Publications by authors named "Reena Das"

168 Publications

A novel ATRX splice variant causing acquired HbH disease in myelodysplastic syndrome with excess blasts-1.

Cancer Genet 2021 Jul 20. Epub 2021 Jul 20.

Department of Hematology, Postgraduate Institute of Medical Education & Research, Chandigarh, India. Electronic address:

A 60-year-old male with myelodysplastic syndrome with excess blasts-1 had unexplained microcytic hypochromic anemia. The cause of his anemia was revealed on supravital staining, hemoglobin studies and next-generation sequencing to be a novel hemizygous potentially pathogenic missense/splice site variant NM_000489.5:c.6848A>C, (p.Lys2283Thr) in exon 31 of the ATRX gene.
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http://dx.doi.org/10.1016/j.cancergen.2021.07.001DOI Listing
July 2021

CE-HPLC Derived P2 and P3-Peaks in Health and in Hb D-Punjab and HbE States.

Indian J Hematol Blood Transfus 2021 Jul 8;37(3):503-504. Epub 2020 Oct 8.

Department of Hematology, Postgraduate Institute of Medical Education and Research, Level 5, Research Block A, Sector 12, Chandigarh, 160012 India.

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http://dx.doi.org/10.1007/s12288-020-01363-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8239074PMC
July 2021

Next-Generation Sequencing Based Approach to Identify Underlying Genetic Defects of Glanzmann Thrombasthenia.

Indian J Hematol Blood Transfus 2021 Jul 24;37(3):414-421. Epub 2020 Oct 24.

Department of Hematology, Post Graduate Institute of Medical Education and Research, Chandigarh, 160012 India.

Glanzmann thrombasthenia (GT) is an autosomal recessive platelet function disorder characterized by mucocutaneous bleeding as the most common clinical phenotype. Patients with GT have normal platelet counts, platelet morphology but reduced platelet aggregation in response to various agonists. Homozygosity or compound heterozygosity for variants in the genes is the genetic basis for GT. Establishing a molecular diagnosis is definitive and is important for predictive testing. Using multi-gene panels is an accurate, faster, and cost-effective mode as compared to Sanger sequencing in large genes. We used a targeted resequencing based approach to identify pathogenic variants in eight cases in seven families. These variants were validated using Sanger sequencing in patients as well as family members and were predicted probably pathogenic using prediction tools. The variants include three missense (3/7 = 43%) (c.1028 T > C, c.1186G > A, c.1388G > C), two deletions (c.559delG, c.3092delT), one duplication (c.1424_1427dupAGGT) and nonsense variant (c.2578C > T, p.Gln860Ter). Except for one case which was compound heterozygous, the rest of the cases were homozygous. We found two novel variants that are reported for the first time in GT. The targeted resequencing based approach revealed varied genetic variants in North Indian patients, including two novels ones. The high yield of our panel indicates its suitability for usage in larger cohorts for the genetic diagnosis of GT patients. This approach is cost-effective and less cumbersome as compared to Sanger sequencing for these large size genes with multiple exons. The information so obtained is helpful in prenatal testing, carrier analysis, and genetic counseling.
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http://dx.doi.org/10.1007/s12288-020-01368-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8239080PMC
July 2021

An Autopsy Case of β-Thalassemia Major Illuminating the Pathological Spectrum of the Disease.

Hemoglobin 2021 May 30;45(3):180-185. Epub 2021 Jun 30.

Department of Pediatrics, Pediatric Hematology-Oncology Unit, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Despite declining rates worldwide, autopsy studies remain invaluable tools to expand existing knowledge on the pathophysiology of diseases, especially those with multisystem involvement. β-thalassemia major (β-TM) is a relatively common hemoglobinopathy in India and is characterized by a regular requirement for life-sustaining transfusions and chelation. The iron overload is an invariable side effect. This secondary hemosiderosis leads to several complications, primarily in the heart, liver, pancreas, and endocrine organs. Despite adequate transfusion and chelation, untransplanted patients may show early mortality for several reasons. We report a 10-year-old boy with β-TM who died with clinical possibilities of iron overload-related cardiac failure and pulmonary arterial hypertension. His autopsy revealed certain unique disease pathologies in the form of minimal cardiac fibrosis in the presence of significant cardiac siderosis and widespread endocrine damage due to iron-overload. A null-cell pituitary microadenoma, previously undescribed in thalassemia syndromes, was found. This report highlights the importance of the diminishing art of autopsy, without which these histopathological insights would not have emerged.
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http://dx.doi.org/10.1080/03630269.2021.1941080DOI Listing
May 2021

A case series highlighting structured hematological, biochemical and molecular approach to clinical oral iron refractoriness in children: A pressing need for a 3-tier system for classification of variants in TMPRSS6 gene.

