MyMedR

Displaying publications 21 - 40 of 41 in total

Abstract:

Sort:

Increased PAC-1 expression among patients with multiple myeloma on concurrent thalidomide and warfarin

Abdullah WZ, Roshan TM, Hussin A, Zain WS, Abdullah D

Blood Coagul Fibrinolysis, 2013 Dec;24(8):893-5.
PMID: 24030118 DOI: 10.1097/MBC.0b013e3283642ee2

Treatment with thalidomide is associated with vascular thrombosis. The effect of thalidomide on platelet activation is unclear, although the use of aspirin is justified for thromboprophylaxis. A study on platelet activation markers was done among multiple myeloma patients receiving thalidomide therapy with warfarin as thromboprophylaxis. Strict criteria and procedure were set to avoid misinterpretation of platelet activation other than due to the thalidomide's effect. Blood specimen pre and post thalidomide therapy were used for flow cytometric analysis. Platelet surface P-selectin, CD62P expression and PAC-1 (antibody that recognizes conformational change of the GPIIb/IIIa complex) were examined by using three-colour flowcytometer. Increased expression marker for PAC-1 was observed after 4 weeks of thalidomide treatment (P
Genetic polymorphisms of HbE/beta thalassemia related to clinical presentation: implications for clinical diversity

Azman NF, Abdullah WZ, Hanafi S, Diana R, Bahar R, Johan MF, et al.

Ann Hematol, 2020 Apr;99(4):729-735.
PMID: 32078010 DOI: 10.1007/s00277-020-03927-5

HbE/Beta thalassemia (HbE/β-thalassemia) is one of the common genetic disorders in South East Asia. It is heterogeneous in its clinical presentation and molecular defects. There are genetic modifiers which have been reported to influence the disease severity of this disorder. The aim of this study was to determine the genetic polymorphisms which were responsible for the disease clinical diversity. A case-control study was conducted among Malay transfusion-dependent HbE/β-thalassemia patients. Patients who were confirmed HbE/β-thalassemia were recruited and genotyping study was performed on these subjects. Ninety-eight patients were selected and divided into moderate and severe groups based on clinical parameters using Sripichai scoring system (based on hemoglobin level, spleen size, growth development, the age of first transfusion and age of disease presentation). Forty-three (44.9%) and 55 (56.1%) patients were found to have moderate and severe clinical presentation, respectively. Genotyping analysis was performed using Affymetrix 6.0 microarray platform. The SNPs were filtered using PLINK and Manhattan plot by R software. From the GWAS results, 20 most significant SNPs were selected based on disease severity when compared between moderate and severe groups. The significant SNPs found in this study were mostly related to thalassemia complications such as rs7372408, associated with KCNMB2-AS1 and SNPs associated with disease severity. These findings could be used as genetic predictors in managing patients with HbE/β-thalassemia and served as platform for future study.
Physicochemical evaluation and in vitro hemocompatibility study on nanoporous hydroxyapatite

Ooi CH, Ling YP, Abdullah WZ, Mustafa AZ, Pung SY, Yeoh FY

J Mater Sci Mater Med, 2019 Mar 30;30(4):44.
PMID: 30929088 DOI: 10.1007/s10856-019-6247-5

