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Domestic and imported products--the Malaysian experience in assuring safe and sufficient plasma products

Ayob Y

Dev Biol (Basel), 2007;127:169-73.
PMID: 17486890
Hemovigilance in developing countries

Ayob Y

Biologicals, 2010 Jan;38(1):91-6.
PMID: 20133151 DOI: 10.1016/j.biologicals.2009.10.002

Hemovigilance like quality systems and audits has become an integral part of the Blood Transfusion Service (BTS) in the developed world and has contributed greatly to the development of the blood service. However developing countries are still grappling with donor recruitment and efforts towards sufficiency and safety of the blood supply. In these countries the BTS is generally fragmented and a national hemovigilance program would be difficult to implement. However a few developing countries have an effective and sustainable blood program that can deliver equitable, safe and sufficient blood supply to the nation. Different models of hemovigilance program have been introduced with variable success. There are deficiencies but the data collected provided important information that can be presented to the health authorities for effective interventions. Hemovigilance program modeled from developed countries require expertise and resources that are not available in many developing countries. Whatever resources that are available should be utilized to correct deficiencies that are already apparent and obvious. Besides there are other tools that can be used to monitor the blood program in the developing countries depending on the need and the resources available. More importantly the data collected should be accurate and are used and taken into consideration in formulating guidelines, standards and policies and to affect appropriate interventions. Any surveillance program should be introduced in a stepwise manner as the blood transfusion service develops.
Donor management: Malaysia and the western Pacific region

Ayob Y

Dev Biol (Basel), 2005;120:131-7.
PMID: 16050166
Fulltext Factor IX mutations in haemophilia B patients in Malaysia: a preliminary study

Balraj P, Ahmad M, Khoo AS, Ayob Y

Malays J Pathol, 2012 Jun;34(1):67-9.
PMID: 22870602 MyJurnal

Haemophilia B is caused by coagulation defects in the factor IX gene located in Xq27.1 on the X chromosome. Identification of mutations contributing to defective factor IX may be advantageous for precise carrier and prenatal diagnosis. We studied 16 patients from 11 families, consisting of 8 patients of the Malay ethnic group, of which 6 were siblings. Factor IX mutations have not been previously reported in the Malay ethnic group. The functional region of the factor IX gene was sequenced and mutations were identified in either the exon or intronic regions in 15 of the patients. One novel mutation, 6660_6664delTTCTT was identified in siblings with moderate form of haemophilia B. Mutations identified in our patients when linked with disease severity were similar to findings in other populations. In summary, this preliminary data will be used to build a Malaysian mutation database which would facilitate genetic counseling.
Diversity of hepatitis B virus infecting Malaysian candidate blood donors is driven by viral and host factors

Meldal BH, Bon AH, Prati D, Ayob Y, Allain JP

J Viral Hepat, 2011 Feb;18(2):91-101.
PMID: 20196797 DOI: 10.1111/j.1365-2893.2010.01282.x

Malaysia is a medium endemic country for hepatitis B virus (HBV) infection but little is known about HBV strains circulating in Malaysian blood donors. Viral load, HBsAg concentrations and nested PCR products from 84 HBV surface antigen (HBsAg) positive samples were analysed in detail. Median viral load was 3050 IU/mL and median HBsAg 1150 IU/mL. Fifty-six full genome, 20 pre-S/S, 1 S gene and six basic core promoter/precore-only sequences were obtained. Genotypes B and C were present at a ratio of 2:1, and two genotype D samples were obtained, both from donors of Indian background. Phylogenetically, genotype B was more diverse with subgenotypes B2-5, B7 and B8 present, while most genotype C strains were from subgenotype C1. Genotypes B and C were equally frequent in ethnic Malays, but 80% of strains from Chinese were genotype B. HBsAg concentrations were higher in genotype C than in genotype B, in Chinese than Malays and in donors under the age of 30. HBV vaccine escape substitutions (P120S/T, I126N and G145G) were present in six strains. In the large surface protein, immuno-inactive regions were more mutated than CD8 epitopes and the major hydrophilic region. Strains of genotype B or from ethnic Malays had higher genetic diversity than strains of genotype C or from Chinese donors. Hence HBV strains circulating in Malaysia are phylogenetically diverse reflecting the ethnic mix of its population. Ethnic Malays carry lower HBsAg levels and higher genetic diversity of the surface antigen, possibly resulting in more effective immune control of the infection.
Inherited thrombophilia markers in Malaysian women with recurrent fetal loss

