METHODS: A total of 222 blood samples were collected from healthy, unrelated Malay, Chinese and Indian individuals. Their HNA-1, -3 and -4 and HNA-5 loci were genotyped using polymerase chain reaction-sequence specific primer (PCR-SSP) or PCR-restriction fragment length polymorphism (RFLP) assays.
RESULTS: All HNA loci are polymorphic, except for HNA -4. Geneotypes HNA-1a/1b, -3a/3b and -4a/4a were observed most frequently at these three loci in all three ethnic groups. In contrast, HNA-5a/5b and -5a/5a were observed as the predominant genotypes in Malays vs. Chinese and Indians, respectively. The Malays, Chinese and Indians shared HNA -3a (0.505-0.527), HNA -4a (1.000) and -5a (0.676-0.854) as the most frequent alleles. However, HNA-1a was found to be the most common in Malays (0.506) and Chinese (0.504) and HNA-1b for Indians (0.525).
CONCLUSION: Combined with HNA data that have been published for Malay subethnic and Orang Asli groups, this study provides the first fully comprehensive HNA dataset for populations to be found in Peninsular Malaysia. Overall, our findings provide further evidence of genetic complexity in the region. This now publicly available HNA dataset can be used as a reliable reference source for improving medical outcomes.
METHODOLOGY: A prospective single-center cohort study was conducted in a tertiary care set-up. Transfusion Dependent Thalassemia patients registered with the pediatric unit were screened for hypercoagulability using TEG during six months of the study period and followed up for three years for the development of thromboembolic events. Patient demographics, history of splenectomy, Serum ferritin levels and annual red cell transfusion requirement (mL/kg/year) were assessed. TEG parameters used were R time, K time, alpha angle, Maximum amplitude, Clot index, and Lysis 30. The thrombin generation test (V Curve) obtained from the first-degree derivate of the TEG velocity curve was also used for analysis.
RESULTS: A total of 34 patients were recruited during the six months study period with an average age of 10.6 years ( ± 5.47). The average pre-transfusion hemoglobin level and the volume of packed red cells received were 7.24 g/dL and 152.82 mL/kg/year respectively. The TEG tracing was suggestive of a hypercoagulable state in 58.82% of patients. The mean values of angle (70.74), MA (64.16), CI (2.65) and TG (774.43) in TDT patients compared to age matched reference range (62.81, 57.99, 0.8, 577.83 respectively) was suggestive of prothrombotic changes. Annual blood transfusion requirement was negatively correlated with hypercoagulable status (-0.344, CI= -0.68 to 0.08). One out of 34 patients developed corona radiata infarct (with annual blood requirement; 112.7 mL/kg/Year). The risk to develop a hypercoagulable state appeared to be higher when the volume of RBCs transfused was less than 154 mL/kg/Year.
CONCLUSION: TDT patients are at risk of developing thromboembolism, and screening with TEG may be useful to identify those at high risk.