Displaying publications 1 - 20 of 21 in total

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  1. Nadarajan VS
    Transfusion, 2018 05;58(5):1189-1198.
    PMID: 29441590 DOI: 10.1111/trf.14538
    BACKGROUND: Antibodies to Mia , MUT, and Mur are among the most frequently identified alloantibodies in Southeast Asia. Understanding the characteristics of these antibodies in terms of induction and evanescence would aid in optimizing methods for their detection.

    STUDY DESIGN AND METHODS: Antibody testing results between the years 2013 and 2015 with relevant patient demographic data and red blood cell (RBC) transfusion history were retrieved. Cumulative alloimmunization incidence and evanescence to MUT and Mur were estimated by Kaplan-Meier analysis in relation to the number of RBC units transfused and time.

    RESULTS: Of 70,543 selected patients, 6186 nonalloimmunized subjects with available antibody testing results posttransfusion were identified. Cumulative alloimmunization incidence for MUT increased from 0.12% (95% confidence interval [CI], 0.03-0.21) to 0.63% (95% CI, 0.25-1.01), while for Mur it increased from 0.04% (95% CI, 0-0.09) to 0.42% (95% CI, 0.05-0.79) when a patient was transfused 2 RBC units as compared to 12. Both antibodies had high evanescence rates and at 1 year, anti-MUT and -Mur will be detected in only 45% (95% CI, 35%-57%) and 27% (95% CI, 17%-43%), respectively, of previously positive patients. MUT and Mur immunogenicity was estimated to be 1.7 and 1.2 times higher than E when their rate of evanescence was taken into account.

    CONCLUSION: Antibodies to MUT and Mur develop following multiple RBC exposures. Immunogenicity of MUT/Mur and evanescence rates of the corresponding antibodies is higher compared to anti-E. Appropriate selection of antibody screening cells is needed in view of the high prevalence, immunogenicity, and evanescence of the antibodies.

  2. Cheong, CS, Gan, GG, Chen, TM, Lim, CC, Nadarajan, VS, Bee, PC
    JUMMEC, 2016;19(2):12-16.
    MyJurnal
    Haemophagocytic lymphohistiocytosis (HLH) is a clinico-pathologic entity caused by increased proliferation
    and activation of benign macrophages with haemophagocytosis throughout the reticulo-endothelial system.
    Virus-associated HLH is a well-recognised entity. Although majority of parvovirus B19 associated HLH does not
    require any specific treatment and carries good prognosis, outcome of children is worse than adults. We report
    here a case of HLH associated with acute parvovirus B19 infection in a young healthy patient with underlying
    hereditary spherocytosis, with bone marrow findings typical of parvovirus infection. Although this patient
    had spontaneous recovery of cell counts, he succumbed due to complication from prolonged ventilation.
    Unexpectedly, his immunoglobulin levels were inappropriately normal despite on-going ventilator associated
    pneumonia, which reflects inadequate humoral immune response towards infection.
  3. Nadarajan VS, Sthaneshwar P, Jayaranee S
    Int J Lab Hematol, 2010 Apr;32(2):215-21.
    PMID: 19566741 DOI: 10.1111/j.1751-553X.2009.01174.x
    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.
  4. Nadarajan VS, Eow GI
    Malays J Pathol, 2002 Dec;24(2):99-102.
    PMID: 12887168
    Iron deficiency is a major complication of regular blood donation as a result of regular iron loss from each donated blood unit. Ninety-two regular blood donors and 95 first time blood donors attending a hospital-based blood transfusion centre were assessed as to their haematological and iron status by blood counts and serum ferritin levels as an indicator of iron stores. All donors had passed the haemoglobin-screening test using a copper sulphate method prior to blood donation. Ferritin levels were found to be significantly lower among regular blood donors (47.8 mmol/L) as compared to first time blood donors (94.2 mmol/L). Iron