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Background: Alloimmunization is a known complication following repeated red blood cell transfusions. However, the associated factors of RBC alloimmunization are different among blood recipient groups. This study aimed to determine the associated factors of red blood cell alloimmunization among solid cancer patients in Hospital USM. Material and Methods: This cross-sectional study involved 322 adult solid cancer patients screened for red cell alloantibodies in our centre from October 2016 until February 2019. The clinical and transfusion data were obtained from the patient’s medical record and laboratory information system (My Transfusi). The multiple logistic regression was used for analysis of potential associated factors of red blood cells alloimmunization, and p-value of less than 0.050 was considered statistically significant. Results: The patient’s mean age was 52.0 years old, with the majority were Malays (91.0%) and females (61.2%). The most common cancers were breast (32.3%) followed by gastrointestinal (16.8%) and head and neck (14.3%). The presence of metastases (adjusted OR=13.53, p=0.017), numbers of packed red cell transfusions (adjusted OR=1.12, p= 0.015), and blood group A (adjusted OR=7.45, p=0.003) were the associated factors of alloimmunization. Conclusions: Solid cancer patients with metastases, received a higher number of packed red cell transfusions, and blood group A were at higher risk for alloimmunization. Strategies to provide phenotype RBC should focus on this type of patient to prevent red blood cells alloimmunization in solid cancer patients. Bangladesh Journal of Medical Science Vol. 22 No. 02 April’23 Page : 379-384

Clinical demand for blood transfusion is endless, and patients are exposed to the risk of transfusion error at any point along the transfusion chain which lead to incorrect blood component transfused (IBCT) if the standard transfusion practices have not complied. This study aimed to determine the prevalence, sources, and causes of error among IBCT in Hospital USM. This retrospective study involved all packed red cell (PC) transfusion and reported IBCT in Transfusion Medicine Units, Hospital USM from January 2005 to December 2020. The recipient and transfusion data of IBCT were collected from the medical record and laboratory information system (MyTransfusi). A total of 193 697 PC transfusions were documented, and 14 IBCT were reported within 16 years of transfusion services. The incidence of IBCT was 1 in 13 836 of PC transfusion. Most of the IBCT contributed by ward error (64.3%). The major cause of error was patient miss identification (85.7%) either in patient sampling, blood component issuing and administration. Most ABO incompatibility IBCT (3 out of 5) end up with severe morbidity or mortality related to an acute haemolytic transfusion reaction. Most of the errors occurred in the wards. Patient misidentification is a major cause of IBCT, and it is preventable. Thus, preventive measures should emphasize on positive patient identification at every step of transfusion chain.

Autoimmune hemolyticanemia (AIHA) can be caused by a variety of etiologies. Approximately one-half of warm AIHAs are idiopathic, while the nonidiopathicetiologies include lymphoproliferative disorders, autoimmune disease, and infection-induced AIHA. AIHA may be frequently challenged by infectious complications, mainly as a result of immunosuppressive treatments administered. Here we reported an extraordinary case of Mycobacterium tuberculosis infection presented with high titer cold-agglutinin autoimmune hemolysis in an immunocompetent patient. Although being risk factors for mortality, infections are an underestimated issue in AIHA. No antecedent case of pulmonary tuberculosis associated with cold agglutinin disease has been reported from Malaysia. Bangladesh Journal of Medical Science Vol. 21 No. 03 July’22 Page: 754-757