Blood Cells Mol Dis 2021 07 16;89:102569. Epub 2021 Apr 16.

Pediatric Hematology-Oncology Unit, Department of Pediatrics, India. Electronic address:

In current study, we discuss clinical oral iron refractoriness cases and highlight need for a classification system to define TMPRSS6 gene variants. Out of 231 cases of microcytic hypochromic anemia screened (Sept 2019-Dec 2020), 17 cases (7.35%) with unexplained iron refractoriness (URIDA) phenotype were enrolled after ruling out secondary causes and compliance related issues. 11 (65%) had absent/negligible response (0-0.4 g/dl Hb rise) while 6 (35%) partial (0.5-0.9 g/dl Hb rise) response to initial iron trial at 4-8 weeks. Of these 17 cases, inappropriate hepcidin levels (normal-high) were noted in 11/15 (73%) tested. TSAT/Hepcidin ratio was low in 13/15 (87%). Genetic analysis of TMPRSS6 gene by NGS revealed variations in 15/17 (88%) cases. 10/15 cases with variations harbored a common splice site INDEL that was noted to be pathogenic SNP (MAF-0.19) on case-control association study in combination with other known missense SNPs with an odds ratio of 6.38 and relative risk 2.66 (p- < 0.01).
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http://dx.doi.org/10.1016/j.bcmd.2021.102569DOI Listing
July 2021

Hb Brugg [:c.63C>A]: Report of an Ultra-Rare Variant Hemoglobin and Its Co-inheritance with Hb D-Punjab.

Indian J Hematol Blood Transfus 2021 Apr 10;37(2):326-328. Epub 2020 Aug 10.

Department of Hematology, Level 5, Research Block A, Postgraduate Institute of Medical Education and Research, Sector 12, Chandigarh, India.

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http://dx.doi.org/10.1007/s12288-020-01331-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8012423PMC
April 2021

Congenital erythrocytosis.

Eur J Haematol 2021 Jul 23;107(1):29-37. Epub 2021 Apr 23.

Department of Hematology, Postgraduate Institute of Medical Education & Research, Chandigarh, India.

Erythrocytosis, or increased red cell mass, may be labeled as primary or secondary, depending on whether the molecular defect is intrinsic to the red blood cells/their precursors or extrinsic to them, the latter being typically associated with elevated erythropoietin (EPO) levels. Inherited/congenital erythrocytosis (CE) of both primary and secondary types is increasingly recognized as the cause in many patients in whom acquired, especially neoplastic causes have been excluded. During the past two decades, the underlying molecular mechanisms of CE are increasingly getting unraveled. Gain-in-function mutations in the erythropoietin receptor gene were among the first to be characterized in a disorder termed primary familial and congenital polycythemia. Another set of mutations affect the components of the oxygen-sensing pathway. Under normoxic conditions, the hypoxia-inducible factor (HIF), upon hydroxylation by the prolyl-4-hydroxylase domain protein 2 (PHD2) enzyme, is degraded by the von Hippel-Lindau protein. In hypoxic conditions, failure of prolyl hydroxylation leads to stabilization of HIF and activation of the EPO gene. CE has been found to be caused by loss-of-function mutations in VHL and PHD2/EGLN1 as well as gain-of-function mutations in HIF-2α (EPAS1), all resulting in constitutive activation of EPO signaling. Apart from these, globin gene mutations leading to formation of high oxygen affinity hemoglobins also cause CE. Rarely, bisphosphoglycerate mutate mutations, affecting the 2,3-bisphosphoglycerate levels, can increase the oxygen affinity of hemoglobin and cause CE. This narrative review examines the current mutational spectrum of CE and the distinctive pathogenetic mechanisms that give rise to this increasingly recognized condition in various parts of the world.
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http://dx.doi.org/10.1111/ejh.13632DOI Listing
July 2021

Autosomal dominant familial periodic fever patient with a missense variant c.215G>A (p.Cys72Tyr) in TNFRSF1A gene presenting as neutrophilia.