deficiency as observed by low ferritin levels was seen in 7.4% of all first time donors as compared to 17.4% in regular donors. Male first time donors showed a low prevalence of iron deficiency but the prevalence significantly increased with regular blood donation. Female first time and regular blood donors however did not show any significant differences in prevalence of iron deficiency, with both groups exhibiting prevalence rates similar to male regular donors. The association between haemoglobin levels and iron deficiency was poor and the copper sulphate-screening test was found insensitive to anaemia with many donors passing the test and donating blood despite being anaemic. It is concluded that a high prevalence of iron deficiency is present among regular male blood donors and all female donors. Besides, the use of the copper sulphate screening test as a sole criterion for anaemia screening should be reviewed. Ferritin measurements should be included in the routine assessment of blood donors especially among regular blood donors.
  5. Nadarajan VS, Ang CH, Bee PC
    Eur. J. Haematol., 2012 Feb;88(2):175-8.
    PMID: 21950422 DOI: 10.1111/j.1600-0609.2011.01712.x
    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.
  6. Shanmugam H, Eow GI, Nadarajan VS
    Malays J Pathol, 2009 Jun;31(1):63-6.
    PMID: 19694316 MyJurnal
    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.
  7. Tan JY, Lian LH, Nadarajan VS
    Blood Transfus, 2012 Jul;10(3):368-76.
    PMID: 22682339 DOI: 10.2450/2012.0095-11
    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.
  8. Gan GG, Subramaniam R, Lian LH, Nadarajan V
    Balkan J. Med. Genet., 2013 Dec;16(2):53-8.
    PMID: 24778564 DOI: 10.2478/bjmg-2013-0032
    Interleukin-6 (IL-6) is one of the cytokines that has been well studied and implicated in many diseases including cancers. The frequency of the IL-6 -174 (G/C) polymorphism had been proven to differ in various populations. Malaysia is a country with three major ethnic populations, Malays, Chinese and Indians. In this study, we proposed to determine the G or C allele frequency of the IL-6 -174 polymorphism in these three populations. A total of 348 blood samples were available for analysis. The median age for the subjects was 31 years. There were a total of 245 males and 103 females. A total of 86 Malays (25.0%), 122 Chinese (33.0%) and 140 Indians (40.0%) were genotyped. The result showed a significant difference in the G or C allele frequency of the -174 polymorphism. The total frequencies for the G and C alleles were 91.0 and 9.0%, respectively. In the Malays, the allele frequency of the C allele was 4.0% compared with 19.0% in the Indians. The C allele was not detected in the Chinese population. This finding is the first reported on the Malaysian population and may be important in determining risk of diseases associated with the IL-6 polymorphism in these three populations.
  9. Nadarajan VS, Laing AA, Saad SM, Usin M
    Vox Sang, 2012 Jan;102(1):65-71.
    PMID: 21592136 DOI: 10.1111/j.1423-0410.2011.01507.x
    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.
  10. Bee PC, Gan GG, Nadarajan VS, Latiff NA, Menaka N
    Int J Hematol, 2010 Jan;91(1):136-9.
    PMID: 20047097 DOI: 10.1007/s12185-009-0471-6
    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.
  11. Nadarajan VS, Ooi CH, Sthaneshwar P, Thompson MW
    Int J Lab Hematol, 2010 Feb;32(1 Pt 2):82-7.
    PMID: 19170774 DOI: 10.1111/j.1751-553X.2008.01132.x
    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.
  12. Cheng JY, Samudram H, Lee Lai Ling C, Nadarajan VS
    Transfus Med, 2022 Dec;32(6):484-491.
    PMID: 36239101 DOI: 10.1111/tme.12924
    OBJECTIVES: To evaluate the performance and utility of a time-temperature indicator (TTI) to determine the cumulative exposure time (CET) of red cell components (RCC) to temperatures above 10°C occurring within and outside the transfusion laboratory.

