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Vaso-occlusive crisis (VOC) occurs more frequently during stress in sickle cell disease patients. Epinephrine released during stress increases adhesion of sickled red blood cells (RBCs) to endothelium and to leukocytes, a process mediated through erythrocyte cyclic adenosine monophosphate (cAMP). Increased adhesion of sickled RBCs retards blood flow through the capillaries and promotes vaso-occlusion. Therefore, we examined the association of RBC-cAMP levels with frequency of acute pain episodes in sickle cell disease subjects. Using a case control study design, we measured RBC-cAMP levels, fetal hemoglobin (Hb F), α-thalassemia (α-thal) and other hematological parameters at baseline (sham treated) and after stimulation with epinephrine. The cases consisted of sickle cell disease subjects with three or more acute pain episodes in the last 12 months, and those without a single acute pain episode in the last 12 months were considered as controls. Significantly higher cAMP values were found in cases than the controls, in both sham treated (

We report four cases of compound heterozygotes for Hb S (HBB: c.20A>T) and a rare β0-thalassemia (β0-thal) mutation, Hb Westdale (HBB: c.380_396delTGCAGGCTGCCTATCAG), characterized by a 17 bp delet...

Sickle cell anemia is hallmarked by hemolysis, which releases hemoglobin (Hb) into the plasma promoting vaso-occlusive crisis (VOC). Haptoglobin (Hp) clears free Hb and decreases Hb-related pathophysiology in sickle cell anemia. There are two alleles (HP1 and HP2) and three genotypes (HP1-1, HP1-2 and HP2-2) of Hp with different frequencies in different populations. This study involved Hp level and genotype among normal and sickle cell anemia patients with varying severity of VOC. A total of 297 sickle cell anemia patients and 98 healthy controls were selected for the study. The sickle cell anemia patients were categorized as 'mild-phenotype' with no pain episodes and 'severe-phenotype' as having three or more acute pain episodes in the preceding 12 months. The Hp level was significantly lower (

During pregnancy, the iron requirement increases to meet the optimal growth of the fetus and prevent iron deficiency anemia-related complications in the mother. However, in sickle cell disease (SCD) primarily due to repeated blood transfusions and hemolysis-induced recycling of iron, its supplementation during pregnancy remains questionable and may be harmful.Twenty-five pregnant women with homozygous SCD and 25 pregnant women with normal hemoglobin variants were included as cases and control, respectively. Pregnancy and sickle cell anemia (SCA) were diagnosed using standard protocols. The serum iron, serum ferritin, total iron-binding capacity (TIBC), percentage transferrin saturation and C-reactive protein were estimated, as per the manufacturer's protocol. The complete blood count was performed. The unpaired 't-test' was performed using the SPSS v23.0 and the principal component analysis (PCA) was performed using the online software MetaboAnalyst for statistical analysis.The studied cases had significantly lower mean hemoglobin and higher mean corpuscular volume (MCV), compared to controls. The mean serum-iron, serum-ferritin and percentage transferrin-saturation in the cases were significantly higher than that of the controls, while the TIBC was lower in the cases (p0.0001). The mean level of serum iron, ferritin, percentage transferrin saturation and TIBC were 309.44 ± 122.40mcg/dl, 860.36 ± 624.64ng/ml, 42.6 ± 17.30% and 241.32 ± 96.30 mcg/dl, respectively, in the cases and 95.36 ± 41.90mcg/dl, 122.28 ± 49.70ng/ml, 15.83 ± 3.10% and 492.6 ± 149.40mcg/dl in the controls, respectively. Higher MCV, mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC) with lower hemoglobin (Hb) were noted in the cases. The PCA revealed that the cases were more heterogeneous in terms of the variability of the iron status and hematological indices than the controls.The current study shows iron sufficiency in most cases of pregnancy with SCA and suggests that evaluation of iron status must be made before initiating iron prophylaxis in pregnant women with SCA, especially in regions having a high prevalence of sickle cell hemoglobinopathy.