Hydroxyapatite is an ideal biomaterial for bone tissue engineering due to its biocompatibility and hemocompatibility which have been widely studied by many researchers. The incorporation of nanoporosity into hydroxyapatite could transform the biomaterial into an effective adsorbent for uremic toxins removal especially in artificial kidney system. However, the effect of nanoporosity incorporation on the hemocompatibility of hydroxyapatite has yet to be answered. In this study, nanoporous hydroxyapatite was synthesized using hydrothermal technique and its hemocompatibility was determined. Non-ionic surfactants were used as soft templates to create porosity in the hydroxyapatite. The presence of pure hydroxyapatite phase in the synthesized samples is validated by X-ray diffraction analysis and Fourier transform infrared spectroscopy. The TEM images show that the hydroxyapatite formed rod-like particles with the length of 21-90 nm and diameter of 11-70 nm. The hydroxyapatite samples exhibit BET surface area of 33-45 m2 g-1 and pore volume of 0.35-0.44 cm3 g-1. The hemocompatibility of the hydroxyapatite was determined via hemolysis test, platelet adhesion, platelet activation and blood clotting time measurement. The nanoporous hydroxyapatite shows less than 5% hemolysis, suggesting that the sample is highly hemocompatible. There is no activation and morphological change observed on the platelets adhered onto the hydroxyapatite. The blood clotting time demonstrates that the blood incubated with the hydroxyapatite did not coagulate. This study summarizes that the synthesized nanoporous hydroxyapatite is a highly hemocompatible biomaterial and could potentially be utilized in biomedical applications.
Fulltext Familial antithrombin III deficiency in a Malay patient with massive thrombosis

Wan Ab Rahman WS, Abdullah WZ, Hassan MN, Hussin A, Zulkafli Z, Haron J

Malays J Pathol, 2017 Aug;39(2):197-200.
PMID: 28866705 MyJurnal

Patients with low antithrombin III (AT III) has increased risk for arteriovenous thromboembolic (TE) disease. We report a 28-year-old Malay lady who presented with spontaneous right calf pain and swelling of one week duration. She was on oral contraceptive pills and had a history of travelling for a long distance prior to the presentation. Her brother who was diagnosed with AT III deficiency had arterial thrombosis at a young age. She was diagnosed as having right popliteal vein thrombosis by ultrasound and treated with subcutaneous fondaparinux. While on treatment, she developed massive bilateral pulmonary embolism (PE). Thrombophilia study showed reduced AT III activity (38μl/dl) and normal results for protein C, protein S, activated protein C resistance and lupus anticoagulant assays. This patient has heterozygous AT III deficiency added with significant acquired factors responsible for the TE events. Those with AT III deficiency may have resistance to heparin therapy and require higher doses of heparin.
Fulltext Extreme Thrombocytosis in a Child: Laboratory Approaches and Diagnostic Challenges

Zulkafli Z, Janaveloo T, Wan Ab Rahman WS, Hassan MN, Abdullah WZ

Oman Med J, 2019 Jul;34(4):336-340.
PMID: 31360323 DOI: 10.5001/omj.2019.65

Thrombocytosis in children as well as in adult is defined as platelet count ≥ 450 × 109/L, and it is usually a reactive feature to various medical disorders. However, extreme thrombocytosis (platelet count ≥ 1000 × 109/L) is an uncommon finding among pediatric and adult patients, which may indicate more than a reactive phenomenon. We describe a case of a five-year-old boy who was admitted due to recurrent epistaxis. He had no history of allergic tendency or trauma. Physical examination was unremarkable except for shotty neck nodes. Laboratory results at presentation showed normal hemoglobin and total leukocyte count with eosinophilia (0.92 × 109/L), and extreme thrombocytosis. Other relevant investigations including coagulation profile, serum ferritin, liver, and renal function tests were all within normal ranges. Stool samples for ova and cysts were negative. The peripheral blood smear and bone marrow aspirate confirmed thrombocytosis with increased megakaryocytic proliferation and no artefactual reasons for the high platelets such as red blood cell fragments. Different causes of thrombocytosis in childhood were investigated after considering the possible differential diagnoses for extreme thrombocytosis.
Fulltext Hemolytic Disease of Fetus and Newborn in a Primigravida with Multiple Alloantibodies Involving Anti-Jka and Anti-E: A Case Report

Iberahim S, Aizuddin MJ, Kadir NA, Rameli N, Adzahar S, Noor NHM, et al.