    BACKGROUND AND OBJECTIVES: Blood centres often use the '30 or 60-min rule' for accepting RCC exposed to room temperature (RT) back into inventory. Effective monitoring of these temperature deviations is however lacking.

    MATERIALS AND METHODS: A Timestrip PLUS® TP153 10°C (TS + 10) TTI was attached to RCC units after preparation of the unit in the blood bank or on issue to the ward, to track the CET > 10°C during laboratory processing and outside the transfusion laboratory.

    RESULTS: The mean CET of 153 RCC tracked within the laboratory was 56 min. Sixty-four (41.8%) and 34 (22.2%) of RCC had core temperature (CT) >10°C for more than 30 and 60 min, respectively. Among the 69 RCC that were returned unused, 27 (39.1%), 17 (24.6%) and 5 (7.2%) RCC units had CT >10°C for more than 30, 60 and 120 min respectively.

    CONCLUSION: A large proportion of RCC have CT >10°C exceeding 30 min during handling within the transfusion laboratory, as well as when RCC are returned unused from transfusion locations. Corrective measures should be implemented to better manage the cold chain to avoid undesirable consequences to blood transfusion. A temperature sensitive device that can also indicate CET can be employed to objectively monitor the period that RCC remained at a CT that exceeds 10°C.

  13. Gan GG, Pasagna JF, Eow GI, Nadarajan VS
    Singapore Med J, 2007 Mar;48(3):e74-6.
    PMID: 17342275
    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.
  14. Gan GG, Leong YC, Bee PC, Chin EF, Abdul Halim H, Nadarajan VS, et al.
    Cytokine, 2016 Feb;78:55-61.
    PMID: 26638029 DOI: 10.1016/j.cyto.2015.11.022
    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.
  15. Nadarajan VS, Phan CL, Ang CH, Liang KL, Gan GG, Bee PC, et al.
    Int J Hematol, 2011 Apr;93(4):465-473.
    PMID: 21387093 DOI: 10.1007/s12185-011-0796-9
    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.
  16. Lau JZH, Chua CL, Chan YF, Nadarajan VS, Lee CLL, Sam IC
    J Gen Virol, 2023 Apr;104(4).
    PMID: 37043371 DOI: 10.1099/jgv.0.001842
    Chikungunya virus (CHIKV) is a re-emerging mosquito-borne virus, which causes epidemics of fever, joint pain and rash. There are three genotypes: West African, East/Central/South/Africa (ECSA) and Asian, with the latter two predominant globally. Genotype-specific differences in clinical presentations, virulence and immunopathology have been described. Macrophages are key cells in immune responses against CHIKV. Circulating blood monocytes enter tissue to differentiate into monocyte-derived macrophages (MDMs) in response to CHIKV infection at key replication sites such as lymphoid organs and joints. This study analyses differences in replication and induced immune mediators following infection of MDMs with Asian and ECSA CHIKV genotypes. Primary human MDMs were derived from residual blood donations. Replication of Asian (MY/06/37348) or ECSA (MY/08/065) genotype strains of CHIKV in MDMs was measured by plaque assay. Nineteen immune mediators were measured in infected cell supernatants using multiplexed immunoassay or ELISA. MY/08/065 showed significantly higher viral replication at 24 h post-infection (h p.i.) but induced significantly lower expression of proinflammatory cytokines (CCL-2, CCL-3, CCL-4, RANTES and CXCL-10) and the anti-inflammatory IL-1Ra compared to MY/06/37348. No differences were seen at later time points up to 72 h p.i. During early infection, MY/08/065 induced lower proinflammatory immune responses in MDMs. In vivo, this may lead to poorer initial control of viral infection, facilitating CHIKV replication and dissemination to other sites such as joints. This may explain the consistent past findings that the ECSA genotype is associated with greater viremia and severity of symptoms than the Asian genotype. Knowledge of CHIKV genotype-specific immunopathogenic mechanisms in human MDMs is important in understanding of clinical epidemiology, biomarkers and therapeutics in areas with co-circulation of different genotypes.
  17. Kyaw TZ, Maniam JA, Bee PC, Chin EF, Nadarajan VS, Shanmugam H, et al.
    Turk J Haematol, 2012 Sep;29(3):278-82.
    PMID: 24744674 DOI: 10.5505/tjh.2012.94809
    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.
  18. Takeshita A, Watanabe H, Yamada C, Nadarajan VS, Permpikul P, Sinkitjasub A, et al.
    Transfus Apher Sci, 2020 Oct;59(5):102944.
    PMID: 33228922 DOI: 10.1016/j.transci.2020.102944
    As an East-Asian international study, we evaluated erythrocyte alloimmunity by gender and history of transfusion or pregnancy. In total, data from more than 1,826,000 patients were analyzed, from whom 26,170 irregular erythrocyte antibodies were detected in 22,653 cases. Antibody frequencies in these cases were as follows: anti-E, 26.8%; anti-Lea, 20.0%; anti-P1, 7.1%; anti-M, 6.4%; anti-Mia, 5.6%; anti-c + E, 5.6%; anti-Leb, 4.6%; anti-D, 2.8%; anti-Fyb, 2.6%; anti-Lea+Leb, 2.5%; anti-Dia, 2.0%; and others. For pregnant patients, anti-D (12.7%) was statistically more frequent. For transfused patients, anti-E (37.3%), anti-c + E (9.5%), anti-C + e (3.3%) and anti-Jka (3.1%) were significantly more frequent.
  19. Fung YL, Alcantara RM, Cavalli LB, Chen JW, Chen YY, Donkin R, et al.
    Vox Sang, 2023 Sep 27.
    PMID: 37753662 DOI: 10.1111/vox.13530
    BACKGROUND AND OBJECTIVES: Securing an adequate blood supply relies on accurate knowledge of blood donors and donation practices. As published evidence on Asian populations is sparse, this study aims to gather up-to-date information on blood donors and donation practices in Asia to assist planning and strategy development.

    MATERIALS AND METHODS: Ten blood collection agencies (BCAs) provided 12 months' data on donors who met eligibility criteria or were deferred, as well as details of their donation practices. Body mass index and blood volumes were calculated and analysed.

    RESULTS: Data on 9,599,613 donations and 154,834 deferrals from six national and four regional BCAs revealed varied donation eligibility and collection practices. Seven used haemoglobin (Hb) criteria below the World Health Organization anaemia threshold. Seven accepted donors weighing <50 kg. Data collection on the weight and height of donors and on deferrals was inconsistent, often not routine. Deferred donors appear to weigh less, with corresponding lower estimated blood volume.

    CONCLUSION: The diversity in eligibility criteria and donation practices reflects each BCA's strategy for balancing donor health with securing an adequate blood supply. Use of lower Hb criteria substantiate their appropriateness in Asia and indicate the need to define Hb reference intervals relevant to each population. We encourage routine gathering of donor weight and height data to enable blood volume estimation and local optimization of donation volumes. Blood volume estimation formulae specific for the Asian phenotype is needed. Information from this study would be useful for tailoring donation criteria of Asian donors around the world.

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