Vascular complications of sickle cell anemia (SCA) are influenced by many factors. Elevated plasma homocysteine (Hcy) is supposed to be an independent risk factor and is either genetic or nutritional origin. The present study evaluated the plasma Hcy level, MTHFR C677T gene polymorphism, effect of folic acid (FA) supplementation‚ and hemato-biochemical parameters in SCA and their effect on the vaso-occlusive crisis (VOC) in SCA patients of an Asian-Indian haplotype population. One hundred twenty cases of SCA (HbSS) and 50 controls with normal hemoglobin(HbAA) were studied. It was found that the plasma Hcy level is significantly higher (p

Sickle cell disease (SCD) is a Mendelian single gene disorder with highly variable phenotypic expression. In the present study, we analyzed the influence of HbF, alpha thalassemia and other hematological indices to determine their association with acute pain episodes.This case control study consisted of SCD subjects with HbS phenotype experiencing three or more acute pain episodes in last twelve months (cases) and without any episode of acute pain during last twelve months (controls). Hematological parameters, HbF, and presence of alpha thalassemia were assessed in all subjects.A statistically significant difference between HbF levels (P 0.025, χ2 test) and alpha thalassemia (P 0.008, χ2 test) was observed between controls and cases group. Univariate analysis indicated that increased HbF levels 25% (OR: 0.37, 95% CI: 0.18-0.77, P 0.008) and presence of alpha thalassemia (OR: 0.53, 95% CI: 0.33-0.85, P 0.009) provided protection, while multivariate analysis revealed significant protection was attributable only by higher HbF levels (OR: 0.39, 95% CI: 0.17-0.88, P 0.025). Significantly higher HbF levels were observed only in the 11-20 age group of cases in comparison to controls (Student's t-test, P 0.001).Higher concentrations of HbF are associated with protection against frequent episodes of acute pain crisis in SCD patients.

We describe here a rare β-globin gene variant, Hb Tianshui [β39(C5)Glu→Arg; HBB: c.119A > G], detected during routine screening in Odisha, India. This is the second report of Hb Tianshui and the first to describe the cation exchange high performance liquid chromatography (HPLC) and DNA studies of two cases of this variant. Both cases had coinherited Hb S (HBB: c.20A > T) but none presented with typical symptoms of sickle cell disease. One of the cases was heterozygous for a common α-thalassemia (α-thal) allele (-α(3.7)) (rightward) (NG_000006.1: g.34164_37967del3804) and marginally raised Hb F percentage, while the other Hb S/Hb Tianshui case was completely benign and healthy. An atypical Asian Indian haplotype [+ - + - +] could be assigned to the Hb Tianshui variant. Hb Tianshui seems to mimic a few other Hb variants in cation exchange HPLC. However, we report two specific patterns in the chromatograms that are characteristic to Hb Tianshui. Combining an alkaline electrophoresis result with cation exchange HPLC at screening would be preferred to detect this rare variant, especially in regions with considerable frequency of Hb E [β26(B8)Glu→Lys; HBB: c.79G > A] or Hb S.

In this short report, we describe the clinical presentation of a rare hemoglobin (Hb) variant, Hb Limassol [β8(A5)Lys→Asn; HBB: c.27G>C] with a faster electrophoretic mobility than Hb A and that elutes in the P3 window on cation exchange high performance liquid chromatography (HPLC). This sequence variation at codon 8 (AAG>AAC) of the HBB gene was found in the four heterozygous cases, all of whom were clinically asymptomatic.

Many host genetic factors are associated with the disease severity and fatal outcome of falciparum malaria. CD40L gene has been found to be one of the most important factors associated with malaria in African countries. This study was aimed to investigate the possible association of CD40L gene polymorphism in severe falciparum malaria in Indian adults.One hundred fifteen adult cases with severe falciparum malaria were included in the study. Two single- nucleotide polymorphisms (SNPs) of CD40L gene, CD40L-726(C/T) and CD40L+220(C/T) were investigated, and the possible association with different clinical sub-phenotypes of severe falciparum malaria were analyzed.Statistically no significant difference was observed in the incidence of CD40L-726C between the patients and control group. The incidence of CD40L+220C allele was found to be significantly higher (OR, 2.25; p = 0.03) in male patients compared to controls but no significant difference was observed in females. Haplotype data showed the susceptibility of -726T/+220C haplotype to severe malaria whereas -726C/+220T was associated with protection against severe malaria. CD40L+220C allele was associated with severe malarial anaemia in males (χ2 = 6.60; p = 0.01).CD40L gene polymorphism was found to be associated with severe falciparum malaria in Indian population especially in severe malarial anaemia. CD40L may be considered as a factor of immunity in understanding the pathophysiology of falciparum malaria.

