V S Nadarajan

University of Malaya, Kuala Lumpor, Kuala Lumpur, Malaysia

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Publications (20)30.03 Total impact

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    ABSTRACT: Non-HLA gene polymorphisms have been shown to be associated with the risk of graft-versus-host disease (GVHD) and outcome of allogeneic haematopoietic stem cell transplantation (AHSCT). This study aims to investigate the role of IL6, TNFα, IL10, IL2 and IL12 gene polymorphisms in the outcome of AHSCT in a South East Asian population. A total of 67 patients and 59 donors who underwent HLA-identical matched sibling AHSCT were available for analysis. There was no significant association between the different cytokine genotypes of patients with the incidence and severity of acute GVHD. Patients with IL2 166∗T allele and patients who received donor stem cells who had IL2 166∗G allele appeared to have reduced incidence of cGVHD. Patients who received donor stem cells with IL12 1188∗C allele are found to be associated with better disease free survival. These results suggest a possible role of IL2 and IL12 gene polymorphisms in the outcome of AHSCT in a South East Asian population.
    No preview · Article · Feb 2016 · Cytokine
  • V. S. Nadarajan

    No preview · Article · Jul 2013 · ISBT Science Series
  • V.S. Nadarajan
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    ABSTRACT: Autoimmune haemolytic anaemia (AIHA) occurs as a result of antibodies directed against self-red blood cell (RBC) antigens, leading to the premature destruction of RBC. RBC destruction may occur within the vasculature, often mediated by the membrane-lysing complex, which is generated upon complement activation or occur extravascularly, within the reticulo-endothelial system that expresses FcγR and C3 receptors that bind antibody and complement coated RBC. The laboratory hallmark of AIHA is a positive direct antiglobulin test (DAT) although it has to be recognized that occasional cases of DAT-negative AIHA may occur. Secondary causes for AIHA such as an underlying autoimmune disorder, infections or malignancies should be considered as part of the investigation process for AIHA.Immunohaematology investigations for AIHA should always include a DAT using monospecific anti-IgG and anti-C3d. On occasions, further testing with anti-IgA or -IgG subtypes may be necessary. While the DAT provides information on bound RBC antibodies, the indirect antiglobulin test (IAT) using screening and antibody identification cells will provide information on the specificity of circulating antibody. Often this will give a pan-reactive pattern although it is not unusual to identify coincident autoantibodies with defined red cell specificity. Negative IAT with screening and identification cells in the presence of a positive DAT should raise suspicion of drug-induced AIHA. In patients who may have been potentially alloimmunized, further procedures should be performed to exclude the coincident presence of alloantibodies as failure to recognize alloantibodies may result in an immediate or delayed haemolytic transfusion reaction if red cell transfusions are initiated. Elution and auto- or allo-adsorbtion techniques are useful to separate allo- and autoantibodies. Complete red cell phenotyping should be concurrently performed to aid in identifying antibody specificities. Heavily antibody-coated red cells may be difficult to phenotype with some anti-sera, in which case, molecular based red cell genotyping should be initiated. Molecular based red cell typing is also particularly useful where the patient has recently been transfused and the initial red cell phenotype of the patient is not known.The primary management of the patient with AIHA is amelioration of the underlying condition and suppression of immune mediated haemolysis. This is usually achieved with administration of steroids or immunosuppressive agents. Splenectomy may be an effective second line treatment. Rituximab is increasingly becoming an effective treatment option in patients who are steroid-refractory and not suitable for splenectomy.Red cell transfusions in patients with AIHA should be undertaken carefully although they should never be denied blood transfusions because of inability to find compatible units. As far as possible, phenotype matched red cells, cross-match compatible with the patient's autoadsorbed serum should be transfused. If coincident alloantibodies are identified, antigen-negative red cells will need to be selected.
    No preview · Article · Jul 2013 · ISBT Science Series
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    Full-text · Article · Feb 2013 · Vox Sanguinis
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    ABSTRACT: Acute promyelocytic leukemia with concurrent myeloid sarcoma is a rare clinical event. Herein we describe a patient that presented with back pain and bilateral leg weakness caused by spinal cord compression due to extramedullary deposition of leukemic cells. Acute promyelocytic leukemia was suspected based on immunophenotypic findings of malignant cells in bone marrow aspirate. The diagnosis was confirmed by the presence of PML-RARα fusion copies. MRI showed multiple hyperintense changes on the vertebral bodies, together with intraspinal masses causing spinal cord compression. The patient immediately underwent radiotherapy, and was treated with all-trans retinoic acid and idarubicin. Reassessment MRI showed complete resolution of all intraspinal masses and the disappearance of most of the bony lesions. Post-treatment bone marrow aspirate showed complete hematological and molecular remission. The motor power of his legs fully recovered from 0/5 to 5/5; however, sensory loss below the T4 level persisted.
