Jameela Sathar

Introduction: National registries are essential infrastructure for haemophilia and allied bleeding disorders, but registry development and international alignment across the Asia–Pacific region remain unclear. Aim: To evaluate the availability, governance, technical infrastructure, international engagement, and patient‐facing digital functions of national haemophilia registries across the Asia–Pacific region. Methods: The AHAD‐AP Registry Committee conducted a structured survey of Country/Region/Territory (CRT) representatives. The questionnaire assessed registry status, funding and governance, international alignment, technical infrastructure, data‐entry methods, and digital functions. Multiple responses from the same CRT were harmonized when needed. Results: Nineteen individual responses representing 15 CRTs were consolidated into 15 CRT‐level responses. Ten CRTs reported an active national registry, one a planned registry, three no national registry, of which two had centres participating in World Bleeding Disorders Registry (WBDR), and one hospital‐based registry. Haemophilia was included in all, while VWD and other inherited coagulation factor deficiencies were included in 11 of 12. Mandatory registration was reported by 5 CRTs. Funding and governance structures varied across CRTs. Awareness of WBDR was reported by 12 of 15 CRTs, while dataset alignment, data submission, and technical integration were reported by 8, 4, and 1 CRTs, respectively. Manual data entry remained common (9/12), and patient‐oriented digital functions, including infusion logs or related support tools, were reported by 10 of 12 registries. Conclusion: This survey represents the first large regional assessments of national haemophilia registry infrastructure across the Asia–Pacific region. Harmonized datasets, sustainable governance, technical integration, and patient‐facing digital tools may support future registry development.

Characterising genomic variants is paramount in understanding the pathogenesis and heterogeneity of normal-karyotype acute myeloid leukaemia (AML-NK). In this study, clinically significant genomic biomarkers were ascertained using targeted DNA sequencing and RNA sequencing on eight AML-NK patients’ samples collected at disease presentation and after complete remission. In silico and Sanger sequencing validations were performed to validate variants of interest, and they were followed by the performance of functional and pathway enrichment analyses for overrepresentation analysis of genes with somatic variants. Somatic variants involving 26 genes were identified and classified as follows: 18/42 (42.9%) as pathogenic, 4/42 (9.5%) as likely pathogenic, 4/42 (9.5%) as variants of unknown significance, 7/42 (16.7%) as likely benign and 9/42 (21.4%) as benign. Nine novel somatic variants were discovered, of which three were likely pathogenic, in the CEBPA gene with significant association with its upregulation. Transcription misregulation in cancer tops the affected pathways involving upstream genes (CEBPA and RUNX1) that were deregulated in most patients during disease presentation and were closely related to the most enriched molecular function gene ontology category, DNA-binding transcription activator activity RNA polymerase II-specific (GO:0001228). In summary, this study elucidated putative variants and their gene expression profiles along with functional and pathway enrichment in AML-NK patients.

Background: Perioperative anemia has been associated with increased risk of red blood cell transfusion and increased morbidity and mortality after surgery. The optimal approach to the diagnosis and management of perioperative anemia is not fully established. Objective: To develop consensus recommendations for anemia management in surgical patients. Methods: An international expert panel reviewed the current evidence and developed recommendations using modified RAND Delphi methodology. Results: The panel recommends that all patients except those undergoing minor procedures be screened for anemia before surgery. Appropriate therapy for anemia should be guided by an accurate diagnosis of the etiology. The need to proceed with surgery in some patients with anemia is expected to persist. However, early identification and effective treatment of anemia has the potential to reduce the risks associated with surgery and improve clinical outcomes. As with preoperative anemia, postoperative anemia should be treated in the perioperative period. Conclusions: Early identification and effective treatment of anemia has the potential to improve clinical outcomes in surgical patients.

Background: Thalassemia is a genetic blood disorder characterized by insufficient haemoglobin level due to mutation in the globin chains causing anaemia with iron overload and the most common genetic haemoglobinopathy in Malaysia. They are grouped as transfusion dependent and non-dependent according to their transfusion requirement. The frequency of thalassemia transfusions can be discriminated further into monthly to non-monthly transfusion group. Objective: To analyze the socio-demographic characteristic, haemoglobin levels and BMI distribution after classifying the thalassemia patients according to monthly transfused group (MTG), non-monthly transfused group (NMTG) and comparing to a healthy individual control group. Methods and Materials: This was a prospective cross-sectional study gathering data on socio-demographic characteristic, haemoglobin levels and BMI distribution of patients with MTG and NMTG thalassemia patients from a thalassemia clinic in Ampang Hospital and comparing them to healthy individuals in Faculty of Medicine and Health Sciences, Universiti Putra Malaysia. The study embarked between August to October 2020. Results: Our study clearly shows in adult thalassemia MTG are predominantly in Malay ethnicity and younger in comparison to NMTG. The mean Hb levels of MTG is lower compared to NMTG regardless of the genotype and phenotype characteristics.