Eur J Med Genet 2021 May 19;64(5):104191. Epub 2021 Mar 19.

Department of Hematology, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India. Electronic address:

Familial periodic fever (FPF) is an uncommonly diagnosed autosomal dominant disorder caused by a genetic alteration in the TNFRSF1A gene. These patients usually present with fever which is usually under-investigated and under-diagnosed. In untreated cases, amyloidosis is a frequent complication. We present a 24 years male who had a history of fever from childhood, however, remained undiagnosed short of genetic testing. He has recurrent episodes of fever. During the episodes of fever, he was found to have leukocytosis (total leukocyte count- 25.7 x10^9/L) and neutrophilia (absolute neutrophil count- 22.7 x10^9/L) both of which came back to normal limits as the fever subsided. On further evaluation for neutrophilia, the exclusion of common causes of neutrophilia was done. Next-generation sequencing detected a missense variant in TNFRSF1A: c.215G > A (p.Cys72Tyr) which was confirmed by Sanger sequencing. This variant has been described in the literature in anecdotal cases of FPF. This is a first case report from the Indian subcontinent reporting TNFRSF1A: c.215G > A (p.Cys72Tyr) variant in a patient of FPF. Short of genetic testing, the fever would remain a diagnostic dilemma in this patient. This report highlights the importance of targeted resequencing in clinching diagnosis in such patients.
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http://dx.doi.org/10.1016/j.ejmg.2021.104191DOI Listing
May 2021

Indian Society of Hematology and Blood Transfusion (ISHBT) Consensus Document on Hematological Practice During COVID-19 Pandemic.

Indian J Hematol Blood Transfus 2021 Feb 16:1-9. Epub 2021 Feb 16.

SCB Medical College, Cuttack, India.

The SARS-CoV-2 (COVID-19) pandemic is a worldwide public health emergency with widespread impact on health care delivery. Unforeseen challenges have been noted during administration of usual haematology care in these unusual COVID-19 times. Medical services have been overstretched and frontline health workers have borne the brunt of COVID-19 pandemic. Movement restrictions during lockdown prevented large sections of population from accessing health care, blood banks from holding blood drives, and disrupted delivery of diagnostic hematology services. The disruption in hematology care due to COVID-19 pandemic in India has been disproportionately higher compared to other subspecialities as hematology practice in India remains restricted to major cities. In this review we chronicle the challenges encountered in caring for hematology patients during the COVID-19 pandemic in India and put forth recommendations for minimizing their impact on provision of hematology care with special emphasis on hematology practice in lower and middle income countries (LMICs).
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http://dx.doi.org/10.1007/s12288-021-01405-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7885311PMC
February 2021

Achondroplasia-First Report from India of a Rare FGFR3 Gene Variant.

Lab Med 2021 Sep;52(5):499-502

Genetic Metabolic Unit, Department of Pediatrics, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and Research, Chandigarh, India.

The clinical manifestations of FGFR3 sequence variations can vary from mild unnoticed short stature to neonatal lethal dwarfism and can be causative of phenotypes including achondroplasia, hypochondroplasia, and thanatophoric dysplasia. Clinical data describe an 11 month old girl with restricted growth and preserved intellect. She had rhizomelic short stature with peculiar facies but no Acanthosis nigricans. In view of the absence of the hotspot mutation c.1138 G>A/G>C (p.Gly380Arg), complete gene sequencing was done that revealed a rare sequence variation, NM_000142.4:c.1043C>G (p.Ser348Cys) in FGFR3. This sequence variation has not been reported from India so far. This report emphasizes the benefit of sequencing the whole gene in individuals who are negative for hotspot mutation of achondroplasia with strong clinical suspicion.
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http://dx.doi.org/10.1093/labmed/lmaa116DOI Listing
September 2021

The relative expression levels of CD148 and CD180 on clonal B cells and CD148/CD180 median fluorescence intensity ratios are useful in the characterization of mature B cell lymphoid neoplasms infiltrating blood and bone marrow - Results from a single centre pilot study.

Int J Lab Hematol 2021 Jan 17. Epub 2021 Jan 17.