Ayadurai T, Ayob Y, Muniandy S, Omar SZ

Thromb. Haemost., 2007 Nov;98(5):1152-4.
PMID: 18000628
Fulltext Psychometric properties of the faces version of the Malay-modified child dental anxiety scale

Esa R, Hashim NA, Ayob Y, Yusof ZY

BMC Oral Health, 2015 Mar 10;15:28.
PMID: 25886943 DOI: 10.1186/s12903-015-0013-y

BACKGROUND: To evaluate the psychometric properties of the faces version of the Modified Child Dental Anxiety Scale (MCDASf) Malay version in 5-6 and 9-12 year-old children.
METHODS: The MCDASf was cross culturally adapted from English into Malay. The Malay version was tested for reliability and validity in 3 studies. In the Study 1, to determine test-retest reliability of MCDASf scale, 166 preschool children aged 5-6 years were asked to rank orders five cartoons faces depicting emotions from 'very happy' to 'very sad' faces on two separate occasions 3 weeks apart. A total of 87 other 5-6 year-old children completed the Malay-MCDASf on two separate occasions 3 weeks apart to determine test-retest reliability for Study 2. In study 3, 239 schoolchildren aged 9-12 years completed the Malay-MCDASf and the Malay-Dental Subscale of the Children Fear Survey Schedule (CFSS-DS) at the same sitting to determine the criterion and construct validity.
RESULTS: In study 1, Kendall W test showed a high degree of concordance in ranking the cartoon faces picture cards on each of the 2 occasions (time 1, W = 0.955 and time 2, W = 0.954). The Malay-MCDASf demonstrated moderate test-retest reliability (Intraclass correlation coefficient = 0.63, p <0.001) and acceptable internal consistency for all the 6 items (Cronbach's alpha = 0.77) and 8 items (Cronbach's alpha = 0.73). The highest MCDASf scores were observed for the items 'injection in the gum' and 'tooth taken out' for both age groups. The MCDASf significantly correlated with the CFSS-DS (Pearson r = 0.67, p < 0.001).
CONCLUSIONS: These psychometric findings support for the inclusion of a cartoon faces rating scale to assess child dental anxiety and the Malay-MCDASf is a reliable and valid measure of dental anxiety in 5-12 year-old children.
Fulltext A retrospective review of cryoprecipitate transfusion practice in Kuala Lumpur Hospital

Iliassa II, Mohammad WM, Tan JJ, Ayob Y

Asian J Transfus Sci, 2016 Jul-Dec;10(2):145-9.
PMID: 27605853 DOI: 10.4103/0973-6247.187934