Hitherto, no data describing the heterogeneity of genetic profiles and risk stratifications of adult acute myeloid leukaemia (AML) in Southeast Asia are reported. This study assessed genetic profiles, Moorman’s hierarchical classification, and ELN 2017-based risk stratifications in relation to age, gender, and ethnicity in Malaysian adult AML patients. A total of 854 AML patients: male (52%), female (48%) were recruited comprising three main ethnic groups: Malays (59%), Chinese (32%) and Indians (8%). Of 307 patients with abnormal karyotypes: 36% exhibited translocations; 10% deletions and 5% trisomies. The commonest genotype was FLT3-ITD-NPM1wt (276/414; 66.7%). ELN 2017 risk stratification was performed on 494 patients, and 41% were classified as favourable, 39% as intermediate and 20% as adverse groups. More females (47%) were in the favourable risk group compared to males (37%), whereas adverse risk was higher in patients above 60 (24%) of age compared to below 60 (18%) patients. We observed heterogeneity in the distribution of genetic profiles and risk stratifications between the age groups and gender, but not among the ethnic groups. Our study elucidated the diversity of adult AML genetic profiles between Southeast Asians and other regions worldwide.

There have been various Haemophilia Treatment Centres (HTCs) set up worldwide with innovative blood factor stewardship programs. Pharmacists have been an extended part of stewardship programs providing daily rounds with haematologists, treatment plan modifications, and dosage adjustment recommendations. The Haemophilia Treatment Centres in Malaysia contain the Haemophilia Medication Therapy Adherence Clinic (HMTAC), which recruits adolescent and adult populations. There have not been any adherence studies conducted on pharmacist-steered HMTAC since initiation. The current research generates baseline data to produce treatment plans and intervention measures needed for therapy optimisation in the Malaysian population. This study also explores the relationship between medication adherence, bleeding rate, and comorbidity. This cross-sectional study involved retrospective and prospective data collection using the Validated Haemophilia Regimen Treatment Adherence Scale–Prophylaxis (VERITAS-Pro) in Ampang Hospital. The retrospective data collection included reviewing patients’ medical records, bleeding diaries, and VERITAS-Pro questionnaires pre-enrolment to HMTAC. Meanwhile, the prospective data collection was the VERITAS-Pro questionnaire administration post a minimum of three months after enrolment. The inclusion criteria were patients with severe haemophilia A and B with ages ≥18 years with self-administered prophylactic regimens for a minimum period of three months. There were six (5.8%) nonadherent participants, and 97 (94.2%) adhered to the preventive treatment. The subscale dosing and remembering and the total score of the VERITAS-Pro post-HMTAC showed a significant association with ABR. There was a significant mean reduction in the post-HMTAC compared to the pre-HMTAC score for the total score and subscales timing, remembering, skipping, and communicating. There was a significant association between the post-HMTAC adherence status and ABR. It can be concluded that the HMTAC service pioneered by the pharmacists in the National Referral Centre of Haematology is efficient in significantly improving the VERITAS-Pro scoring and then translating it into a high medication adherence rate. This study also highlights a significant correlation between post-HMTAC scores on their adherence with ABR and comorbidities.

Background Prognostication of myeloproliferative neoplasm (MPN) has always been challenging, even with the advent of Janus kinase 2 (JAK2 V617F) molecular studies. The survival pattern of patients diagnosed with MPN in developing countries is still undetermined. Materials and methods The national MPN registry conducted from 2009 to 2015 in Malaysia provided a comprehensive insight into the demographics, clinical characteristics and laboratory parameters of patients diagnosed with MPN nationwide. The study analysed the survival patterns and mortality outcomes and risk among 671 patients diagnosed with essential thrombocythaemia (ET), polycythaemia vera (PV), primary myelofibrosis (PMF) and unclassified MPN (MPN-U). Mortality status was traced and confirmed until the end of December 2018, with right censoring applied to patients alive beyond that. Results The analysed cohort consisted of 283 (42.2%) ET, 269 (40.1%) PV, 62 (9.2%) PMF and 57 (8.5%) MPN-U incident cases with diagnosis made between 2007 and 2015. The majority of patients were male (52.3%) and Malay (48.9%), except for ET, in which the majority of patients were female (60.1%) and of Chinese origin (47.0%). Female patients were found to have significantly better overall survival (OS) rates in ET (p = 0.0285) and MPN-U (p = 0.0070). Patients with JAK2 V617F mutation were found to have marginally inferior OS over time. Multivariable Cox regression identified patients with increased age [hazard ratio (HR) 1.055, 95% CI 1.031; 1.064], reduced haemoglobin (HB) level (HR 0.886, 95% CI 0.831; 0.945, p = 0.0002), being male (HR 1.545, 95% CI 1.077; 2.217, p = 0.0182), and having MPN-U (HR 2.383, 95% CI 1.261; 4.503, p = 0.0075) and PMF (HR 1.975, 95% CI 1.054; 3.701, p = 0.0335) at increased risk for worse mortality outcomes. Conclusion Myeloproliferative neoplasm reduces patient survival. The degree of impact on survival varies according to sub-type, sex, bone marrow fibrosis and HB levels. The JAK2 V617F mutation was not found to affect the survival pattern or mortality outcome significantly.