Department of Hematology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.

Introduction: The categorization of mature B cell neoplasms (MBN) infiltrating blood and bone marrow are met with difficulties. The inclusion of CD148 and CD180 in the routine flow cytometry/FCM panels has been suggested to refine the diagnosis. We studied the discriminatory ability of CD148 and CD180 median fluorescence intensity(MFI), CD148/CD180 ratio and their expression relative to T cells (CD148 , CD180 ), neutrophils (CD148 , CD180 ) and normal B cells (CD148 , CD180 ) in the differentiation of mature B cell neoplasms (MBN) especially non-chronic lymphocytic leukaemia (CLL).

Methodology: The flow cytometric (FCM) expression of CD148 and CD180 was studied prospectively in 102 patients (non-CLL; n = 72); diagnosed by a comprehensive panel of immunophenotypic and cytogenetic studies. The MFI and ratios were statistically compared across MBNs by Mann-Whitney U test. Cut-off values, sensitivity and specificity were calculated for significant parameters by receiver operator characteristic curve.

Results: CD180MFI > 4.35 showed 100% sensitivity and 90.9% specificity for a diagnosis of marginal zone lymphoma (MZL) while, CD148/180 > 5.15 was 100% specific and 81.8% sensitive for lymphoplasmacytic lymphoma. CD148 (>4.3; 100% specificity, 83.4% sensitivity) and CD148 (>1.1; 100% sensitivity, 90% sensitivity) were useful for differentiating blastoid-mantle cell lymphoma/MCL from diffuse large B cell lymphoma; while CD148MFI (≥20.25), CD148 (>3.35) and CD148 (>0.95) showed >90% specificity and sensitivity for distinguishing MCL from CLL. Pairwise analysis also showed a good discriminant function of various parameters for distinguishing SMZL from other MBNs like FL, MCL as well as CLL.

Conclusions: The current study shows an excellent utility of CD148MFI, CD180MFI, their ratio and relative expression levels in the subcategorization of immunophenotypically related MBNs.
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http://dx.doi.org/10.1111/ijlh.13467DOI Listing
January 2021

Evaluation of a flow cytometric test for G6PD-deficient erythrocytes.

Trop Med Int Health 2021 04 2;26(4):462-468. Epub 2021 Feb 2.

Department of Hematology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Objective: Glucose-6-phosphate dehydrogenase (G6PD) deficiency, an X-linked recessive disorder, is the commonest erythrocytic enzymopathy worldwide. Reliable diagnosis and severity prediction in G6PD-deficient/heterozygous females remain challenging. A recently developed flow cytometric test for G6PD deficiency has shown promise in precisely identifying deficient females. This paper presents our experiences with this test in a subtropical setting and presents a modification in flow cytometric data acquisition strategy.

Methods: The methaemoglobin reduction + ferryl Hb generation-based flow cytometric G6PD test was compared with the screening methaemoglobin reduction test (MRT) and confirmatory G6PD enzyme activity assay (EAA) in 20 G6PD-deficient males, 22 G6PD-heterozygous/deficient females and 20 controls. Stained cells were also assessed for bright/dim G6PD activity under a fluorescent microscope.

Results: Flow cytometry separated and quantified %bright cells in heterozygous/deficient females, objectively classifying them into 6 normal (>85% bright cells), 14 intermediate (10-85%) and two G6PD-deficient (<10% bright cells). Concordance with MRT was 89% (55/62 cases) and with EAA was 77% (48/62 cases). Fluorometrically predicted violet laser excitation (405-nm) with signal acquisition in the 425-475 nm region was a technical advancement noted for the first time in this paper.

Conclusion: Flow cytometry/fluorescence microscopy represent technically straightforward methods for the detection and quantification of G6PD-deficient erythrocytes. Based on our results, we recommend their application as a first-line investigation to screen females who are prescribed an oxidant drug like primaquine or dapsone.
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http://dx.doi.org/10.1111/tmi.13547DOI Listing
April 2021

Clericuzio-type poikiloderma with neutropenia in a patient from India.

Am J Med Genet A 2021 01 27;185(1):278-281. Epub 2020 Oct 27.