Background: Group O blood donor is more readily available and is frequently used as a universal red cell donor and emergency O whole blood (EM O) for exchange transfusion in neonates. Sera from group O donors contains two separable haemolysin antibodies, anti-A and anti-B, and a cross-reacting antibody called anti-A, B (mostly IgG). The presence of haemolysins in the donors may lead to haemolysis in the recipients. Objectives: This study aims to determine the prevalence of anti-A and anti B haemolysins and titer among group O donors that we screened for emergency group O (EM O) whole blood Methodology: A cross sectional study was done to determine the prevalence of anti-A and anti B haemolysin and titer among group O blood donors screened for EM O whole blood for exchange transfusion in neonates at a teaching hospital from January to December 2018. Samples of 350 voluntary group O regular donors were selected for ABO antibodies titration and haemolysin test using the conventional tube technique at room temperature. Donors were screened for titer of 1:50 and 1:100 only. ABO antibody titer of ≥1:100 was considered as a high titer and not suitable for exchange transfusion. Titer of ≤1:50 were labeled as EM O whole blood and will be suitable for exchange transfusion. Results: A total of 350 group O blood donors were screened for the anti A and anti B haemolysin and titer. The majority of blood group O donors were male (n=215, 61%) and were age from 18-30 years old (51%). Malay was the predominant group (83%). About 52.9% of the donors were low titer (≤1:50), and 47.1% were high titer (≥1:100). Low titer was seen predominantly among male donors (61.8%). The prevalence of haemolysins in group O donors was 5.4% (n=19). Anti A and anti B haemolysins were seen in 0.57% and 2.28% of the donors, respectively, while donors having both A and B haemolysins in their sera was 2.57%. Conclusion: Prevalence of anti-A and anti-B haemolysins were low among group O blood donors. However, a significant percentage of group O donors have high titer of anti-A or anti-B. Therefore, despite the labour intensiveness of haemolysis titration technique and the frequent transfusion of group O blood for exchange transfusion, there is the need to routinely screen our donors for haemolysins in order to identify those posing the greatest risk to recipients. Bangladesh Journal of Medical Science Vol. 21 No. 02 April’22 Page : 368-372

Haemophagocytic lymphohistiocytosis (HLH) is a rare disease but potentially life threatening clinical syndrome. It is caused by a multisystemic hyperinflammatory process secondary to severe hypercytokinemia with excessive and uncontrolled activation of the immune response. We report a case of familial HLH with no apparent causes in 6 months-old Malay girl presented with recurrent fever associated with severe anaemia and bleeding tendency requiring extensive treatment but refractory to the treatment which lead to mortality due to neutropenic sepsis indicating of poor prognosis of this disease. This familial type of HLH should be suspected in all children after excluding all the secondary causes with collective laboratory features and requiring extensive management as it associated with high mortality. Bangladesh Journal of Medical Science Vol. 21(1) 2022 Page : 196-200

Severe haemolytic disease of foetus and newborn (HDFN) is commonly caused by anti-D, anti-c and anti-K alloimmunisation. However, anti-c associated HDFN are infrequent because the majority of infants are relatively often c-negative. This case report describes a severe HDFN due to anti-c alloimmunisation in a multiparous Rhesus D positive mother. The baby was delivered prematurely at 32 weeks of gestation and unable to survive due to hydrops foetalis. Failure to detect anti-c alloimmunisation at the early antenatal period and unknown previous RBC alloimmunisation status were the main reasons for poorly suspicion of HDFN, which lead to improper foetal management and end up with foetal loss. Thus, routine antenatal RBC antibody screening during the early antenatal period is recommended for every pregnant woman with a history of HDFN or at risk for alloimmunisation for early detection and management of HDFN to prevent severe related morbidity or mortality.