BACKGROUND: Cryoprecipitate is generally used to treat bleeding patients with hypofibrinogenemia, and the transfusion decision is guided based on published guidelines.
AIM: This study aimed to evaluate the practice appropriateness in accordance to cryoprecipitate transfusion guidelines in Hospital Kuala Lumpur.
METHODOLOGY: This cross-sectional study of 117 cryoprecipitates transfused adult patients was conducted in Kuala Lumpur Hospital from January to June 2012. The compliance of the indication of cryoprecipitate was considered as appropriate if indicated for patients who have hypofibrinogenemia (<1.0 g/L) with bleeding, or otherwise inappropriate if pretransfusion fibrinogen level was more than 1.0 g/L, pretransfusion fibrinogen level was not examined and posttransfusion fibrinogen level more than 1.5 g/L.
RESULTS: Most of the cryoprecipitate prescriptions were found to be inappropriate, which read 81.2% (95% confidence interval = 0.740, 0.880). Patients who underwent neurovascular surgery were the major recipient of cryoprecipitate, but majority of the prescription was found not appropriate. The decision to transfuse cryoprecipitate was found mostly appropriate when was guided by fibrinogen (52.2%), but the percentage dropped to 10.6% when pretransfusion fibrinogen test was not performed. Regrettably, only 19.7% of total cryoprecipitate were given based on pretransfusion fibrinogen level.
KEYWORDS: Appropriateness; bleeding; cryoprecipitate transfusion; guideline
WITHDRAWN: Rh genotypes among Malaysian blood donors

Musa RH, Hassan A, Ayob Y, Yusoff NM

Transfus Apher Sci, 2014 Dec 12.
PMID: 26144905 DOI: 10.1016/j.transci.2014.12.001

This article has been withdrawn at the request of the author and editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.
Fulltext Molecular basis of Rh blood group system in the Malaysian population

Musa RH, Muhamad NA, Hassan A, Ayob Y, Yusoff NM

Asian J Transfus Sci, 2015 Jan-Jun;9(1):48-54.
PMID: 25722573 DOI: 10.4103/0973-6247.150951

Rh molecular studies have been previously mainly conducted in Caucasians and African population. There is a limited data on the molecular basis for Rh genotypes among Asians.
Fulltext Quality indicators for discarding blood in the National Blood Center, Kuala Lumpur

Morish M, Ayob Y, Naim N, Salman H, Muhamad NA, Yusoff NM

Asian J Transfus Sci, 2012 Jan;6(1):19-23.
PMID: 22623837 DOI: 10.4103/0973-6247.95045

The implementation of quality system and continuous evaluation of all activities of the Blood Transfusion Services (BTS) can help to achieve the maximum quantity and quality of safe blood. Optimizing blood collection and processing would reduce the rate of discard and improve the efficiency of the BTS. The objective of this study is to determine the rate of discard of blood and blood component and identify its reasons at the National Blood Centre (NBC), Kuala Lumpur, during the year of 2007 in order to introduce appropriate intervention.
Fulltext Red cell phenotyping of blood from donors at the National blood center of Malaysia

Musa RH, Ahmed SA, Hashim H, Ayob Y, Asidin NH, Choo PY, et al.

Asian J Transfus Sci, 2012 Jan;6(1):3-9.
PMID: 22623834 DOI: 10.4103/0973-6247.95042

Human blood groups are polymorphic and inherited integral structures of the red cell membrane. More than 300 red cell antigens have been identified and further categorized into 30 major discrete systems. Their distribution varies in different communities and ethnic groups.
Occult hepatitis B infection in blood donors from South East Asia: molecular characterisation and potential mechanisms of occurrence

Candotti D, Lin CK, Belkhiri D, Sakuldamrongpanich T, Biswas S, Lin S, et al.

Gut, 2012 Dec;61(12):1744-53.
PMID: 22267593 DOI: 10.1136/gutjnl-2011-301281

To investigate the molecular basis of occult hepatitis B virus (HBV) infection (OBI) in Asian blood donors.
Hemophilia treatment in developing countries: products and protocols

Srivastava A, You SK, Ayob Y, Chuansumrit A, de Bosch N, Perez Bianco R, et al.