Department of Dermatology, Venereology and Leprology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

A 9-year-old boy presented for evaluation of variegated skin pigmentation. Palms and soles revealed honeycombed hyperpigmented hyperkeratosis. Irregular, firm, skin coloured nodules suggestive of cutaneous calcification were present on both elbows. Total leucocyte count and absolute neutrophil count were 3720/mm3 and 420/mm3 respectively. The neutropenia was not cyclical. Systematic analysis of the whole exome data revealed a homozygous mutation in USB1 gene; chr16:g.58043892TA>-[1/1]. A final diagnosis of poikiloderma with neutropenia- Clericuzio type (PNC) was made. Naegeli Franceschetti Jadassohn, dermatopathia pigmentosa reticularis, PNC and dyskeratosis congenita, all can present with overlapping cutaneous manifestations. Subtle clinical details like thickened nails, hyperextensible joints, calcinosis cutis, characteristic facies and a preceding erythematopapular rash strongly favor the diagnosis of PNC. The index case highlights two novel findings: obliterated dermatoglyphics and mucin deposition (features not described hitherto in PNC).
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http://dx.doi.org/10.1002/ajmg.a.61943DOI Listing
January 2021

Molecular Characterization of G6PD Deficiency at a North Indian Centre: Implications for Diagnostic Testing Laboratories in Different Regions of India.

Indian J Hematol Blood Transfus 2020 Oct 1;36(4):766-768. Epub 2020 Apr 1.

Department of Hematology, Level 5, Research Block A, Postgraduate Institute of Medical Education and Research, Sector 12, Chandigarh, India.

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http://dx.doi.org/10.1007/s12288-020-01275-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7573081PMC
October 2020

Hemolytic erythrocytosis: an amalgamated phenotype from coinherited Chuvash polycythemia and G6PD Kerala-Kalyan with acquired transient stomatocytosis.

Ann Hematol 2021 Aug 8;100(8):2107-2109. Epub 2020 Oct 8.

Department of Hematology, Postgraduate Institute of Medical Education and Research, Sector 12, Chandigarh, 160012, India.

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http://dx.doi.org/10.1007/s00277-020-04295-wDOI Listing
August 2021

A high frequency of Gilbert syndrome (UGT1A1*28/*28) and associated hyperbilirubinemia but not cholelithiasis in adolescent and adult north Indian patients with transfusion-dependent β-thalassemia.

Ann Hematol 2020 Sep 16;99(9):2019-2026. Epub 2020 Jul 16.

Department of Hematology, PGIMER, Level 5, Research Block A, Sector 12, Chandigarh, 160012, India.

Hyperbilirubinemia and pigment gallstones are frequent complications in transfusion-dependent β-thalassemia (TDβT) patients. Bilirubin production and clearance are determined by genetic as well as environmental variables like ineffective erythropoiesis, hemolysis, infection-induced hepatic injury, and drug- or iron-related toxicities. We studied the frequency of the Gilbert syndrome (GS), a common hereditary cause of hyperbilirubinemia in 102 TDβT patients aged 13-43 years (median 26 years). Total and unconjugated hyperbilirubinemia were frequent (81.4% and 84.3% patients respectively). Twenty (19.6%) patients showed total bilirubin > 3.0 mg/dL; 53 (51.9%) had an elevation of either alanine or aspartate aminotransferase, or alkaline phosphatase liver enzymes. Nineteen (18.6% of the 92 tested) were positive for hepatitis B or C, or HIV. The mean total and unconjugated bilirubin levels and AST, ALT, and ALP levels in patients positive for hepatitis B or C were not significantly different from negative cases. Eighteen patients (17.7%) had GS: homozygous (TA)7/7 UGT1A1 promoter motif (the *28/*28 genotype), 48 (47.1%) were heterozygous (TA)6/7. Total + unconjugated bilirubin rose significantly with the (TA)7 allele dose. Fourteen (13.7%) patients had gallstones. There was no significant difference in total/unconjugated bilirubin in patients with/without gallstones and no significant differences in frequencies of gallstones within the three UGT1A1 genotypes. This largest study in Indian TDβT patients suggests that GS should be excluded in TDβT cases where jaundice remains unexplained after treatable causes like infections, chelator toxicity, or transfusion-related hemolysis are excluded. GS was not associated with gallstones, possibly due to a lower incidence of cholelithiasis overall, a younger age cohort, or other environmental factors.
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http://dx.doi.org/10.1007/s00277-020-04176-2DOI Listing
September 2020

A flow cytometric cell-cycle assay using methyl green.

