Mamta Manglani

Guidelines for screening, diagnosis and management of hemoglobinopathies

The β-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.

Molecular characterization of leukocyte adhesion deficiency-I in Indian patients: Identification of 9 novel mutations

PURPOSE Leukocyte adhesion deficiency type-I (LAD-I) is caused by mutations in the ITGB2 gene, encoding the β2-subunit of β2-integrin (CD18) which leads to markedly reduced expression of CD18 on leukocytes resulting into recurrent life threatening infections. Here we aim to identify the molecular defects underlying LAD-I in Indian patients and correlate with the clinical presentation. METHODS Blood was collected from 30 patients and their parents for absolute neutrophil count, expression of CD18 and CD11 by flow cytometry and DNA extraction. PCR and DNA sequencing of the ITGB2 gene was done for mutation characterization. RESULTS Phenotypically, 22 patients were LAD-I(0), 1 was LAD-I(-) and 7 were LAD-I(+) showing no expression and reduced expression of CD18 respectively. Nine novel mutations in 15 patients and 11 known mutations in 16 patients were detected. Prenatal diagnosis was performed for 5 families. CONCLUSION In this study 30 patients were phenotypically and genotypically evaluated for a less known disease LAD-I. Unavailability of curative options to majority of the patients and high cost of supportive care emphasize the need to increase awareness about a suspicious case so that timely management can be given to the patient and prenatal diagnosis can be offered to their families.

A comparative clinical study to assess safety and reactogenicity of a DTwP-HepB+Hib vaccine

Hepatitis B and Haemophilus influenzae type b (Hib) infections are major public health problems in developing countries, including India. Hence, combination vaccines containing DTwP, recombinant hepatitis B and Hib conjugate vaccines have been developed. Here, we report a Phase IV study which assessed safety and reactogenicity of a new DTwP-HepB+Hib vaccine. Three doses of DTwP-HepB+Hib vaccine (Pentavac, Serum Institute of India Ltd) or Tritanrix-HB+Hib (GlaxoSmithKline Beecham) were administered to infants at 6, 10 and 14 weeks of age in 2:1 ratio. The subjects were followed till one month after the third dose for safety assessment. Adverse events were captured in structured diaries and physical examinations were performed on each visit. The study was conducted in 1510 infants. Both vaccines caused injection site local and systemic reactions and the incidence was similar in both the groups. The incidence of local solicited reactions was: tenderness 35.9 %–33.6 %; redness 18.1 %–17.2 %; swelling 23.7 %–22.4 %; induration 12.8 % –13.7 %. The percentage of systemic solicited reactions were: diarrhea 2.2 %–2.2 %; drowsiness 3.3 %–3.4 %; fever 14.0 %–11.2 %; irritability 28.1 %–25.4 %; loss of appetite 6.6 %–5.6 %; persistent crying 17.7 %–15.7 %; vomiting 3.5 %–3.0 %. No serious adverse event was caused by the vaccines. The new DTwP-HepB+Hib combination vaccine showed similar safety profile to that of an imported vaccine in Indian infants.

Rational use of blood components - an audit.

ObjectivesThe present study was designed to study appropriateness of use of the blood components in pediatric and neonatal wards.DesignIt was an observational study conducted in a tertiary care institute. The patients were selected from various pediatric subsections over a period of six months.Materials and methodsAll the patients below 12 years of age, who received blood components in any of the pediatric subsections including general pediatric wards, pediatric intensive care unit, pediatric hematology section, neonatal intensive care unit and pediatric surgery ward were included in the study. Each transfusion episode was assessed to decide whether it satisfied the predetermined criteria.ResultsOf the total 184 episodes of blood component transfusions, 153 (83.1%) episodes were appropriate and 31 (16.9%) episodes were inappropriate. Among these, fresh frozen plasma transfusions had highest inappropriate [18/41 (58%)] episodes followed by packed red cell transfusions [11/110 (35.5%)] and platelet transfusions [2/5 (6.45%)]. There was no inappropriate episode of cryoprecipitate transfusion.ConclusionsThe present study reinforces the importance of blood audit in the clinical setting. Judicious implementation of guidelines for use of various blood products may help decrease the inappropriate use of blood components.