Semin Thromb Hemost, 2005 Nov;31(5):495-500.
PMID: 16276456

The most important aspect of management of hemophilia is to provide adequate replacement of safe clotting factor concentrates to prevent or treat bleeding episodes. There has been considerable progress in many countries in the developing world with regard to this aspect of care. However, very little data are available in the literature on the types of products being used for factor replacement and the doses being administered for control or treatment of bleeding in different countries. These data are important to document because only then can data from different centers be compared. This article provides data from seven countries: Korea, Malaysia, Thailand, Venezuela, Argentina, Iran, and India. It shows that there is wide variability not only in the types of products used (plasma to recombinant factor concentrates) but also in the doses administered (minimal to very high) for similar indications. Prospective documentation of data on musculoskeletal outcome at these centers and correlation with dose of factor replacement could help identify different models of care. Comparing such data and collating the experience in different countries could be useful for optimizing care and establishing cost-effective models. The combined experience in the developing world in providing hemophilia services should be used to define standards of care that are practical and to set achievable goals.
Mutational Profiles of F8 and F9 in a Cohort of Haemophilia A and Haemophilia B Patients in the Multi-ethnic Malaysian Population

Zahari M, Sulaiman SA, Othman Z, Ayob Y, Karim FA, Jamal R

Mediterr J Hematol Infect Dis, 2018;10(1):e2018056.
PMID: 30210749 DOI: 10.4084/MJHID.2018.056

Background: Haemophilia A (HA) and Haemophilia B (HB) are X-linked blood disorders that are caused by various mutations in the factor VIII (F8) and factor IX (F9) genes respectively. Identification of mutations is essential as some of the mutations are associated with the development of inhibitors. This study is the first comprehensive study of the F8 mutational profile in Malaysia.
Materials and methods: We analysed 100 unrelated HA and 15 unrelated HB patients for genetic alterations in the F8 and F9 genes by using the long-range PCR, DNA sequencing, and the multiplex-ligation-dependent probe amplification assays. The prediction software was used to confirm the effects of these mutations on factor VIII and IX proteins.
Results: 44 (53%) of the severe HA patients were positive for F8 intron 22 inversion, and three (3.6%) were positive for intron one inversion. There were 22 novel mutations in F8, including missense (8), frameshift (9), splice site (3), large deletion (1) and nonsense (1) mutations. In HB patients, four novel mutations were identified including the splice site (1), small deletion (1), large deletion (1) and missense (1) mutation.
Discussion: The mutational spectrum of F8 in Malaysian patients is heterogeneous, with a slightly higher frequency of intron 22 inversion in these severe HA patients when compared to other Asian populations. Identification of these mutational profiles in F8 and F9 genes among Malaysian patients will provide a useful reference for the early detection and diagnosis of HA and HB in the Malaysian population.
Fulltext Factors influencing transfusion requirement in patients undergoing first-time, elective coronary artery bypass graft surgery

Mazlan AM, Ayob Y, Hussein AR, Namasiwayam TK, Wan Mohammad WMZ

Asian J Transfus Sci, 2017 Jul-Dec;11(2):95-101.
PMID: 28970674 DOI: 10.4103/ajts.AJTS_51_16

CONTEXT: Coronary artery bypass graft (CABG) operation is associated with high frequency of allogeneic blood transfusion due to the acquired hemostatic challenges in patients undergoing CABG. However, allogeneic blood transfusion carries risks of infection, adverse reaction, and mortality as well as prolonged hospital stay and increased hospital cost. It is important to identify patients who require blood transfusion to mitigate their risk factors and reduce the chance of exposure to allogeneic blood.

AIMS: This study was conducted to evaluate factors that influence the decision to transfuse red cell in first-time elective CABG patients.

SETTINGS AND DESIGN: This was a cross-sectional study based on a retrospective record review. The study was done in the National Heart Institute.

MATERIALS AND METHODS: All patients who underwent first-time elective CABG were included in this study. Variables analyzed include age, gender, body weight, preoperative hemoglobin (Hb) level, patients' comorbidities, and other clinical parameters.

STATISTICAL ANALYSIS USED: Data were analyzed using SPSS software version 20.