Oman Med J, 2020 Nov;35(6):e206.
PMID: 33335745 DOI: 10.5001/omj.2020.135

The majority of hemolytic disease of the fetus and newborn (HDFN) reported in the literature is due to ABO and rhesus incompatibility. However, there are also other minor blood groups that have been identified as a cause of HDFN, although the occurrence is much rarer. The antibody screening program for D negative mother and the anti-D immunoglobulin treatment showed a significant reduction of the occurrence of HDFN secondary to anti-D. In a developed country, the screening for red blood cell antibody in the pregnant mother other than anti-D reduced the possibility of HDFN occurrence hence reduced the fetal morbidity and subsequently increased the fetal well being during pregnancy and after the postnatal period. In this case report, we discuss HDFN in a primigravida patient secondary to multiple alloantibodies (anti-Jka and anti-E). The baby developed jaundice with bilirubin levels approaching the exchange transfusion level. However, with extensive phototherapy and immunoglobulin treatment, the child did not require exchange transfusion. We also included the importance of the routine antenatal antibody screening program. This practice will help the transfusion center to find the antigen negative blood in a timely manner and reduce the morbidities and mortalities of HDFN among the newborns.
Fulltext Performance Comparison Between Conventional Fluorescent Spot Test and Quantitative Assay in Detecting G6PD Deficiency in Neonates

Halim SA, Bahar R, Abdullah WZ, Zon EM, Yusoff SM

Oman Med J, 2023 Jul;38(4):e524.
PMID: 37724319 DOI: 10.5001/omj.2023.86

OBJECTIVES: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzymopathy worldwide. The fluorescent spot test (FST) is the conventional method for screening neonates for G6PD. However, it has limitations and quantitative assays such as the CareStart Biosensor 1 are being increasingly recommended. This study aimed to compare FST and CareStart Bioensor 1 in their ability to detect G6PD levels in neonates.
METHODS: This cross-sectional study involved 455 neonates between June and December 2020. Two milliliters of cord blood were analyzed with CareStart Biosensor 1 and dried cord blood spots with FST. Data was recorded and statistically analyzed. Sensitivity, specificity, positive predictive value, and negative predictive value were calculated to determine the performance of FST at specific G6PD cut-off values; Cohen's kappa analysis assessed the agreement between the two methods.
RESULTS: The sensitivity of FST at 30% cut-off G6PD activity level was 91.0%, (95% CI: 57.0-100) and specificity of 97.0% (95% CI: 95.0-98.0). At 60% cut-off, the FST sensitivity sharply declined to 29.0% (95% CI: 19.0-40.0) with a specificity of 100% (95% CI: 98.0-100). The overall prevalence of G6PD deficiency was 5.1% as measured by FST and 17.8% by Biosensor 1 (p < 0.001).
CONCLUSIONS: In this study, FST missed a significant proportion of cases of intermediate G6PD levels. FST also misclassified several G6PD intermediate individuals as normal, rendering them susceptible to oxidative stress. Biosensor 1 reported a significantly higher prevalence of G6PD deficiency.
Molecular heterogeneity of glucose-6-phosphate dehydrogenase deficiency in Malays in Malaysia

Yusoff NM, Shirakawa T, Nishiyama K, Ghazali S, Ee CK, Orita A, et al.

Int J Hematol, 2002 Aug;76(2):149-52.
PMID: 12215013 DOI: 10.1007/BF02982577

Multiplex polymerase chain reaction (PCR) using multiple tandem forward primers and a common reverse primer (MPTP) was recently established as a comprehensive screening method for mutations in X-linked recessive diseases. In the work reported here, MPTP was used to scan for mutations of the glucose-6-phosphate dehydrogenase (G6PD) gene. Mutations in exons 3,4,5,6,7,9, 11, and 12 of the G6PD gene were screened by MPTP in 93 unrelated Malaysian patients with G6PD deficiency. Of the 93 patients, 80 (86%) had identified mutations. Although all of these were missense mutations, identified nucleotide changes were heterogeneous, with 9 mutations involving various parts of the exons. These 9 mutations were G-to-A nucleotide changes at nucleotide 871 of the G6PD gene (G871A), corresponding to G6PD Viangchan, G6PD Mediterranean (C563T), G6PD Vanua Lava (T383C), G6PD Coimbra (C592T), G6PD Kaiping (G1388A), G6PD Orissa (C131G), G6PD Mahidol (G487A), G6PD Canton (G1376T), and G6PD Chatham (G1003A). Our results document heterogeneous mutations of the G6PD gene in the Malaysian population.
The absence of factor V Leiden mutation in Malays with recurrent spontaneous abortions

Yusoff NM, Abdullah WZ, Ghazali S, Othman MS, Baba AA, Abdullah N, et al.

