Introduction: Hemoglobin Constant Spring (HbCS) is often missed due to almost normal red cells indices and is present at a low level in peripheral blood. However, analysis of blood samples using capillary electrophoresis (CE) is able to differentiate between heterozygous and homozygous state of HbCS. Methods: An eight-year-old Malay girl presented with severe anaemia and hepatosplenomegaly following a viral infection. The diagnosis of homozygous HbCS was made from Hb analysis by CE which showed a small peak (5.3%) at Hb CS zone. His brother had similar CE findings while both of her father and mother showed much smaller peaks (0.7% and 0.4% respectively) at similar zone which were consistent with heterozygous HbCS. All findings were confirmed by few molecular analysis techniques. Conclusion: This case highlights the importance of detection of homozygous HbCS by CE. CE is useful as a fast screening method for detection of HbCS in hematology laboratory where molecular analysis is not available and patient with homozygous HbCS has higher risk to develope acute hemolysis when having infection. Keywords: Capillary electrophoresis, Hb Constant Spring, Homozygous state.

Thalassaemia is one of the most common autosomal recessive blood disorders in the world and its carrier status is prevalent in nearly 15% of Malaysian population. The global and economic burden for lifelong care of those affected increases every year. Currently, there is no policy on thalassaemia-carrier screening for couples prior to marriage besides HIV/AIDS screening in Malaysia. Other countries such as Iran, Iraq, Turkey, Bahrain and Saudi Arabia have established a policy for thalassaemia prevention by conducting premarital thalassaemia screening. Zero thalassaemia cases in new-born child in Cyprus have proven that thalassaemia can be prevented. This study aimed to investigate the willingness of premarital Malays on premarital thalassaemia screening. A set of questionnaire was distributed to 57 persons at premarital course sites and wedding fairs and expositions held in Kuala Lumpur and Selangor. Components in the questionnaire included: 1) demographic 2) knowledge about thalassaemia, signs and screening method 3) attitudes towards thalassaemia premarital screening 4) practices of premarital thalassaemia screening. Analysis for the questionnaire was performed using IBM SPSS Statistics 23.0. A majority of the participants (75.44%) have never heard of thalassaemia as a medical condition. However, at least half of the participants (56.14%) agreed that premarital screening is needed to know their status of thalassaemia. In terms of facilities provided, widely covered campaigns about facilities of the screening test is also one of the factors that could encourage people to do premarital thalassaemia screening (35.09%). Even though premarital thalassaemia screening is not an obligation, 50.88% of participants agreed that it is important. The main reason people refused to do premarital thalassaemia screening was because they were afraid to know the test result and how it may affect their lives. Although preliminary, we have demonstrated that the level of knowledge concerning thalassemia among Malay Malaysians is still low. This may contribute to the low awareness about the effects of the disease and the importance of premarital thalassemia screening. However, most participants agreed that it is beneficial to perform the premarital thalassemia screening to identify individuals at risk of this disease. Nevertheless, many factors need to be taken into consideration if premarital thalassaemia screening is to be implemented in Malaysia as a national policy.

Clinical history, morphological appearance and cytogenetic data are required in identifying cases of MyelodysplasticSyndrome (MDS). However, this clonal stem cell disorder is still widely heterogenous and multiple tools are utilized in determining the diagnosis and prognosis. The current approaches in diagnosis are inherently subjective and lack of sensitivity. Over the years, altered maturation patterns using flow cytometry analysis have been reported to be useful for identification of MDS. This systematic review aims to assess the sensitivity of maturation pattern in obtaining MDS diagnosis. Electronic databases (MEDLINE, PROQUEST, OVID, Scopus, Web of Science) searched were yielded 677 articles. Snowballing was also employed. Two reviewers assessed each article independently using the following inclusion criteria: all types of MDS; WHO or FAB classification; diagnosis; immunophenotyping. Nineteen papers that met our inclusion criteria were analysed on the maturation pattern using flow cytometry. Samples used were bone marrow aspiration and prepared using either whole blood lysis or Ficoll-density gradient centrifugation. The most studied lineage in diagnosing MDS using maturation pattern is myeloid mainly looking on the CD34+, CD11b/CD16, CD13/CD16 and CD235a/CD71 expression pattern. Five studies showed sensitivity between 70 to 98 percent. Maturation pattern has shown high sensitivity and may be used as an ancillary technique for the diagnosis of MDS. However, flow cytometry strategies employed lack of standardization in assay, scoring system, and on how flow cytometry data have been analysed. Thus, more study need to be done within laboratory and multi-centre study to ensure validity and reliability of maturation pattern as an adjunct test.