Anal Biochem 2020 07 22;601:113782. Epub 2020 May 22.

Department of Hematology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Methyl green (MG), a conventional, low-cost histological stain, was used to design a flow cytometric cell-cycle/DNA-ploidy assay. On fluorometry, MG absorbed maximally at 633-nm, showed negligible fluorescence in free-state, but emitted brightly when bound to DNA. Optimal dye and cell concentrations for staining and effects of time and photobleaching on stained cells were determined for a lyse-permeabilize-stain protocol. Linearity of DNA-binding, coefficients-of-variation of G0/G1-peaks and minimal carryover were confirmed. Assay results correlated highly with a propidium iodide-based kit in 29 acute lymphoblastic leukemia specimens. The MG-based DNA-ploidy assay represented an accurate and inexpensive alternative to conventional PI-based assays.
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http://dx.doi.org/10.1016/j.ab.2020.113782DOI Listing
July 2020

Missing Hb Q-India Peak in a Triple-Heterozygous Patient with Hb D-Punjab/Hb Q-India/β-Thalassemia Trait.

Hemoglobin 2020 May 25;44(3):211-213. Epub 2020 May 25.

Departments of Hematology, Postgraduate Institute of Medical Education and Research, Chandigarh (Union Territory), India.

Interpretation of variant hemoglobins (Hbs) can pose challenges. We describe a puzzling case with multiple variant Hb peaks that was solved by family studies. A 32-year-old female with anemia and jaundice underwent cation exchange high performance liquid chromatography (HPLC), which revealed near-absence of Hb A along with variant peaks in the D- and C-windows (78.9 and 13.3%, respectively) and normal range of Hb F. As the HPLC did not fit any known pattern, family screening was performed. Her mother was heterozygous for Hb D-Punjab (: c.364G>C) and Hb Q-India (: c.193G>C) with the hybrid α/β eluting in the C-window on HPLC. Her sister had β-thalassemia (β-thal) trait, while her brother was heterozygous for Hb Q-India. In view of the family study results, the index case was interpreted as a double heterozygote for Hb D-Punjab and β-thal with coinherited Hb Q-India. The Hb Q-India peak [retention time (RT) 4.7 min.] was absent on her HPLC as there were no normal β-globin chains available to bind with the α chains. To the best of our knowledge, such an HPLC pattern with a missing Q-India peak, despite having inherited the α variant, has not been previously reported. This case illustrates the importance of family screening as an inexpensive and rapid method to resolve difficult and unusual HPLC patterns.
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http://dx.doi.org/10.1080/03630269.2020.1767128DOI Listing
May 2020

Paratrabecular myelofibrosis and occult mastocytosis are strong morphological clues to suspect translocation in hypereosinophilia.

Indian J Hematol Blood Transfus 2020 Apr 4;36(2):384-389. Epub 2019 Dec 4.

1Department of Hematology, Post Graduate Institute of Medical Education and Research, 5th floor, Research block A, Chandigarh, 160012 India.

To study the clinico-haematological and histopathological characteristics of rearranged hypereosinophilia/hypereosinophilic syndrome (F/P+ve HE/HES), a retrospective analysis of patients with F/P+ve HE diagnosed over a period of 43 months was performed. Peripheral blood smears, bone marrow aspirate (BMA) and biopsies (BMB) were reviewed in each case and; reticulin stain and immunohistochemistry for mast cell tryptase (MCT) and CD117 was performed. F/P+ve HE was diagnosed in a total of ten patients during study period. All patients were males with a median age of 36 years (23-44 years). The median duration of presenting complaints was 7 months (2 months-3 years) which included specific symptoms related to various organs (80% of cases). Anaemia, thrombocytopenia and splenomegaly were seen in 60%, 50% and 90% of the cases respectively. Mastocytosis was not obvious in BMA but identified by MCT on BMB in all cases. Myelofibrosis (grade ≥ 1) was seen in 80% of the cases and includes multifocal paratrabecular fibrosis in 50% of the biopsies. Our study shows that bone marrow mastocytosis and myelofibrosis are very useful morphological indicators to suspect F/P+ve HE and suggests the routine use of reticulin staining and MCT immunohistochemistry in all BMBs performed for the evaluation of HE/HES.
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http://dx.doi.org/10.1007/s12288-019-01236-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7229073PMC
April 2020

A decision support scheme for beta thalassemia and HbE carrier screening.