Aust N Z J Obstet Gynaecol, 2002 May;42(2):164-6.
PMID: 12069143 DOI: 10.1111/j.0004-8666.2002.00164.x

OBJECTIVES: The objectives of this study were to investigate the prevalence of factor V Leiden mutation in Malay women with recurrent spontaneous abortion and to clarify the contribution of the factor V Leiden mutation to recurrent miscarriages in these women.

DESIGN: A prospective case control study between June 1999 and April 2000.

SETTING: Hospital University Science of Malaysia, Kubang Kerian, Kelantan, and Maternal and Child Health Clinic, Pasir Mas, Kelantan, Malaysia.

SAMPLES: A total of 46 Malay women with a history of three or more first or second trimester miscarriages were studied. The control group consisted of 46 parous women without obstetric complications.

METHODS: Diagnosis of factor V Leiden mutation was made by examination of factor V Leiden allele product following Mnl I digestion of factor V Leiden alleles amplified by polymerase chain reaction.

RESULTS: None of the 46 women with recurrent spontaneous abortion carried the mutation. Also, we found no subject carrying the factor V Leiden alleles in the control group.

CONCLUSION: These results suggest that that there is no association between the factor V Leiden mutation and recurrent spontaneous abortion in the Malay population.
Kenaf (Hibiscus cannabinus L.) Seed and its Potential Food Applications: A Review

Giwa Ibrahim S, Karim R, Saari N, Wan Abdullah WZ, Zawawi N, Ab Razak AF, et al.

J Food Sci, 2019 Aug;84(8):2015-2023.
PMID: 31364175 DOI: 10.1111/1750-3841.14714

Kenaf belongs to the family Malvaceae noted for their economic and horticultural importance. Kenaf seed is a valuable component of kenaf plant. For several years, it has been primarily used as a cordage crop and secondarily as a livestock feed. The potential for using kenaf seeds as a source of food-based products has not been fully exploited. Consumers are becoming more interested in naturally healthy plant-based food products. Kenaf seed, the future crop with a rich source of essential nutrients and an excellent source of phytocompounds, might serve suitable roles in the production of value-added plant-based foods. At present kenaf seed and its value-added components have not been effectively utilized for both their nutritional and functional properties as either ingredient or major constituent of food products. This review focuses on the possible food applications of kenaf seed and its value-added components based on their nutritional composition and functional properties available in literature, with the purpose of providing an overview on the possible food applications of this underutilized seed. The review focuses on a brief introduction on kenaf plant, nutritional function, lipids and proteins composition and food applications of the seed. The review elaborately discusses the seed in terms of; bioactive components, antioxidants enrichment of wheat bread, antimicrobial agents, as edible flour, as edible oil and a source of protein in food system. The review closes with discussion on other possible food applications of kenaf seed. The need for food scientists and technologists to exploit this natural agricultural product as a value-added food ingredient is of great significance and is emphasized.
Sagittal sinus thrombosis in a patient with familial Protein C deficiency: Highlighting the impact of thrombophilia testing

Wan Ab Rahman WS, Abdullah WZ, Hassan MN, Ahmed S, Zulkafli Z, Wan Ahmed WA, et al.