    Full-text · Article · Sep 2012 · Turkish Journal of Haematology
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    Jia-Yi Tan · Lay-Hoong Lian · Veera Sekaran Nadarajan
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    ABSTRACT: Human platelet antigens (HPA) are determinant in several platelet-specific alloimmune disorders, such as neonatal alloimmune thrombocytopenia, post-transfusion purpura and platelet transfusion refractoriness. The distribution of HPA systems in the Malaysian population is not known. Defining the patterns of HPA systems provides a basis for risk assessment and management of the above complications. The aim of this study was to investigate the distribution of HPA -1 to -6 and -15 in the three major ethnic groups (Malay, Chinese and Indian) in the Malaysian population. A total of 600 random donor samples, 200 from each of the three ethnic groups, were genotyped by means of real time polymerase chain reaction (PCR) with hydrolysis probes and PCR-restriction fragment length polymorphism (PCR-RFLP). The most common genotype observed in this study was HPA-1a/1a-2a/2a-3a/3b-4a/4a-5a/5a-6a/6a-15a/15b (17%) followed by HPA-1a/1a-2a/2a-3a/3a-4a/4a-5a/5a-6a/6a-15a/15b (14.33%). The allele frequencies of HPA in Malays and Chinese were found to be similar those of other East and South-East Asian populations, while those of Indians were comparable to the frequencies found in Europeans. The results of this study have been useful for determining the distribution of HPA polymorphisms in this region and for potential clinical implications.
    Full-text · Article · May 2012 · Blood transfusion = Trasfusione del sangue
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    V. S. Nadarajan

    Preview · Article · Oct 2011 · ISBT Science Series
  • Veera S Nadarajan · Chow-Hiang Ang · Ping-Chong Bee
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    ABSTRACT: We investigated the role of lipocalin-2 (LCN-2) and its receptor (SLC22A17) in mediating clonal dominance in a patient with both BCR-ABL and JAK2-V617F mutations. LCN-2 mRNA showed a near 50-fold increase in expression, accompanied by down-regulation of SLC22A17, coinciding with increase in BCR-ABL transcripts, loss of JAK2-V617F and change of clinical phenotype from polycythaemia vera to chronic myeloid leukaemia. These changes were reversed after commencing imatinib mesylate. Consistent with experimental studies, BCR-ABL+ cells express LCN-2 leading to suppression of BCR-ABL- cells and explain their eventual dominance when occurring together with JAK2-V617F.
    No preview · Article · Sep 2011 · European Journal Of Haematology
  • V S Nadarajan · A A Laing · S M Saad · M Usin
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    ABSTRACT: Appropriate screening for irregular red-cell antibodies is essential for ensuring transfusion compatibility and for antenatal management of mothers at risk of haemolytic disease of the foetus and newborn. Screening for all relevant antibodies is, however, limited by screening cells that do not express antigens present in the patient and donor population. Technology to artificially incorporate antigens into red cells is currently available and may be an option for customizing screening cells. We sought to identify retrospectively the changing patterns of alloantibody prevalence in our multiethnic population on change of screening cells. Antibody screening records of 143 501 patients tested from 2004 to 2010 were retrieved and divided into two groups: period-1 (2004-2008) and period-2 (2009-2010). During period-1, standard screening cells were used while in period-2, MUT+Mur+ KODE(™) transformed red cells (kodecytes) were used. Four per cent of samples tested during period-2 were positive on antibody screening compared to 3·2% in period-1. Specific antibodies, excluding anti-D, were identified in 1·66% and 1·52% of patients in period-2 and -1, respectively. When confined to antibodies of clinical significance only, period-2 showed higher alloantibody prevalence of 1·16% as compared to 0·66% in period-1. Antibodies to glycophorin variants of MNS (vMNS) were more commonly detected while antibodies to Lewis antigens declined during period-2.   Antibodies to vMNS antigens are common in South and East Asian populations and are often missed when using standard screening cells. Use of specifically engineered screening cells to express red-cell antigens artificially is beneficial in detecting the diverse alloantibodies present in our population.