RESULTS: A total of 463 patients underwent first-time elective CABG during the period of the study. Three hundred and eighty-six (83.4%) patients received red cell transfusion. From multiple logistic regression analysis, only age (odds ratio [OR] = 1.040, 95% confidence interval [CI]: 1.003, 1.077, P = 0.032), body weight (OR = 0.951, 95% CI: 0.928, 0.974, P < 0.001), Hb level (OR = 0.500, 95% CI: 0.387, 0.644, P < 0.001), and cardiopulmonary bypass time (OR = 1.013, 95% CI: 1.004, 1.023, P < 0.001) were the significant independent predictors of red cell transfusion.

CONCLUSIONS: By stratifying patients according to their risk factor for red cell transfusion, the high-risk patients could be recognized and should be enrolled into effective patient blood management program to minimize their risk of exposure to allogeneic blood transfusion.
Study of the D-- phenotype reveals erythrocyte membrane alterations in the absence of RHCE

Flatt JF, Musa RH, Ayob Y, Hassan A, Asidin N, Yahya NM, et al.

Br J Haematol, 2012 Jul;158(2):262-273.
PMID: 22571328 DOI: 10.1111/j.1365-2141.2012.09149.x

Red cells with the D-- phenotype do not express the RHCE protein because of mutations in both alleles of the RHCE gene. At present, little is known of the effect this has on the normal function of erythrocytes. In this study a group of five families belonging to a nomadic tribe in Malaysia were identified as carriers of the D-- haplotype. Analysis of homozygous individuals' genomic DNA showed two separate novel mutations. In four of the families, RHCE exons 1, 9 and 10 were present, while the 5th family possessed RHCE exons 1-3 and 10. Analysis of cDNA revealed hybrid transcripts, suggesting a gene conversion event with RHD, consistent with previously reported D-- mutations. Immunoblotting analysis of D-- erythrocyte membrane proteins found that Rh-associated glycoprotein (RHAG) migrates with altered electrophoretic mobility on sodium dodecyl sulphate polyacrylamide gel electrophoresis, consistent with increased glycosylation. Total amounts of Rh polypeptide in D-- membranes were comparable with controls, indicating that the exalted D antigen displayed by D-- red cells may be associated with altered surface epitope presentation. The adhesion molecules CD44 and CD47 are significantly reduced in D--. Together these results suggest that absence of RHCE polypeptide alters the structure and packing of the band 3/Rh macrocomplex.
Heterosubtypic anti-avian H5N1 influenza antibodies in intravenous immunoglobulins from globally separate populations protect against H5N1 infection in cell culture

Sullivan JS, Selleck PW, Downton T, Boehm I, Axell AM, Ayob Y, et al.

J Mol Genet Med, 2009 Dec 23;3(2):217-24.
PMID: 20076794

With antigenically novel epidemic and pandemic influenza strains persistently on the horizon it is of fundamental importance that we understand whether heterosubtypic antibodies gained from exposures to circulating human influenzas exist and can protect against emerging novel strains. Our studies of IVIG obtained from an infection-naive population (Australian) enabled us to reveal heterosubtypic influenza antibodies that cross react with H5N1. We now expand those findings for an Australian donor population to include IVIG formulations from a variety of northern hemisphere populations. Examination of IVIGs from European and South East-Asian (Malaysian) blood donor populations further reveal heterosubtypic antibodies to H5N1 in humans from different global regions. Importantly these protect against highly pathogenic avian H5N1 infection in vitro, albeit at low titres of inhibition. Although there were qualitative and quantitative differences in binding and protection between globally different formulations, the heterosubtypic antibody activities for the respective IVIGs were in general quite similar. Of particular note because of the relative geographic proximity to the epicentre of H5N1 and the majority of human infections, was the similarity in the antibody binding responses between IVIGs from the Malayan peninsula, Europe and Australia. These findings highlight the value of employing IVIGs for the study of herd immunity, and particularly heterosubtypic antibody responses to viral antigens such as those conserved between circulating human influenzas and emerging influenza strains such as H5N1. They also open a window into a somewhat ill defined arena of antibody immunity, namely heterosubtypic immunity.

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