Malays J Pathol, 2021 Dec;43(3):449-452.
PMID: 34958066

Plasma protein-C is a natural anticoagulant that inactivates factors Va and VIIIa. Familial protein C deficiency is inherited as an autosomal dominant disorder. The homozygous or compound heterozygous type may present early as purpura fulminant, while the heterozygous type can present as thromboembolism later in life. Presented in this report is a case of a 21-year-old female patient with protein-C deficiency, confirmed by thrombophilia investigations. She experienced recurrent deep vein thrombosis and cerebral sinus thrombosis due to thrombotic occlusion. She had a family history of deep vein thrombosis. Hence, high-risk cases should be seriously considered for long term anticoagulation therapy. The utility versus futility of thrombophilia testing in a particular situation is discussed to address and ensure safe practice among patients with thromboembolism.
Fulltext Elevated Circulating Microparticle Subpopulations in Incidental Cerebral White Matter Hyperintensities: A Multimodal Study

Nassir CMNCM, Ghazali MM, Safri AA, Jaffer U, Abdullah WZ, Idris NS, et al.

Brain Sci, 2021 Jan 20;11(2).
PMID: 33498429 DOI: 10.3390/brainsci11020133

Asymptomatic (or "silent") manifestations of cerebral small vessel disease (CSVD) are widely recognized through incidental findings of white matter hyperintensities (WMHs) as a result of magnetic resonance imaging (MRI). This study aims to examine the potential associations of surrogate markers for the evaluation of white matter integrity in CSVD among asymptomatic individuals through a battery of profiling involving QRISK2 cardiocerebrovascular risk prediction, neuroimaging, neurocognitive evaluation, and microparticles (MPs) titers. Sixty asymptomatic subjects (mean age: 39.83 ± 11.50 years) with low to moderate QRISK2 scores were recruited and underwent neurocognitive evaluation for memory and cognitive performance, peripheral venous blood collection for enumeration of selected MPs subpopulations, and 3T MRI brain scan with specific diffusion MRI (dMRI) sequences inclusive of diffusion tensor imaging (DTI). WMHs were detected in 20 subjects (33%). Older subjects (mean age: 46.00 ± 12.00 years) had higher WMHs prevalence, associated with higher QRISK2 score and reduced processing speed. They also had significantly higher mean percentage of platelet (CD62P)- and leukocyte (CD62L)-derived MPs. No association was found between reduced white matter integrity-especially at the left superior longitudinal fasciculus (LSLF)-with age and neurocognitive function; however, LSLF was associated with higher QRISK2 score, total MPs, and CD62L- and endothelial cell-derived MPs (CD146). Therefore, this study establishes these multimodal associations as potential surrogate markers for "silent" CSVD manifestations in the well-characterized cardiocerebrovascular demographic of relatively young, neurologically asymptomatic adults. Furthermore, to the best of our knowledge, this study is the first to exhibit elevated MP counts in asymptomatic CSVD (i.e., CD62P and CD62L), which warrants further delineation.
Platelet Additive Solutions as an Alternative Storage Medium of Apheresis Platelets to Reduce ABO Antibody Titer for ABO-Incompatibility Platelet Transfusion

Adzahar S, Hassan MN, Zulkafli Z, Mohd Noor NH, Ramli M, Mohamed Yusoff S, et al.