Heterozygous haemoglobin E (Hb E) with deletional alpha (α)-thalassaemia is commonly seen in Southeast Asia including Kelantan, a Northeastern state of Malaysia. Studies in Malaysia showed that Hb E is the commonest among Malay Kelantan, Penang and Senoi group of Orang Asli [1-5]. This study aimed to compare the haematological parameters (Hb, RBC, MCV, MCH, RDW and Hb E) among the heterozygous Hb E with deletional α-thalassaemia subjects. This study also intended to ascertain a cut-off value for heterozygous Hb E with deletional α-thalassaemia using automated capillary electrophoresis method. A cross-sectional study was conducted involving secondary data collection of 219 samples of heterozygous Hb E with possible α-thalassaemia from all districts of Kelantan. Full blood count (FBC) was analysed using Sysmex XN 3000 automated blood cell analyser (Kobe, Japan). Hemoglobin (Hb) analysis was performed using automated CE system (Capillarys2; Sebia, France). Molecular characterisation was performed using multiplex gap-PCR and ARMS-PCR to detect both deletional and non-deletional α-thalassaemia, respectively. Qualitative data were expressed as frequency and percentage while quantitative data were expressed as mean, ± SEM and median. One-way ANOVA was used to test for mean Hb level, RBC count, MCV level, MCH level, and RDW level differences among six groups of heterozygous Hb E with concurrent deletional alpha thalassaemia in this study. The ROC curve was used to determine the cut-off point for Hb E level. Eighty-nine samples of heterozygous Hb E were confirmed to have concurrent deletional α-thalassaemia. Heterozygous Hb E with heterozygous α3.7 gene deletion was the most common deletional α-thalassaemia observed in 56 samples (62.9%) and followed by heterozygous SEA gene deletion which were detected in 21 samples (23.6%). The haematological parameters showed there was a significant difference between groups. The cut-off point for Hb E level for predicting heterozygous Hb E with deletional α-thalassaemia from CE method was 24.7% (Table 1). The diagnostic performance for the cut-off point for Hb E level showed sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 100% for all. This cut-off value can be used in assisting the selection of heterozygous Hb E individual to proceed with DNA analysis for α-thalassaemia.

Background : Deletions in the β-globin gene cluster are usually rare, problematic to detect, and subsequently possess a challenge in many diagnostic laboratories. They are normally related to the heterozygous of the delta beta (δβ) thalassemia, hereditary persistence of fetalhemoglobin (HPFH) and some of the hemoglobin variants. These disorders are typically presented by elevated levels of hemoglobin F (Hb F), but with low to normal hemoglobin A2 (Hb A2). However, despite their existence, there is still a limited number of studies focusing on this area, hence no definitive diagnosis could be conclusively established. Therefore, this pilot study was carried out to fill this knowledge gap. Methods: In this study, screening of the selected deletional mutations in the β-globin gene cluster among patients with Hb F (>1%) and Hb A2 (

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.

The Global Globin Network (GGN) is a project-wide initiative of the Human Variome/Global Variome Project (HVP) focusing on haemoglobinopathies to build the capacity for genomic diagnosis, clinical services, and research in low- and middle-income countries. At present, there is no framework to evaluate the improvement of care, treatment, and prevention of thalassaemia and other haemoglobinopathies globally, despite thalassaemia being one of the most common monogenic diseases worldwide. Here, we propose a universally applicable system for evaluating and grouping countries based on qualitative indicators according to the quality of care, treatment, and prevention of haemoglobinopathies. We also apply this system to GGN countries as proof of principle. To this end, qualitative indicators were extracted from the IthaMaps database of the ITHANET portal, which allowed four groups of countries (A, B, C, and D) to be defined based on major qualitative indicators, supported by minor qualitative indicators for countries with limited resource settings and by the overall haemoglobinopathy carrier frequency for the target countries of immigration. The proposed rubrics and accumulative scores will help analyse the performance and improvement of care, treatment, and prevention of haemoglobinopathies in the GGN and beyond. Our proposed criteria complement future data collection from GGN countries to help monitor the quality of services for haemoglobinopathies, provide ongoing estimates for services and epidemiology in GGN countries, and note the contribution of the GGN to a local and global reduction of disease burden.