J Adv Res 2020 Jul 24;24:183-190. Epub 2020 Apr 24.

Department of Materials and Production, Aalborg University, DK 9220 Aalborg, Denmark.

The most effective way to combat β-thalassemias is to prevent the birth of children with thalassemia major. Therefore, a cost-effective screening method is essential to identify β-thalassemia traits (BTT) and differentiate normal individuals from carriers. We considered five hematological parameters to formulate two separate scoring mechanisms, one for BTT detection, and another for joint determination of hemoglobin E (HbE) trait and BTT by employing decision trees, Naïve Bayes classifier, and Artificial neural network frameworks on data collected from the Postgraduate Institute of Medical Education and Research, Chandigarh, India. We validated both the scores on two different data sets and found 100% sensitivity of both the scores with their respective threshold values. The results revealed the specificity of the screening scores to be 79.25% and 91.74% for BTT and 58.62% and 78.03% for the joint score of HbE and BTT, respectively. A lower Youden's index was measured for the two scores compared to some existing indices. Therefore, the proposed scores can obviate a large portion of the population from expensive high-performance liquid chromatography (HPLC) analysis during the screening of BTT, and joint determination of BTT and HbE, respectively, thereby saving significant resources and cost currently being utilized for screening purpose.
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http://dx.doi.org/10.1016/j.jare.2020.04.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7186556PMC
July 2020

Congenital dyserythropoietic anemia type IV with high fetal hemoglobin caused by heterozygous KLF1 p.Glu325Lys: first report in an Indian infant.

Ann Hematol 2021 Jan 27;100(1):281-283. Epub 2020 Mar 27.

Department of Hematology, Post Graduate Institute of Medical Education and Research, Chandigarh, 160012, India.

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http://dx.doi.org/10.1007/s00277-020-03982-yDOI Listing
January 2021

Marburg I Polymorphism (G511E) in Adults with Deep Vein Thrombosis.

Indian J Hematol Blood Transfus 2020 Jan 12;36(1):183-186. Epub 2019 Jun 12.

3Department of Internal Medicine, Postgraduate Institute of Medical Education and Research, Sector 12, Chandigarh, 160012 India.

The Marburg I polymorphism (G511E) in gene was listed as one of the risk factor for idiopathic DVT among the western population. The frequency of Marburg I polymorphism in India is presently not known. Fifty DVT cases and 50 healthy controls were tested for Marburg I polymorphism using ARMS-PCR technique. The thrombophilic risk factors (Protein C, Protein S, Antithrombin III, Factor V Leiden and antiphospholipid antibodies) were also determined. Marburg I polymorphism (heterozygous) was found in 2 patients (4%) but not in control subjects. These two cases did not have any other thrombophilia markers. Among the thrombophilic markers, heterozygous FVL mutation, PS, PC, AT deficiencies and antiphospholipid antibodies were seen in 10%, 10%, 6%, 6% and 8% of the patients respectively. The controls showed only the presence of antiphospholipid antibodies in 6% of subjects. Marburg I polymorphism among Indians DVT patients was determined for the first time. Its incidence was found in 4% of cases and not in controls. Although not statically significant this may be considered as one of the contributory risk factors for the development of DVT. A larger study is required for the validation of data.
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http://dx.doi.org/10.1007/s12288-019-01146-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7042457PMC
January 2020

Hb Rush (: c.304G>C): A Rare Variant Hemoglobin Mimicking the Hb S (: c.20A>T) Variant on High Performance Liquid Chromatography.

Hemoglobin 2020 Jan 3;44(1):64-66. Epub 2020 Mar 3.

Department of Obstetrics and Gynaecology, Christian Medical College and Hospital, Ludhiana, India.