Cureus, 2023 Aug;15(8):e44012.
PMID: 37746385 DOI: 10.7759/cureus.44012

Introduction Platelet additive solutions (PASs) are nutrient media commonly used to replace and reduce the need for storage plasma. They are an alternative medium to maintain high-quality platelets lasting longer on the shelf for about seven days. Platelets with high titer of ABO antibody can pose a hemolytic transfusion reaction (HTR) risk if units are given across the ABO barrier. The risk of complication is greater when group O platelet is released to non-group O patients. The PAS has been known as a safe medium, where the titer of ABO antibodies is expected to be diluted. In this study, we compared the anti-A and anti-B antibody titers of apheresis platelets in PAS and non-PAS (plasma) as the suspending media. Methods A total of 20 apheresis platelet donors were selected, with seven from blood group A, eight from blood group B, and five from blood group O. The platelets were collected using an Amicus cell separator. They were suspended in PAS and plasma before being stored at a temperature range of 22-24º C. Anti-A (blood group B and O) and Anti-B (blood group A and O) antibody titers were measured and compared between the two suspending media. Wilcoxon signed-rank test is used for statistical analysis, and a p-value <0.05 is considered significant. Results The median titer of the anti-A antibody of apheresis platelets showed a significant difference between suspended in PAS (2.50) and plasma (4.00), p=0.002. Similar findings were also seen with the median titer of the anti-B antibody of apheresis platelet, in which it showed a significant difference between suspended in PAS (2.00) and plasma (4.00), p=0.004. It was observed that there was a significant reduction in both anti-A and anti-B antibody titers in the PAS as compared to the plasma group. Conclusion The decrease in ABO antibody titer in apheresis platelets stored with PAS can be beneficial for patients. This reduces the risk of HTRs if ABO-incompatible platelet units need to be issued. Thus, using PAS as a storage medium significantly improves platelet inventory management without compromising patient safety.
Fulltext Anti-tumor activity of Eurycoma longifolia root extracts against K-562 cell line: in vitro and in vivo study

Al-Salahi OS, Ji D, Majid AM, Kit-Lam C, Abdullah WZ, Zaki A, et al.

PLoS One, 2014;9(1):e83818.
PMID: 24409284 DOI: 10.1371/journal.pone.0083818

Eurycoma longifolia Jack has been widely used in traditional medicine for its antimalarial, aphrodisiac, anti-diabetic, antimicrobial and anti-pyretic activities. Its anticancer activity has also been recently reported on different solid tumors, however no anti-leukemic activity of this plant has been reported. Thus the present study assesses the in vitro and in vivo anti-proliferative and apoptotic potentials of E. longifolia on K-562 leukemic cell line. The K-562 cells (purchased from ATCC) were isolated from patients with chronic myelocytic leukemia (CML) were treated with the various fractions (TAF273, F3 and F4) of E. longifolia root methanolic extract at various concentrations and time intervals and the anti-proliferative activity assessed by MTS assay. Flow cytometry was used to assess the apoptosis and cell cycle arrest. Nude mice injected subcutaneously with 10(7) K-562 cells were used to study the anti-leukemic activity of TAF273 in vivo. TAF273, F3 and F4 showed various degrees of growth inhibition with IC50 values of 19, 55 and 62 µg/ml, respectively. TAF273 induced apoptosis in a dose and time dependent manner. TAF273 arrested cell cycle at G1 and S phases. Intraperitoneal administration of TAF273 (50 mg/kg) resulted in a significant growth inhibition of subcutaneous tumor in TAF273-treated mice compared with the control mice (P = 0.024). TAF273 shows potent anti-proliferative activity in vitro and in vivo models of CML and therefore, justifies further efforts to define more clearly the potential benefits of using TAF273 as a novel therapeutic strategy for CML management.
Intracerebral haematomas after deep brain stimulation surgery in a patient with Tourette syndrome and low factor XIIIA activity

Idris Z, Ghani AR, Mar W, Bhaskar S, Wan Hassan WN, Tharakan J, et al.

J Clin Neurosci, 2010 Oct;17(10):1343-4.
PMID: 20620064 DOI: 10.1016/j.jocn.2010.01.054

A 24-year-old male patient with refractory Tourette syndrome was treated with deep brain stimulation (DBS) and developed subsequent bilateral subcortical haematomas. Additional blood tests revealed abnormalities of plasma factor XIIIA and tryptophan levels, which may be associated with Tourette syndrome. Neurosurgeons who perform DBS surgery on patients with Tourette syndrome must be aware of possible disastrous complications resulting from factor XIIIA disorders of blood haemostasis. Routine screening for this condition is not typically performed prior to surgery in these patients.
Anti-angiogenic quassinoid-rich fraction from Eurycoma longifolia modulates endothelial cell function

Al-Salahi OS, Kit-Lam C, Majid AM, Al-Suede FS, Mohammed Saghir SA, Abdullah WZ, et al.