    No preview · Article · May 2011 · Vox Sanguinis
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    ABSTRACT: The glucose-6-phosphate dehydrogenase (G6PD) fluorescent spot test (FST) is a useful screening test for G6PD deficiency, but is unable to detect heterozygote G6PD-deficient females. We sought to identify whether reporting intermediate fluorescence in addition to absent and bright fluorescence on FST would improve identification of mildly deficient female heterozygotes. A total of 1266 cord blood samples (705 male, 561 female) were screened for G6PD deficiency using FST (in-house method) and a quantitative enzyme assay. Fluorescence intensity of the FST was graded as either absent, intermediate or normal. Samples identified as showing absent or intermediate fluorescence on FST were analysed for the presence of G6PD mutations using TaqMan@SNP genotyping assays and direct nucleotide sequencing. Of the 1266 samples, 87 samples were found to be intermediate or deficient by FST (49 deficient, 38 intermediate). Of the 49 deficient samples, 48 had G6PD enzyme activity of ≤ 9.5 U/g Hb and one sample had normal enzyme activity. All 38 intermediate samples were from females. Of these, 21 had G6PD activity of between 20% and 60%, and 17 samples showed normal G6PD activity. Twenty-seven of the 38 samples were available for mutation analysis of which 13 had normal G6PD activity. Eleven of the 13 samples with normal G6PD activity had identifiable G6PD mutations. Glucose-6-phosphate dehydrogenase heterozygote females cannot be identified by FST if fluorescence is reported as absent or present. Distinguishing samples with intermediate fluorescence from absent and bright fluorescence improves detection of heterozygote females with mild G6PD deficiency. Mutational studies confirmed that 85% of intermediate samples with normal enzyme activity had identifiable G6PD mutations.
    No preview · Article · Apr 2011 · International journal of laboratory hematology
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    Veera Sekaran Nadarajan · Chow-Hiang Ang · Mohamed Kamil Syed-Sultan · Ping-Chong Bee

    Full-text · Article · Mar 2011 · Annals of Hematology
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    ABSTRACT: The outcome of treating chronic myeloid leukemia (CML) with imatinib mesylate (IM) is inferior when therapy is commenced in late chronic or accelerated phase as compared to early chronic phase. This may be attributed to additional genomic alterations that accumulate during disease progression. We sought to identify such lesions in patients showing suboptimal response to IM by performing array-CGH analysis on 39 sequential samples from 15 CML patients. Seventy-four cumulative copy number alterations (CNAs) consisting of 35 losses and 39 gains were identified. Alterations flanking the ABL1 and BCR genes on chromosomes 9 and 22, respectively, were the most common identified lesions with 5 patients losing variable portions of 9q34.11 proximal to ABL1. Losses involving 1p36, 5q31, 17q25, Y and gains of 3q21, 8q24, 22q11, Xp11 were among other recurrent lesions identified. Aberrations were also observed in individual patients, involving regions containing known leukemia-associated genes; CDKN2A/2B, IKZF1, RB1, TLX1, AFF4. CML patients in late stages of their disease, harbor pre-existing and evolving sub-microscopic CNAs that may influence disease progression and IM response.
    Full-text · Article · Mar 2011 · International journal of hematology
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    CL Phan · CH Ang · KL Liang · GG Gan · Z Zakaria · V Nadarajan
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    ABSTRACT: Background. Chronic myeloid leukemia (CML) is associated with the presence of the Philadelphia chromosome (Ph), t(9;22)(q34;q11), leading to the expression of the aberrant tyrosine kinase fusion protein, BCR-ABL. The tyrosine kinase inhibitor, imatinib mesylate (IM), is the current standard frontline therapy for newly diagnosed CML and it has significantly improved the prognosis of these patients. In some patients, IM therapy is however complicated by the emergence of resistance particularly in more advanced phase of CML. Several mechanisms of resistance to IM have been demonstrated, including tyrosine kinase domain (TKD) mutations, amplification and overexpression of BCR-ABL gene and clonal evolution. It has become apparent that multiple factors driven by genomic alterations and mutations would contribute to IM resistance. Aims. Our study aimed to identify recurrent genomic aberrations in addition to TKD mutations which could contribute to poor response to IM, primarily utilising array comparative genomic hybridization analysis (aCGH). Methods. DNA and RNA samples were extracted from 165 archived cells lysates collected at different time points from 37 CML patients. All patients had prior information on response to IM based on clinical, cytogenetics and BCR-ABL transcript levels. Only 103 samples were however of adequate RNA quality for TKD mutation analysis. Sixteen patients with suboptimal response to IM were subsequently identified (4 with TKD mutations and 12 without), and their 40 serial DNA samples were subjected to aCGH analysis using human genome CGH microarray 44K chips (Agilent Technologies) at a resolution of 1Mbp. Intensity data between the test and reference was processed using Feature Extraction Image Analysis Software. Confirmation by fluorescence in situ hybridization (FISH) using corresponding commercial probe was carried out depending on availability of metaphase cells preparations. Results. One of 40 samples showed poor quality of the test and was excluded from the study. Lesions were detected by aCGH in all studied patients at least on one time point. The most common genomic losses included the regions at 1p36, 1q31, 2q21, 9q34, 21q, -Y and gains at 8q24, 9q34, 14q, 16p and 22q11. Multiple genomic aberration involving gain of 8q24, losses of 9q24 and 22q11, and loss of ASS gene simultaneously were detected in one of the patient that co-harbored multiple TKD mutations (Y253F; Y253F/F359V/1023G>A). Gain of 8q24 was also noted in serial samples from 2 other patients, one of whom had a G250E TKD mutation. All patients with 8q24 gain showed progressive disease and short survival. Conclusion. Our findings show that multiple cryptic unbalanced genomic aberrations occur in patients with suboptimal response to IM. We were however unable to unequivocally show any single recurrent aberration that was associated with IM resistance although certain lesions, in particular, gains of 8q24 is associated with rapid disease progression of CML.