Thalassemia is one of the major inherited haematological disorders in the Southeast Asia region. This study explored the potential utility of red blood cell (RBC) parameters and reticulocyte cell population data (CPD) parameters in the differential diagnosis of α and β-thalassaemia traits as a rapid and cost-effective tool for screening of thalassemia traits. In this study, a total of 1597 subjects (1394 apparently healthy subjects, 155 subjects with α-thalassaemia trait, and 48 subjects with β-thalassaemia trait) were accrued. The parameters studied were the RBC parameters and reticulocyte CPD parameters derived from Unicel DxH800. A novel algorithm named αβ-algorithm was developed: (MN-LMALS-RET × RDW) − MCH) to discriminate α from β-thalassaemia trait with a cut-off value of 1742.5 [AUC = 0.966, sensitivity = 92%, specificity = 90%, 95% CI = 0.94–0.99]. Two prospective studies were carried: an in-house cohort to assess the specificity of this algorithm in 310 samples comprising various RBC disorders and in an interlaboratory cohort of 65 α-thalassemia trait, and 30 β-thalassaemia trait subjects to assess the reproducibility of the findings. We propose the αβ-algorithm to serve as a rapid, inexpensive surrogate evaluation tool of α and β-thalassaemia in the population screening of thalassemia traits in geographic regions with a high burden of these inherited blood disorders.

Hitherto, there has been no comprehensive study on the usefulness of cell population data (CPD) parameters as a screening tool in the discrimination of non-neoplastic and neoplastic haematological disorders. Hence, we aimed to develop an algorithm derived from CPD parameters to enable robust screening of neoplastic from non-neoplastic samples and subsequently to aid in differentiating various neoplastic haematological disorders. In this study, the CPD parameters from 245 subtypes of leukaemia and lymphoma were compared against 1103 non-neoplastic cases, and those CPD parameters that were vigorous discriminants were selected for algorithm development. We devised a novel algorithm: [(SD-V-NE*MN-UMALS-LY*SD-AL2-MO)/MN-C-NE] to distinguish neoplastic from non-neoplastic cases. Following that, the single parameter MN-AL2-NE was used as a discriminant to rule out reactive cases from neoplastic cases. We then assessed CPD parameters that were useful in delineating leukaemia subtypes as follows: AML (SD-MALS-NE and SD-UMALS-NE), APL (MN-V-NE and SD-V-MO), ALL (MN-MALS-NE and MN-LMALS-NE) and CLL (SD-C-MO). Prospective studies were carried out to validate the algorithm and single parameter, MN-AL2-NE. We propose these CPD parameter-based discriminant strategies to be adopted as an initial screening and flagging system in the preliminary evaluation of leukocyte morphology.

Nonadherence to iron chelation therapy (ICT) remains a long-standing and serious issue in thalassemia, especially in resource-constrained developing countries. Barriers and facilitators of adherence to ICT in transfusion-dependent thalassemia (TDT) adult patients in Malaysia are not completely understood. This qualitative study explored factors affecting adherence to ICT among TDT adult patients at a public tertiary hospital in Malaysia. Data were collected through 21 semistructured in-depth interviews conducted among purposively sampled patients using a pretested interview guide. All interviews were audio-recorded and transcribed verbatim. Data were analyzed manually using thematic analysis method and managed using Atlas.Ti software. The most frequently discussed subthemes of barriers to adherence included patient-related factors, medications-related factors, sociocultural-related factors, environmental context and resources, and patient–health care provider relationship factors. The facilitators to adherence included having insights of their illness, prevailing sources of motivation emphasizing on strong self-efficacy, low medication burden, and having enabling environment. This study has identified barriers and facilitators that are unique to Malaysian thalassemic adults related to medication adherence. Options for future multifaceted interventions are suggested.