High performance liquid chromatography (HPLC) is a useful and rapid tool in the evaluation of hemoglobin (Hb) disorders that include thalassemia and various hemoglobinopathies. Most of the techniques or programs used in automated testing platforms are customized to identify the common variants seen in that particular region. At times, variant Hbs may be identified which are not commonly seen in the local population. This may cause diagnostic dilemma and may require further studies for definitive characterization. We present a patient with Hb Rush (: c.304G>C), a rare unstable Hb variant eluting in the Hb S (: c.20A>T) window on HPLC.
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http://dx.doi.org/10.1080/03630269.2020.1733009DOI Listing
January 2020

Next-Generation Sequencing-Based Diagnosis of Unexplained Inherited Hemolytic Anemias Reveals Wide Genetic and Phenotypic Heterogeneity.

J Mol Diagn 2020 04 6;22(4):579-590. Epub 2020 Feb 6.

Department of Hematology, Post Graduate Institute of Medical Education and Research, Chandigarh, India. Electronic address:

Determination of the cause of inherited hemolysis is based on clinical and stepwise conventional laboratory tests. Patients with obscure etiology require genetic diagnosis, which is time-consuming, expensive, and laborious, mainly because of numerous causal genes. This study enrolled 43 patients with clinical and laboratory evidence of unexplained hemolytic anemia. Initially, 13 patients were tested using a commercial (TruSight One) panel, and remaining cases underwent targeted sequencing using a customized 55-gene panel. Pyruvate kinase deficiency was found in eight, glucose-6-phosphate dehydrogenase (G6PD) deficiency in three (G6PD Guadalajara in two and p.Tyr227Ser: novel, named as G6PD Chandigarh), and glucose-6-phosphate isomerase (GPI) deficiency in two (GPI:p.Arg347His and p.Phe304Leu: novel, named as GPI Chandigarh). Three patients had Mediterranean stomatocytosis/macrothrombocytopenia, and two had overhydrated stomatocytosis. Xerocytosis was found in three patients, whereas six had potentially pathogenic variants in membrane protein-coding genes. Overall, 63% cases received a definite diagnosis. Timely determination of etiology was helpful in diagnosis, genetic counseling, and offering a prenatal diagnosis. Therapeutic implications include performing or avoiding splenectomy that may ameliorate the anemia in many but also predispose to thrombosis in other groups of patients. This first study on the genetic spectrum of unexplained hemolytic anemia from the Indian subcontinent also represents, currently, one of the largest cohort worldwide of such patients.
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http://dx.doi.org/10.1016/j.jmoldx.2020.01.007DOI Listing
April 2020

HbH disease due to compound heterozygosity for hemoglobins Zürich-Albisrieden and Sallanches.

Pediatr Blood Cancer 2020 04 13;67(4):e28161. Epub 2020 Jan 13.

Department of Hematology, Postgraduate Institute of Medical Education & Research, Chandigarh, India.

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http://dx.doi.org/10.1002/pbc.28161DOI Listing
April 2020

Phenotypic and genetic heterogeneity arising from a novel substitution at amino acid position Val205 in GATA1 related X-linked thrombocytopenia with dyserythropoietic anemia.

Blood Cells Mol Dis 2020 03 30;81:102391. Epub 2019 Nov 30.

Department of Hematology, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India. Electronic address:

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http://dx.doi.org/10.1016/j.bcmd.2019.102391DOI Listing
March 2020

Laboratory Approach to Hemolytic Anemia.

Indian J Pediatr 2020 01 10;87(1):66-74. Epub 2019 Dec 10.

Department of Hematology, Post Graduate Institute of Medical Education and Research, Chandigarh, 160012, India.

Hemolytic anemias are a group of disorders with varied clinical and molecular heterogeneity. They are characterized by decreased levels of circulating erythrocytes in blood. The pathognomic finding is a reduced red cell life span with severe anemia or, compensated hemolysis accompanied by reticulocytosis. The diagnostic workup or laboratory approach for hemolytic anemias is based on methodical step-wise testing which includes red blood cell morphology, hematological indices with increased reticulocyte count along with clinical features of hemolytic anemias. If conventional laboratory tests are unable to detect the underlying cause of hemolysis, genetic testing is recommended. Sanger sequencing along with conventional testing is the most efficient way to diagnose the underlying genetic causes, especially in thalassemias/hemoglobinopathies, if required. However, hemolytic anemias being highly heterogeneous disorders, next-generation sequencing-based screening is rapidly becoming an efficient way to decipher the etiologies where common causes have been excluded.
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http://dx.doi.org/10.1007/s12098-019-03119-8DOI Listing
January 2020
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