There are several questions pertaining to dosage, duration and potential long-term toxicity of hydroxyurea (HU) therapy. Use of HU is extremely limited in eastern India because of its high cost and apprehension of its toxicities. We undertook this study to assess the clinical, biochemical and hematological efficacy of minimal dose HU (10 mg/kg/day) in 118 sickle cell anemia patients (27 pediatric and 91 adults). The frequency of painful crises reduced significantly in 71.5 and 92.2% in pediatric and adult cases, respectively. Ninety-five percent of the patients became transfusion independent. The baseline Hb F, total hemoglobin (Hb), MCV, MCH and MCHC levels increased significantly, whereas the WBC, platelet count and total serum bilirubin values decreased significantly. This is the first study of minimal dose HU therapy in eastern India that showed impressive improvement in clinical and hematological parameters with minimal toxicity.

This study describes the use of hydroxyurea therapy in patients with HbSD-Punjab. Low dose hydroxyurea (10 mg/kg/day) was found to be effective in reducing the clinical severity in patients with HbSD-Punjab without any short-term toxicity. In view of easy affordability amongst poor patients, widespread acceptability by patients and doctors, the need of infrequent monitoring and its potential effectiveness, low dose hydroxyurea is suitable for treatment of patients with HbSD-Punjab.

Hematopoietic stem cell transplantation (HSCT) is the only cure for thalassemia major (TM), which inflicts a significant 1-time cost. Hence, it is important to explore the cost effectiveness of HSCT versus lifelong regular transfusion-chelation (TC) therapy. This study was undertaken to estimate incremental cost per quality-adjusted life-year (QALY) gained with the intervention group HSCT, and the comparator group TC, in TM patients. A combination of decision tree and Markov model was used for analysis. A hospital database, supplemented with a review of published literature, was used to derive input parameters for the model. A lifetime study horizon was used and future costs and consequences were discounted at 3%. Results are presented using societal perspective. Incremental cost per QALY gained with use of HSCT as compared with TC was 64,096 (US$986) in case of matched related donor (MRD) and 1,67,657 (US$2579) in case of a matched unrelated donor transplantation. The probability of MRD transplant to be cost effective at the willingness to pay threshold of Indian per capita gross domestic product is 94%. HSCT is a long-term value for money intervention that is highly cost effective and its long-term clinical and economic benefits outweigh those of TC.

Hb D-Punjab [β121(GH4)Glu→Gln] is prevalent in the northern states of the Indian subcontinent. Due to inadequate data from Asian countries, the origin and spread of the Hb D-Punjab mutation are uncertain. In a study of sickle cell hemoglobinopathies, we detected the Hb D-Punjab mutation in 25 subjects from 11 unrelated Agharia families. Twelve cases were Hb S [β6(A3)Glu→Val]/Hb D-Punjab compound heterozygotes and 13 were Hb D trait carriers. In 76.0% of the cases, the β(D) gene was linked to haplotype I, whereas 24.0% had a novel haplotype. None of the haplotypes matched the β(A) haplotype of the local population. In view of the ancestral origin of the subjects and the high prevalence of the β(D) gene in the states of northern India, we suggest a North Indian origin for the β(D) mutation in our population. The finding of a novel haplotype in eastern India supports the hypothesis of a multicentric origin of this mutation.

Hb D-Punjab (HBB: c.364G>C) is an abnormal hemoglobin (Hb) associated with genetic risk in association with Hb S (HBB: c.20A>T). In addition, misdiagnosing homozygosis for hemizygosis may have implication for genetic risk assessment. We present the diagnostic utility of high performance liquid chromatography (HPLC) in differential diagnosis between the Hb D-Punjab homozygote and the Hb D-Punjab/β-thalassemia (β-thal) genotype. The Hb A2 level measurement may not be a reliable parameter to differentiate between the two conditions. In a screening program for risk prediction, the genotype should be confirmed by family study and/or molecular analysis. Misdiagnosis can have potentially adverse implications in a prenatal diagnosis (PND) program, particularly in areas where consanguinity is common and this Hb D-Punjab variant occurs.

HbS-Hofu has a variable clinical presentation. The retention time of Hb Hofu on HPLC is very close to that of HbA(0) and often elutes in the A0 window. Thus, there is every possibility of the HbS-Hofu chromatogram to be misinterpreted as that of a sickle cell trait/transfused sickle cell-beta-thalassemia case. This is the first time where Hb Hofu has been detected by HPLC, which is the widely accepted screening technique for hemoglobinopathies around the world.

HbF reduced the frequency of VOC but had no influence on the hemolytic markers in HbSD. HbSD with alpha thalassemia was associated with hypohromic and microcytic features of red blood cells.

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