The Siriraj I Gγ(Aγδβ)0 -thalassaemia is a novel mutation involving a 118kb deletion of the β-globin gene cluster. It was first reported in 2012 in two unrelated families from the southern part of Thailand. The carriers in the heterozygous state are clinically asymptomatic. Nonetheless, its complex interaction with other β-thalassaemia could give rise to different clinical phenotypes, ranging from mild thalassaemia intermedia to thalassaemia major. We report here a case of a six-year-old Malay boy, presented with pallor, growth failure and hepatosplenomegaly. His haemoglobin at presentation was 9.2g/dL with a mean cell haemoglobin of 22.6pg and a mean cell volume of 69.9fl. His peripheral blood smear showed features of thalassaemia intermedia. Haemoglobin (Hb) analysis revealed markedly raised Hb F (83%), normal HbA2 levels and absent HbA. Deoxyribonucleic acid (DNA) analysis showed compound heterozygous IVS1-1 (G→T) β-globin gene mutation and Siriraj I Gγ(Aγδβ)0 -deletion (genotype βIVS1-1/ β Siriraj I deletion). Both his father and elder sister are carriers of Siriraj I Gγ(Aγδβ)0 -thalassaemia while his mother carries IVS1-1 (G→T) gene mutation. Clinically, the patient is transfusion dependent on six weekly regime. To the best of our knowledge, this is the first reported case in Malaysia involving unique Siriraj I Gγ(Aγδβ)0 -thalassaemia and IVS1-1 (G→T) in a compound heterozygous state. In summary, detection of Siriraj I Gγ(Aγδβ)0 -thalassaemia is essential as this deletion can lead to severe disease upon interaction with a β-thalassemia point mutation as demonstrated in our case. The establishment of effective carrier screening and genetic counselling is important to prevent its adverse consequences.

Introduction: Myelodysplastic syndrome (MDS) is clonal haematopoietic stem cell disorder characterized by peripheral pancytopenia, despite the normo- or hypercellularity appearance of bone marrow. Accelerated apoptosis has been postulated to be involved in the pathogenesis of MDS, leading to ineffective hematopoiesis. The aim of this systematic review was to study the role of apoptosis in the pathogenesis of MDS. Methodology: We searched Proquest and Ebscohost databases up to March 2015. The search yielded 966 articles using keywords; Myelodysplastic Syndrome or MDS or Myelodysplasia and apopto* or cell death. Results/Discussion: A total of 18 experimental papers have been found to meet the inclusion criteria. Apoptosis has been found to occur in CD34 positive, mononuclear cells as well as stromal cells of the bone marrow microenvironment with high expressions of pro-apoptotic mediators such as Fas/Fas L, TNF-α, caspase family proteins and Granzyme-B. Bcl-2, p53 mediators and mc11 and bfl1 genes are highly expressed to compensate the apoptosis process while allowing the accumulation of blast cells within the bone marrow. Mitocondrial membrane potential, phosphatidylserine expression and DNA fragmentation act as a marker to quantify the level of apoptosis. Clonogenic assay with appropriate apoptosis inhibitors resulted in significant growth of progenitor cells. In conclusion, apoptosis is involved in various stages of MDS development. Apoptosis is up-regulated at the early stage of MDS and is diminished with disease progression.

Team-based learning (TBL) is relatively new in medical education and has yet to be implemented in Malaysia. The main purpose of TBL is to change the classroom experience from acquiring to applying knowledge in a team. The aim of this study is to identify the student’s perception of TBL and the impact on the student’s learning in Universiti Sains Islam Malaysia (USIM). The TBL pedagogy was imparted into the teaching of Haematology module among the 3rd year medical students of USIM. Part of the face-to-face teaching sessions (25%) was changed to online learning packages while the tutorial and practical sessions were transformed into readiness assurance tests (RATs) and application exercises. The TBL implementation and the students’ performance were observed closely and at the end of the module, a feedback form was distributed to the students (n = 79). Data was analysed using SPSS version 19.0. We found that TBL encouraged students to work more seriously and effectively in teams (93.59%). They are comfortable working in teams and satisfied with the team members’ participation (98.72%). They agreed that TBL enhanced their understanding, evidenced by improvement in the tutorial marks (98.72%). TBL also improves their communication skill and self-confidence (84.42%). In general, they preferred the TBL compared to the traditional method (89.61%). Many are not comfortable with online learning and would appreciate more face-toface lecture sessions (52.56%). However, they commented that adequate facilities are required for an effective TBL (94.87%). In conclusion, students’ perception and outcome assessment showed promising results and should be considered for implementation. Keywords: Medical education, TBL, Pedagogy, Outcome, Assessment

In recent years there has been a rapid growth of the halal pharmaceutical industry, especially in the supply chain of solid oral dosage forms of medication. This article outlines aspects of the Halal Management System (HMS) in the development and production of halal pharmaceuticals. It explains the needs and requirements of HMS and identifies the challenges faced in implementation. The article outlines aspects of executions and hurdles encountered when standardizing halal certifi cation. The article also highlights the need for systematic traceability systems and effective product recall mechanisms to ensure adherence to halal requirements. It also highlights the grey areas for halal in terms of pharmaceutical manufacture that are brought about by use of non-halal raw materials, e.g. alcohol, gelatine, glycerin, lecithin, glutamic acid and stearates.