Microvasc Res, 2013 Nov;90:30-9.
PMID: 23899415 DOI: 10.1016/j.mvr.2013.07.007

Targeting angiogenesis could be an excellent strategy to combat angiogenesis-dependent pathophysiological conditions such as cancer, rheumatoid arthritis, obesity, systemic lupus erythematosus, psoriasis, proliferative retinopathy and atherosclerosis. Recently a number of clinical investigations are being undertaken to assess the potential therapeutic application of various anti-angiogenic agents. Many of these angiogenesis inhibitors are directed against the functions of endothelial cells, which are considered as the building blocks of blood vessels. Similarly, roots of a traditional medicinal plant, Eurycoma longifolia, can be used as an alternative treatment to prevent and treat the angiogenesis-related diseases. In the present study, antiangiogenic potential of partially purified quassinoid-rich fraction (TAF273) of E. longifolia root extract was evaluated using ex vivo and in vivo angiogenesis models and the anti-angiogenic efficacy of TAF273 was investigated in human umbilical vein endothelial cells (HUVEC). TAF273 caused significant suppression in sprouting of microvessels in rat aorta with IC50 11.5μg/ml. TAF273 (50μg/ml) showed remarkable inhibition (63.13%) of neovascularization in chorioallantoic membrane of chick embryo. Tumor histology also revealed marked reduction in extent of vascularization. In vitro, TAF273 significantly inhibited the major angiogenesis steps such as proliferation, migration and differentiation of HUVECs. Phytochemical analysis revealed high content of quassinoids in TAF273. Specially, HPLC characterization showed that TAF273 is enriched with eurycomanone, 13α(21)-epoxyeurycomanone and eurycomanol. These results demonstrated that the antiangiogenic activity of TAF273 may be due to its inhibitory effect on endothelial cell proliferation, differentiation and migration which could be attributed to the high content of quassinoids in E. longifolia.
Elevated annexin A5 plasma levels in term pregnancies of M2/ANXA5 carriers

Ang KC, Kathirgamanathan S, Ch'ng ES, Abdullah WZ, Yusoff NM, Jahnke CM, et al.

Thromb Res, 2017 08;156:87-90.
PMID: 28605660 DOI: 10.1016/j.thromres.2017.06.008
Fulltext Genotype-phenotype association of Hbe/β thalassemia disease and the role of genetic modifiers

HanafI S, Abdullah WZ, Adnan RA, Bahar R, Johan MF, Azman NF, et al.

Malaysian Journal of Paediatrics and Child Health, 2016;22(1):1-16.
MyJurnal

HbE/β-thalassemia is the most common severe form of thalassemia particularly in SEA region including Malaysia and globally, it comprised of a significant severe form of β-thalassemia disorder. It has various clinical manifestations ranging from very mild anemia to severe manifestation similar to beta thalassemia major. Many different syndromes are observed in HbE/β-thalassemia. Several genetic modifiers have been reported to play important role in contributing to phenotypic variability. The true reasons underlying this phenotypic variability remain unknown. The most reliable predictive factor of the disease phenotype is the nature of the beta globin gene mutation itself. However, the degree of severity is also believed to be affected by other genetic modifiers. For instance, high HbF level ameliorates the clinical severity of β thalassemia patients. Therefore, identification of these genetic modifiers is very important. The association of severe clinical manifestation and the specific β-globin gene mutation has been known. But the wide scope and other potential predictors have been only recently appreciated. This review therefore aimed to reveal the potential genetic modifiers of HbE/βthalassemia patients based on the previous reported studies. A better understanding on the mechanisms underlying the variety of phenotypes of this disease may lead to the direction for a better future management plans. This also promotes “personalized medicine” in patient care.
Fulltext Genetic analysis of the M2/ANXA5 haplotype as recurrent pregnancy loss predisposition in the Malay population

Ang KC, Kathirgamanathan S, Ch'ng ES, Lee YY, Roslani AL, Naidu B, et al.