Background Despite compelling evidence that hydroxyurea is safe and effective in sickle cell disease, it is prescribed sparingly due to several barriers like knowledge gaps in certain genotypes, apprehension about its safety and toxicity, and limited resources. We undertook this study to find out the efficacy and safety of HU in patients with HbSβ+-thalassemia with IVS1–5(GC) mutation. Procedure We registered 318 patients with HbSβ+-thalassemia with IVS1–5(GC) mutation. Of these, 203 were enrolled for hydroxyurea treatment at a low and fixed dose of 10 mg/kg/day. One hundred four patients (Group-I: 37 children and Group-II: 67 adults) with ≥2 years of hydroxyurea treatment were studied. Results The rate of vaso-occlusive crises, requirement of blood transfusion and rate of hospitalization reduced from 3 to 0.5, 1 to 0 and 1 to 0 in Group-I and 3 to 0, 1 to 0 and 0.5 to 0 in Group-II respectively after HU therapy (P

Background Although hydroxyurea is the only effective agent for the treatment of sickle cell disease, published experience with this drug is limited to treatment of homozygous sickle cell anemia and HbS/β thalassemia. The role of hydroxyurea in the treatment of patients with HbSD-Punjab, a rare hemoglobinopathy with phenotypic expression similar to that of sickle cell anemia is unknown. Procedure Over a period of 10 years, we followed 42 patients with HbSD-Punjab, of which 20 presented with severe clinical manifestations (≥3 episodes of VOC and/or ≥2 units of blood transfusion in the previous 12 months). These 20 patients were enrolled for treatment with hydroxyurea at a dose of 10 mg/kg/day and followed prospectively for a period of 24 months. Results The frequency of VOC decreased significantly and none of them required blood transfusion while receiving hydroxyurea. The HbF, total hemoglobin, MCV, MCH, and MCHC levels increased significantly, whereas HbS, WBC, platelet count, total serum bilirubin, and LDH levels decreased significantly in all the patients. No short-term drug toxicity was observed. Conclusion 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. Pediatr Blood Cancer 2014; 61:1341–1346. © 2014 Wiley Periodicals, Inc.

Exposure to sunlight can trigger various biological responses ranging from sun-burn, erythema to skin cancer. Synthetic sunscreen formulations available in market pose variety of adverse effects. Therefore formulation of the herbal sunscreen formulation and evaluation of its sun protection activity is an important aspect in the cosmetic industry. The various herbal agents contain significant sun screen properties which might be useful for formulating herbal creams and lotions. Therefore evaluation of its sun protection activity is an important aspect in the cosmetic industry. The comparative values of the calculated sun protection factor of twelve commonly used vegetables were evaluated using Mansur equation. Hydroalcoholic herbal extracts were obtained and absorbances were recorded between 290-320 nm using UV-Vis spectrophotometer. It was observed that all of the tested herbal extracts showed some UV protection capabilities with hydroalcoholic extract. Hydroalcoholic extract of beet root showed highest SPF i.e. 39.48 while capsicum extract showed lowest i.e. 2.45. These plant herbals can be formulated in the form of cosmetics formulation because of their better acceptability, less irritant nature and also these are less expensive.

Hereditary persistence of foetal haemoglobin (HPFH) is a rare inherited haemoglobin disorders in India. We encountered five cases of HPFH-3 in heterozygous condition in a single family of western Odisha, India. All the cases had raised % HbF (26.1±3.23%) with pancellular distribution of HbF in erythrocytes. There were no abnormalities found in the red cell indices. All the cases were asymptomatic till date with normal growth and development. Molecular confirmation of this haemoglobin disorders is important for control and prevention of haemoglobinopathies in this region.

Despite compelling evidence that hydroxyurea is safe and effective in sickle cell disease, it is prescribed sparingly due to several barriers like knowledge gaps in certain genotypes, apprehension about its safety and toxicity, and limited resources. We undertook this study to find out the efficacy and safety of HU in patients with HbSβ(+) -thalassemia with IVS1-5(G→C) mutation.We registered 318 patients with HbSβ(+) -thalassemia with IVS1-5(G→C) mutation. Of these, 203 were enrolled for hydroxyurea treatment at a low and fixed dose of 10 mg/kg/day. One hundred four patients (Group-I: 37 children and Group-II: 67 adults) with ≥2 years of hydroxyurea treatment were studied.The rate of vaso-occlusive crises, requirement of blood transfusion and rate of hospitalization reduced from 3 to 0.5, 1 to 0 and 1 to 0 in Group-I and 3 to 0, 1 to 0 and 0.5 to 0 in Group-II respectively after HU therapy (P 0.0001). %HbF level, hemoglobin, MCV and MCH increased significantly, whereas HbS, WBC, platelet count, serum-bilirubin and LDH levels decreased significantly after HU therapy. It has been observed that along with fairly subtle hematological changes following HU therapy, there was a substantial clinical improvement occurred in these patients. Transient myelotoxicity was observed in 4.8%. There was minimal gonadal toxicity without affecting reproductive function.In view of easy affordability, better acceptability, minimal toxicity, the need of infrequent monitoring and its potential effectiveness, low and fixed dose of hydroxyurea is suitable for treatment of patients with HbSβ(+) -thalassemia in resource poor setting.