Immunoglobulin levels and CD4 / CD8 counts in β — Thalassemia major

ObjectiveThis cross-sectional study determined the CD4, CD8 counts and serum immunoglobulins in transfusion dependent β-thalassemic patients, and correlated them with anti-HIV, anti-HCV and HBsAg status, number of transfusions, iron overload and splenectomy.MethodsPatients with acute or chronic diseases (except HIV, Hepatitis B and C), on immunosuppressive drugs or vaccinated within one month prior to study were excluded. CD4, CD8 counts and serum Immunoglobulins were documented.ResultsIncreasing transfusions led to higher IgA and IgM as well as a decline in CD4 and CD8 levels. Higher ferritin correlated with high IgM. CD4, CD8 and IgA were significantly higher in splenectomized subjects. HCV correlated significantly with lower IgA values.ConclusionHigher transfusion requirement, iron overload, splenectomy and HCV infection correlated with alterations in different immunological parameters.

HLA-B*5701 Allele in HIV-infected Indian Children and its Association with Abacavir Hypersensitivity

ObjectiveTo determine the prevalence of HLA-B*5701 allele in HIV-infected children, and to find its association with Abacavir hypersensitivity.MethodsChildren (2 to 18 y) already on, or to be initiated on Abacavir were included for PCR sequencing to detect HLA-B*5701. Outcome measures were: proportion with HLA B*5701 allele and hypersensitivity with Abacavir. Abacavir was stopped if patient tested positive for HLA-B*5701 allele.Results100 children (median age 11 y) were enrolled; 10 were already on Abacavir. HLA-B*5701 positivity was observed in 11 (11%) children. Two of these 11 children developed hypersensitivity after initiation of Abacavir. Abacavir was thereafter stopped in all who tested HLA-B*5701 positive, irrespective of the development of hypersensitivity reaction.ConclusionsHLA-B*5701 allele was present in 11 (11%) of HIV-infected children, of which two developed Abacavir hypersensitivity. None of the patients without the allele developed hypersensitivity.

Acquired methemoglobinemia–A sporadic Holi disaster

ObjectiveTo study clinical profile and outcome in patients with methemoglobinemia following exposure to toxic colors during Holi festival.MethodsThis retrospective study included 112 children (5 to 12 years) admitted with methemoglobinemia after playing Holi. Clinical and treatment details were reviewed.ResultsThe common symptoms were giddiness, vomiting and headache. Treatment included thorough skin wash, intravenous fluid and methylene blue in 111 children. Age 7-9 and > 11 years, vomiting, giddiness, cyanosis, PaO2 < 80 mm Hg and oxygen saturation < 95% were associated with higher need for methylene blue. All children had a good outcome.ConclusionTimely diagnosis and management of acquired methemoglobinemia can save lives.

Isolated conjunctival mass presenting as acute myeloid leukemia in an infant.

Ophthalmic manifestations of acute leukemia are commonly seen in the choroid and retina; however, conjunctival leukemic lesions are uncommon. We report a case of a 7-month-old female child presented with a fleshy conjunctival mass seen growing in the left eye since 1-month [Figure 1A]. The mass was deep pink in colour, painless and the conjunctiva appeared chemotic [Figure 1B]. There was no proptosis and ophthalmic examination was otherwise normal. The mass was soft-to-firm in consistency and showed prominent corkscrew vessels. A computed tomography scan showed an ill-defined, isodense mass [Figure 2] in the anterior orbit infiltrating the left medial rectus muscle (yellow arrow). An incisional biopsy was planned to ascertain the diagnosis. However, during the preoperative work-up, deranged blood counts prompted a peripheral blood smear to be performed, which showed the presence of blast cells in a background of hypochromic microcytic anaemia. A bone marrow aspirate confirmed the diagnosis of acute myeloid leukemia. The child was initiated on chemotherapy but succumbed to sepsis within 2 months of treatment.