Thalassemia, an inherited quantitative globin disorder, consists of two types, α– and β–thalassemia. β–thalassemia is a heterogeneous disease that can be asymptomatic, mild, or even severe. Considerable research has focused on investigating its underlying etiology. These studies found that DNA hypomethylation in the β–globin gene cluster is significantly related to fetal hemoglobin (HbF) elevation. Histone modification reactivates γ-globin gene expression in adults and increases β–globin expression. Down-regulation of γ–globin suppressor genes, i.e., BCL11A, KLF1, HBG-XMN1, HBS1L-MYB, and SOX6, elevates the HbF level. β–thalassemia severity is predictable through FLT1, ARG2, NOS2A, and MAP3K5 gene expression. NOS2A and MAP3K5 may predict the β–thalassemia patient’s response to hydroxyurea, a HbF-inducing drug. The transcription factors NRF2 and BACH1 work with antioxidant enzymes, i.e., PRDX1, PRDX2, TRX1, and SOD1, to protect erythrocytes from oxidative damage, thus increasing their lifespan. A single β–thalassemia-causing mutation can result in different phenotypes, and these are predictable by IGSF4 and LARP2 methylation as well as long non-coding RNA expression levels. Finally, the coinheritance of β–thalassemia with α–thalassemia ameliorates the β–thalassemia clinical presentation. In conclusion, the management of β–thalassemia is currently limited to genetic and epigenetic approaches, and numerous factors should be further explored in the future.

Background Unsafe blood products may cause transfusion-transmissible infections. This study aimed to evaluate the knowledge and perceptions of blood donors regarding blood safety. Methods This was a cross-sectional study conducted in the Kelantan state of Malaysia. The questionnaire comprised 39 questions that covered areas such as donors' social demographic information, knowledge of transfusion-transmitted diseases, blood screening and donor eligibility and perceptions towards blood safety. The knowledge score was categorised as good or poor. Results Of the 450 distributed questionnaires, 389 were suitable for analysis. Only 18.5% of the donors had good knowledge, with 81.5% having poor knowledge. Less than 30% were aware that people with multiple sexual partners, bisexual people and male homosexual people are permanently deferred from blood donation. Only 29.4% agreed that donors are responsible if their blood causes infection. Furthermore, 39.3% assumed that they could check their HIV status through blood donation, and 10.3% and 5.4% of the respondents believed that donors are free from infection if they wear a condom during sex or only have oral sex when involved in prostitution, respectively. Conclusion Poor knowledge and notable misperceptions concerning safe blood donation were found among blood donors. The Ministry of Health should incorporate safe blood education in future public awareness programmes.

Blood transfusion is a fundamental and life-saving procedure where the consequence of errors can be fatal. Nurses’ knowledge plays an essential role in ensuring quality and safety in blood transfusion. The objective of this study was to assess blood transfusion-associated knowledge of tertiary hospital nurses on the east coast of Malaysia. This was a cross-sectional study with 200 registered nurses involved in blood transfusion procedures at Hospital Universiti Sains Malaysia. The knowledge of the nurses was evaluated by using the routine blood transfusion knowledge questionnaire based on five parts, and &lt, 50%, 50–74%, or ≥75% of the knowledge was considered as poor, moderate, or high, respectively. Based on the scoring system, the overall knowledge of blood transfusion among Malaysian nurses (33.2 ± 8.4 years) was estimated to be 54.9 ± 7.6%. In individual items, the scoring was 81.0%, 45.4%, 49.2%, 63.0%, and 90.0% in knowledge prior to blood transfusion, on pre-transfusion, on post-transfusion, on complications, and on transfusion policy, respectively. The findings of this study indicated that most of the nurses’ overall knowledge of blood transfusion was at a moderate level, therefore, training courses and continuous medical education are warranted to improve knowledge and skills of the nurses to ensure good practices of blood transfusion.

Thalassemia is the most common genetic disorder in Southeast Asia. In this study, we aimed to evaluate the prevalence of β-thalassemia (β-thal) and suspected β hemoglo-bin (Hb) variants and their h...

