR C677T polymorphism as compared to controls (40% vs 27.8%; OR = 1.73, 95% CI 1.02–2.91, p = 0.02), and the A1298C polymorphism did not show any difference in genotype frequency between cases and controls. MTHFR 677CC/1298AC genotype frequencies showed a statistically significant difference between cases and controls (OR = 0.58, 95% CI 0.34–1.01, p = 0.04). In conclusion, our study in north Indian controls and patients with pediatric ALL showed increased frequency for MTHFR C677T in the heterozygous state and no significant difference in the frequency of A1298C genotype between the two groups.

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.

Evaluation of the genetic basis of phenotypic heterogeneity in north Indian patients with thalassemia major.

Objectives: To assess the molecular basis of phenotypic heterogeneity in north Indian patients with thalassemia major (TM). Methods: To determine the clinical severity, 130 patients of TM were studied for the age of first presentation and frequency of blood transfusion. The type of beta mutations, Xmn–1Gγ polymorphism and G6PD Mediterranean mutation was characterized. Analysis of the phenotypic presentation and the genotype was performed. Results: Majority (83.8%) presented before 1 year of age (mean 8.8 months). The caste distribution showed 41.6% were Aroras and 32.3% were migrants from Pakistan. IVS1‐5(G→C) was commonest (32.7%) and the common five Indian mutations comprised of 88.4% of alleles. The mean age of presentation with IVS1‐5(G→C), Fr 8/9, (+G) 619‐bp del and IVS1‐1(G→T) homozygosity was 4.3, 6, 3.4 and 9.1 months respectively. Xmn–1Gγ status showed −/− in 66.9%, +/− in 26.1% and +/+ in 6.9% patients. Xmn–1Gγ−/− presented before 1 year of age. The mean age of presentation with +/+ was 18.3 months. Six hemizygous boys and one heterozygous girl with G6PD Mediterranean were found (prevalence 5.3%). Eight patients could be reclassified as thalassemia intermedia on follow up. Conclusions: This study showed that majority of TM in north India present before 1 year of age and homozygous 619‐bp deletion presents the earliest. The presence of Xmn‐1Gγ polymorphism delays the presentation, is associated with the IVS 1‐1 (G→T) and shows variable improvement with hydroxyurea therapy. Based on the results of genotyping, reevaluation of patients can improve the outcome in a few patients.

Anaemia and marrow fibrosis in patients with primary hyperparathyroidism before and after curative parathyroidectomy

Objective  To determine the relationship between anaemia and myelofibrosis in patients with symptomatic primary hyperparathyroidism (PHPT) and to assess the effect of curative parathyroidectomy on anaemia and marrow fibrosis.

HEMATOLOGICAL DISORDERS IN DOWN SYNDROME: Ten-Year Experience at a Tertiary Care Centre in North India

A total of 239 cases of Down syndrome (DS) were seen in the genetic clinic between 1992 and 2003, of which of 15 had hematological manifestations at presentation. These comprised 4 cases of transient myeloproliferative disorder (TMD), 3 cases of TMD/acute leukemia, 4 cases of acute leukemia (AL), 2 of dual deficiency anemia, and 1 case each of myelofibrosis and idiopathic thrombocytopenia. This study emphasizes the fact that an abnormal hemogram in a DS patient does not necessarily indicate AL/TMD, as a considerable number of the cases in this study had other hematological abnormalities. TMD can be differentiated from acute leukemia only on follow-up.

Arthritic presentation of childhood malignancy: beware of normal blood counts

Some children with malignancy (e.g. acute lymphoblastic leukemia) who initially present with musculoskeletal complaints may be misdiagnosed as having a rheumatological disorder. In the literature, importance has been given to subtle changes in blood counts, which may point toward an underlying malignancy. We report 3 children with malignancy, who had an arthritic presentation but had normal blood counts at presentation. Atypical clinical pattern, significant nocturnal pain, pain out of proportion to joint involvement and prominent systemic features in these children prompted us to do a bone marrow examination that revealed a malignancy. Pediatricians must be aware of the arthritic presentation of childhood malignancy. If the clinical features point toward a malignancy, bone marrow examination should always be performed even if the blood counts are normal.

Immune functions in splenectomized thalassaemic children

A prospective study to assess the immune functions in splenectomized thalassaemic children. Children were those registered in the Thalassemia major. There were 10 splenectomized children (Group 1), 10 nonsplenectomized children and 6 age-matched control (Group 3). All children were shown to be HIV seronegative. The mean concentrations of serum IgG and IgA were higher in Group 1 as compared to Groups 2 and 3 but the differences were not statistically significant. Nitroblue tetrazolium (NBT) dye reduction by stimulated polymorphonuclear leukocytes was normal in both study and control groups and the differences were not statistically significant. However, NBT reduction in the unstimulated state was much higher in Group 2 as compared to Groups 1 and 3. Phytohaemagglutinin induced mitogen proliferation was normal in all 3 groups. Children in Group 1 not only had a significantly higher absolute lymphocyte count but also had a lower CD4JCD8 ratio as compared to Groups 2 and 3. Splenectomy does appear to alter the immune status of thalassemic children but the exact mechanism by which this occurence is not clear.