    Full-text · Conference Paper · Jun 2010
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    ABSTRACT: A critical aspect of blood transfusion is the timely provision of high quality blood products. This task remains a significant challenge for many blood services and blood systems reflecting the difficulty of balancing the recruitment of sufficient donors, the optimal utilization of the donor's gift, the increasing safety related restrictions on blood donation, a growing menu of specialized blood products and an ever-growing imperative to increase the efficiency of blood product provision from a cost perspective. As our industry now faces questions about our standard practices including whether or not the age of blood has a negative impact on recipients, it is timely to take a look at our collective inventory management practices. This International Forum represents an effort to get a snap shot of inventory management practices around the world, and to understand the range of different products provided for patients. In addition to sharing current inventory management practices, this Forum is intended to foster an exchange of ideas around where we see our field moving with respect to various issues including specialty products, new technologies, and reducing recipient risk from blood transfusion products.
    Full-text · Article · Apr 2010 · Vox Sanguinis
  • Ping Chong Bee · G G Gan · V S Nadarajan · N A Latiff · N Menaka
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    ABSTRACT: The co-occurrence of JAK2 V617F mutation with BCR-ABL reciprocal translocation is uncommon. We report a 60-year-old man who initially presented with phenotype of polycythemia vera (PV), which evolved into chronic myeloid leukemia and back to PV once treatment with imatinib was commenced. JAK2 V617F mutation and BCR-ABL fusion transcripts were detected in the initial sample. However, JAK2 V617F alleles diminished when BCR-ABL mRNA burden increased and reappeared once the patient was commenced on imatinib. The dynamic interaction between JAK2 V617F and BCR-ABL implies that two independent clones exist with the JAK2 V617F clone only achieving clonal dominance when BCR-ABL positive clones are suppressed by imatinib.
    No preview · Article · Jan 2010 · International journal of hematology
  • V S Nadarajan · P Sthaneshwar · S Jayaranee
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    ABSTRACT: Individuals with alpha-thalassaemia (ATT), beta-thalassaemia (BTT) and HbE trait (HET) are often initially identified based on haematological parameters. However, the values of these parameters usually overlap with iron deficiency anaemia (IDA) and anaemia of chronic disease (ACD). We evaluated the use of RBC-Y in 156 normal individuals and 332 patients; ATT (n = 37), BTT (n = 61), HET (n = 25), HbH disease (n = 5), ACD (n = 67), IDA (n = 83) and ACD with IDA (n = 54). Diagnostic efficiency was analysed by receiver operating characteristics (ROC). MCH was better compared with RBC-Y in discriminating normal from abnormal with sensitivity and specificity of 94% at a cut-off of 26 pg. The Green and King (G&K) index performed the best in discriminating carriers from IDA and ACD with area under the ROC curve (AUC(ROC)) of 0.81. However, if ACD was excluded, RBC-Y/MCV was a good discriminator for carriers from IDA with AUC(ROC) = 0.845. In general screening of populations with ATT, BTT and HET, we propose that hypochromic individuals be first identified by MCH <26 pg and carriers distinguished within these hypochromic individuals from IDA by using RBC-Y/MCV. However, if the prevalence of ACD were high within the screening population, G&K index would be a more suitable discriminator.