Level of HbA2 more than 4% is the reliable parameter to identify β- thalassemia carrier. However, in some cases the level is not typically increased hence leading to diagnostic dilemma. Thus the objectives of this study were to evaluate the existence of β- thalassemia among borderline HbA2 sample. Out of 11,790 samples received for thalassemia screening, 405 (3.4%) were found to have borderline HbA2 level. Out of this, 117(28.9%) samples were selected by simple random sampling for PCR. Multiplex ARMS-PCR was used to detect β-globin gene mutation and multiplex gap PCR for α-globin genes deletion. The result revealed 36 (30.8%) had β-globin gene mutations, 8 (6.8%) had α-globin gene deletions and 1 (0.9%) had coexistence of α and β-globin gene defects. The commonest gene mutation detected were CD 19 (A-G), detected from 17 (45.9%) samples, followed by 9 (24.3%) with IVS 1-1 (G-A) mutation, 5 (13.5%) with Poly A mutation and 1 (2.7%) showed CAP +1 (A-C) mutation. Two samples (5.4%) showed mutations of Poly A and CD19, 2 (5.4%) showed mutation of IVS 1-1 and CD 19 while 1 (2.7%) showed IVS 1-5 and CD 19 mutations. This study showed 10 (27.0%) positive molecular results even though the HbA2 level was at only 3.0%. There was significant number of people with HbA2 between 3.0% and 3.9% and confirmed as thalassemia carriers by PCR. This data may suggest the level of HbA2 need to be revised to ensure the success of thalassemia screening programme in our population.

The Malaysian Node of the Human Variome Project (MyHVP) is one of the eighteen official Human Variome Project (HVP) country-specific nodes. Since its inception in 9th October 2010, MyHVP has attracted the significant number of Malaysian clinicians and researchers to participate and contribute their data to this project. MyHVP also act as the center of coordination for genotypic and phenotypic variation studies of the Malaysian population. A specialized database was developed to store and manage the data based on genetic variations which also associated with health and disease of Malaysian ethnic groups. This ethnic-specific database is called the Malaysian Node of the Human Variome Project database (MyHVPDb). Currently, MyHVPDb provides only information about the genetic variations and mutations found in the Malays. In the near future, it will expand for the other Malaysian ethnics as well. The data sets are specified based on diseases or genetic mutation types which have three main subcategories: Single Nucleotide Polymorphism (SNP), Copy Number Variation (CNV) followed by the mutations which code for the common diseases among Malaysians. MyHVPDb has been open to the local researchers, academicians and students through the registration at the portal of MyHVP ( http://hvpmalaysia.kk.usm.my/mhgvc/index.php?id=register ). This database would be useful for clinicians and researchers who are interested in doing a study on genomics population and genetic diseases in order to obtain up-to-date and accurate information regarding the population-specific variations and also useful for those in countries with similar ethnic background.

Red blood cell (RBC) parameters obtained from hematology analyser has been very useful as the first line screening for thalassaemia. The changes are prominent in most type of β-thalassaemia but milder in α-thalassaemia. RBC parameters could have been normalized especially during pregnancy and in such situation screening these patients would require a different protocol. Blood samples from two hundred (200) Malay pregnant women attended obstetric clinic at Hospital Universiti Sains Malaysia (HUSM) were collected to screen for double α-gene deletion (-SEA, and –THAI), and the two single α-globin gene deletion (–α3.7 and -α4.2). Standard hematological analyses including red blood cell count and indices, and hemoglobin quantitation were performed on the blood samples. Of these, sixteen were excluded as they had HbA2 levels more than 4% and were diagnosed as HbE or β-thalassaemia trait. Then, multiplex GAP polymerase chain reaction (PCR) analyses of α-globin gene were performed on the remaining 184 blood samples. Total of 17 from 184 subjects confirmed to have α-thalassaemia (-α3.7/αα and --SEA/ αα genotype). The RBC indices were compared between those with α-thalassaemia and normal pregnant women and they were significantly different. -α3.7 kb single gene deletion (8.1%) was the commonest type followed by double gene South East Asia (--SEA) deletion (1.1%). We conclude that mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) with the cut off value of less than 86.3fl and 27.4 pg respectively are two useful RBC indices which can be used for screening of α-thalassaemia in pregnant women.