J Assist Reprod Genet, 2017 Apr;34(4):517-524.
PMID: 28108842 DOI: 10.1007/s10815-017-0871-0

PURPOSE: The aim of this study was to evaluate a new predisposition factor, M2/ANXA5 (RPRGL3), in recurrent pregnancy loss (RPL) patients of Malay origin, since it was previously known that the prevalence of this condition is relatively high among the Malay population of Malaysia, where conventional hereditary thrombophilia factors have been generally ruled out.
METHODS: A total of 232 women who had experienced ≥2 unexplained RPL and 141 available male partners were recruited, with 360 healthy Malay and 166 parous female controls. Prevalence of M2 carriage and RPL odds ratios were calculated in (a) control and patient groups; (b) clinically defined subgroups in categories of pregnancy loss, primary, secondary, and tertiary; and (c) timing of pregnancy loss in early, ≤15th gestation week and "late" fetal losses, and >15th gestation week subgroups.
RESULTS: Both male and female subjects had similar M2/ANXA5 allele frequencies. The carrier rate of M2/ANXA5 for the general Malay population was 42.2 and 34.9% for parous controls. These carrier rates compared to Malay RPL subjects (52% M2 carriers) resulted in elevated odds ratios (95% confidence interval) of 1.53 (1.1 to 2.1) and 1.97 (1.3 to 3.1) accordingly for early fetal losses. Moreover, exceeding copy numbers of M2/ANXA5 alleles seemed to afflict a greater chance of RPL in couples, especially when both partners were M2 carriers.
CONCLUSION: This study confirmed the proposed role of M2/ANXA5 as embryonic, genetically associated thrombophilia predisposition factor for early RPL among ethnic Malay of Malaysia.
Fulltext Multiplex amplification refractory mutation system (MARMS) for the detection of β-globin gene mutations among the transfusion-dependent β-thalassemia Malay patients in Kelantan, Northeast of Peninsular Malaysia

Hanafi S, Hassan R, Bahar R, Abdullah WZ, Johan MF, Rashid ND, et al.

Am J Blood Res, 2014;4(1):33-40.
PMID: 25232503

The aim of this study was to adapt MARMS with some modifications to detect beta mutation in our cohort of thalassemia patients. We focused only on transfusion-dependent thalassemia Malay patients, the predominant ethnic group (95%) in the Kelantanese population. Eight mutations were identified in 46 out of 48 (95.83%) beta thalassemia alleles. Most of the patients (54.2%) were compound heterozygous with co-inheritance Cd 26 (G>A). The frequencies of spectrum beta chain mutation among these patients are presented in Table 2. Among the transfusion dependent beta thalassemia Malay patients studied, 26 patients were found to be compound heterozygous and the main alleles were Cd 26 (G>A). Compound heterozygous mutation of Cd 26 (G>A) and IVS 1-5 (G>C) were 12 (46.2%), Cd 26 (G>A) and Cd 41/42 (TTCT) were 9 (34.6%), Cd 26 (G>A) and IVS 1-1 (G>C) were 2 (7.7%) respectively. Meanwhile the minority were made of a single compound heterozygous of Cd 26 (G>A) and Cd 71/72, Cd 26 (>A) and Cd 17 (A>T), Cd 26 (G>A) and -28 (G>A) respectively. Twenty out of forty six patients were shown to have homozygous of IVS 1-5 (G>C) were 2 (10.0%), Cd 26 (G>A) were 15 (75.0%), Cd 19 (A>G) were 1 (5.0%), and IVS 1-1 (G>T) were 2 (10.0%). The beta chain mutations among the Kelantanese Malays followed closely the distribution of beta chain mutations among the Thais and the Malays of the Southern Thailand. The G-C transition at position 5 of the IVS 1-5 mutation was predominant among the Malay patients. In conclusion, this method has successfully identified the mutation spectrum in our cohort of transfusion-dependent beta thalassemia patients, and this method is equally effective in screening for mutation among thalassemia patients.

Filters

Please provide feedback to Administrator (afdal@afpm.org.my)

External Links