    No preview · Article · Jul 2009 · International journal of laboratory hematology
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    Hemalatha Shanmugam · Geok Im Eow · Veera Sekaran Nadarajan
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    ABSTRACT: Adult T-cell leukaemia/lymphoma (ATLL) is a rare T lymphoproliferative disorder which is aetiologically linked with human T-cell lymphotropic virus type-1 (HTLV-1). HTLV-1 is endemic in Japan, Caribbean and Africa. The highest incidence of ATLL is in Japan although sporadic cases have been reported elsewhere in the world. We describe a case of ATLL with an unusual presentation which we believe is the first reported case of ATLL in Malaysia based on our literature search. A 51-year-old Indian lady was referred to University Malaya Medical Centre for an incidental finding of lymphocytosis while being investigated for pallor and giddiness. Clinical examination revealed bilateral shotty cervical lymph nodes with no hepato-splenomegaly or skin lesions. Laboratory investigations showed absolute lymphocytosis (38 x 10(9)/L) with a mildly increased serum lactate dehydrogenase. The peripheral blood smear showed the presence of predominantly small to medium sized, non-flower lymphocytes. The bone marrow showed similar findings of prominent lymphocytosis. Immunophenotyping of the bone marrow mononuclear cells showed CD3+, CD4+, CD5+, CD7- and CD25+ which is characteristic of ATLL phenotype. HTLV-1 infection was confirmed by the presence of HTLV-1 proviral DNA in the tumor cells using conventional Polymerase Chain Reaction (PCR) and real-time PCR. Here, we discuss the pathogenesis and characteristics of ATLL as well as the detection of HTLV-1 by real time PCR.
    Preview · Article · Jul 2009 · The Malaysian journal of pathology
  • V S Nadarajan · C H Ooi · P Sthaneshwar · M W Thompson
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    ABSTRACT: Altitude training is sometimes employed by elite endurance athletes to improve their sea level performance. This improvement results from the increased red cell mass consequent upon the boost in erythropoietin (EPO) level that occurs as a response to the relatively hypoxic environment at high altitudes. We measured serum EPO levels together with various red cell and reticulocyte parameters including immature reticulocyte fraction (IRF) in eight national track-endurance cyclists, resident at sea-level, prior to and upon return from an altitude of approximately 1905 m. Reticulocytes and soluble transferrin receptor (sTfR) were significantly increased with reduction in ferritin levels immediately on return from high altitude indicating increased erythropoietic activity. IRF in particular showed a significant peak immediately on return but decline to sub-baseline levels by day 9, and recovery to baseline by day 16. Our results indicate that IRF is a sensitive marker of erythropoietic status in athletes undergoing altitude training and subsequent loss of EPO stimuli on return to sea level.
    No preview · Article · Feb 2009 · International journal of laboratory hematology
  • V Nadarajan · P Sthaneshwar · G I Eow
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    ABSTRACT: The objective of this study was to identify haematological parameters useful in screening for iron deficiency among blood donors. Iron deficiency is a common complication of blood donation and often goes unrecognized until anaemia develops. Biochemical markers such as soluble transferrin receptor (TfR), ferritin and log(TfR/F) have been proposed as more valid indicators of body iron status. Red blood cell (RBC) parameters are, however, more easily measured and have also been proposed as indicators of iron depletion. We measured ferritin and TfR in 192 blood donors together with RBC analysis, performed on two haematology analysers. Thirteen donors had parameters suggestive of haemoglobinopathy and were excluded from further analysis. Overall, 10% (18/179) of the remaining donors had iron deficiency, as defined by log(TfR/F) exceeding the 95th percentile of the value in the population of first-time donors. Using receiver operating characteristic analysis, the sensitivity of ferritin was 100%, with a specificity of 90% at a cut-off of 15 mug L(-1). The sensitivity and specificity of RBC-Y at a cut-off of 152 for detecting iron deficiency were 81 and 89%, respectively. Haemoglobin content of reticulocytes, meanwhile, showed sensitivity of 69% and specificity of 93% when a cut-off of 28 pg was used. Both measures compare favourably with haemoglobin which only showed a sensitivity of 50%, although specificity was 91% at a cut-off value of 125 g L(-1). The parameter RBC-Y can be useful as a screening measure for iron deficiency in blood donors.
    No preview · Article · Jul 2008 · Transfusion Medicine
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    G G Gan · J F J Pasagna · G I Eow · V S Nadarajan
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    ABSTRACT: Chronic neutrophilic leukaemia is a rare myeloproliferative disease characterised by splenomegaly, sustained neutrophilia, raised vitamin B12 level and absence of the Philadelphia chromosome. We report a 74-year-old man who presented first with Sweet's syndrome and subsequently leukocytosis. He had splenomegaly, a raised vitamin B12 level, serum uric acid and neutrophil alkaline phosphatase score. Cytogenetic study of the marrow was normal and peripheral blood for BCR-ABL gene transcript was not detectable. He subsequently passed away with bronchopneumonia.
    Full-text · Article · Apr 2007 · Singapore medical journal