Although hydroxyurea is the only effective agent for the treatment of sickle cell disease, published experience with this drug is limited to treatment of homozygous sickle cell anemia and HbS/β thalassemia. The role of hydroxyurea in the treatment of patients with HbSD-Punjab, a rare hemoglobinopathy with phenotypic expression similar to that of sickle cell anemia is unknown.Over a period of 10 years, we followed 42 patients with HbSD-Punjab, of which 20 presented with severe clinical manifestations (≥3 episodes of VOC and/or ≥2 units of blood transfusion in the previous 12 months). These 20 patients were enrolled for treatment with hydroxyurea at a dose of 10 mg/kg/day and followed prospectively for a period of 24 months.The frequency of VOC decreased significantly and none of them required blood transfusion while receiving hydroxyurea. The HbF, total hemoglobin, MCV, MCH, and MCHC levels increased significantly, whereas HbS, WBC, platelet count, total serum bilirubin, and LDH levels decreased significantly in all the patients. No short-term drug toxicity was observed.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.

Summary Introduction HbSD-Punjab (HbSD) is a less common form of sickle cell disease (SCD) and discrimination between HbSD and HbSS is not possible on alkaline electrophoresis because the two variants overlap in the compound heterozygous state. There are only a few publications consisting mostly of case reports. Thus, the phenotypic expression of HbSD and its modifiers has not been studied. Methods We studied the phenotypic expression of 42 cases of HbSD (the largest number of subjects ever included in this kind of study) and compared them with 84 HbSS cases matched for age, sex, and caste. Further, we evaluated the influence of HbF concentration and alpha thalassemia on the phenotypic expressions of HbSD, namely the frequency of VOC and degree of hemolysis. Results The frequencies of VOC were similar in both the groups. The markers of hemolysis such as total bilirubin, unconjugated bilirubin, and LDH were higher where as HbF concentration was significantly low in HbSD. There was a negative correlation between HbF concentration and risk of VOC in the HbSD. The total hemoglobin level and hematocrit were significantly high, and the MCV and MCH were significantly low in HbSD with alpha thalassemia. Alpha thalassemia had no influence on the frequency of VOC and severity of hemolysis in HbSD. Conclusion 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.

The Sindhi is one of the largest linguistic communities, migrated about 65 years back from the Sind province of West Pakistan to India. Though they share so many common practices with the Punjabis (especially those from Multan) and Gujarati Lohanas restricted endogamy and occupational specificity among this community is prominent [1]. Linguistically the community has been classified under the Indo-European linguistic sub-division and racially proximity has been postulated with the Mediterranean and Alpo-Dinarics. Earlier investigation among the Sindhis of Nagpur city has revealed the existence of a number of subgroups with marked territorial identity and these subgroups were found to be heterogeneous with respect to selected sero-genetic loci [2].

Objectives: Prevention of β-thalassaemia trait will, for the foreseeable future, hinge on effective screening strategies. Routine use of haematological data from automated cell counters may complement the results of the Naked Eye Single Tube Red cell Osmotic Fragility Test (NESTROFT), especially because of the high cost of a false-negative error. Our objective was to assess the potential additive value of routine haematological data in screening for β-thalassaemia trait. Settings: Community survey of asymptomatic volunteers. Methods: Using the NESTROFT results, haematological data and haemoglobin A2 concentration from 1435 young, asymptomatic Sindhi subjects recruited in a population-based survey, and statistical analysis by classification tree approach, we examined whether haematological parameters have discriminatory utility additional to that of NESTROFT in screening for β-thalassaemia trait. Results: We observed that in the derivation subset from which the classification tree was generated, there was only a marginal – albeit statistically significant – improvement in the screening performance of NESTROFT, whereas there was no such improvement attributable to the use of haematological parameters in a separate validation subset. Conclusion: Our results further substantiate the claim that the use of NESTROFT is highly indicated for screening for β-thalassaemia trait in regions where the prevalence is high and the resources are constrained.