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This article discusses the presence of mild bleeding symptoms in individuals with severe hemophilia A and thalassemia disease. It is noted that a small percentage of individuals with severe hemophilia A experience mild bleeding symptoms, and half of them have prothrombotic gene mutations. Thalassemia disease, a type of anemia, has also been linked to a hypercoagulable state. The article presents a case study of a child with both thalassemia and mild hemophilia A, highlighting their bleeding symptoms and the use of genetic testing to identify gene abnormalities. The study found that the hypercoagulable state in thalassemia reduced bleeding in hemophilia A, and that red blood cell transfusions corrected anemia and reduced the hypercoagulable state in thalassemia patients. The study also identified a mutation in a specific gene that explained the patient's low factor VIII activity. Overall, the study suggests that thrombin generation assays can be useful in guiding treatment for individuals with thalassemia and hemophilia A. [Extracted from the article]

Background and Aims: Knee support, frequently made from sponge, is used to reduce injury. Sponge has less elasticity and durability compared with natural rubber. To our knowledge, there was no study that demonstrated the effectiveness of natural rubber and sponge in prevention of injury in children with bleeding disorders. The study aimed to demonstrate the effectiveness and satisfaction of natural rubber knee support compared with sponge knee support among children with bleeding disorders. Methods: The study consisted of three phases: (I) measuring reduced compression force, (II) producing size‐appropriate knee support prototypes, and (III) conducting a randomized crossover trial, including 8 weeks wearing natural rubber knee support and sponge knee support with a 4‐week wash‐out period. The number of knee bleeds and user satisfaction were recorded. Results: A better compression force reduction in natural rubber (60%) than sponge (12%) was demonstrated. Knee support comprised a body part, made from natural‐stretchable cotton and a protection part, made from either natural rubber or sponge. They were produced in four sizes: S, M, L, and XL and appropriately applied to 42 patients (21 hemophilia, 21 platelet disorders) with a mean (SD) age of 7.0 (2.9) years. The results from randomization showed no significant difference in the number of knee bleeds between the two knee support groups (10 vs. 7, p = 0.37). In terms of satisfaction score, the natural rubber knee supports were more durable (45.2% vs. 23.8%, p = 0.04) and easier to use (28.5% vs. 14.3%, p = 0.03). In addition, a higher percentage of parents chose natural rubber knee support when compared with sponge knee supports (71.0% vs. 29.0%, p = 0.006). Conclusion: Natural rubber knee support showed comparable effectiveness in the prevention of knee bleeding but was superior to sponge knee support in compression force reduction and satisfaction. [ABSTRACT FROM AUTHOR]

Introduction: Hereditary pyropoikilocytosis (HPP) is the most common cause of non‐thalassemic severe inherited hemolytic anemia in Thai population. Up to 90% of affected patients harbor biallelic mutations of SPTB Providence (SPTB c.6055T>C), SPTB Buffalo (SPTB c.6074T>G), and SPTB Chiang Mai (SPTB c.6224A>G). This study aimed to develop a simple assay for mass screening of the three common SPTB mutations and to study their carrier frequencies in a healthy Thai population. Methods: We combined multiplex amplification refractory mutation system‐PCR (ARMS‐PCR) and high‐resolution melting (HRM) curve analysis to create a one‐step single‐tube assay. The primers were designed to generate products with different melting temperatures in the presence of 6055C, 6074G, and 6224G. Internal control primers were added for quality control. Residual samples from blood donors and healthy adolescents were collected and tested for the three common SPTB mutations using the newly developed assay. Results: Optimized multiplex ARMS‐PCR/HRM curve assay yielded well‐separated melt curves to detect the three SPTB mutations with 4‐h turnaround time. The assay was validated in screening of 2261 non‐repetitive blood donors and 89 adolescents, in which 10 (0.43%), 2 (0.09%), and 3 (0.13%) individuals were identified as carriers of SPTB Providence, SPTB Buffalo, and SPTB Chiang Mai, respectively. All mutated SPTB and 20 random wild‐type samples were confirmed using Sanger sequencing with 100% accuracy. Conclusion: The novel ARMS‐PCR/HRM curve assay is simple, accurate, and time‐effective for mass screening of the common SPTB mutations. This can be employed to prevent HPP birth in a Thai population. [ABSTRACT FROM AUTHOR]

This article discusses the transfer of data from the Thai haemophilia treatment center registry to the Annual Global Survey (AGS) of the World Federation of Hemophilia (WFH). The data collection aims to improve care for patients with hereditary bleeding disorders by identifying available treatment resources, evaluating their effectiveness, and advocating for better care. The Thai Society of Haematology (TSH) initiated the Haemostasis Registry, which includes the Hereditary Bleeding Disorders Registry (HBDR) and Thrombosis. The data from the HBDR is transferred to the World Bleeding Disorders Registry (WBDR) and the AGS of the WFH. This data transfer reduces redundancy and improves the reliability, accuracy, cost-effectiveness, and efficiency of data collection. The article highlights the importance of the AGS in collecting data on patients with hereditary bleeding disorders and the treatments used worldwide. The data collected through the AGS is used for resource planning, advocacy, research, and development activities to improve the management of patients with these disorders. The authors emphasize the need for collaboration between clinicians and information technology personnel to ensure accurate data input and output. The dataset of the World Bleeding Disorders Registry and the questionnaire of the AGS are recommended as useful templates for data collection and reporting. The study was conducted ethically and the data is available upon request. [Extracted from the article]

Objectives: Patients with high‐risk hematologic diseases require intensive modalities, including high‐dose chemotherapy and allogeneic hematopoietic stem cell transplantation (allo‐HSCT). Haploidentical T‐cell–replete transplantation is a logical choice because of the limited availability of matched sibling donors and the prolonged time needed to identify matched unrelated donors in Thailand. Methods: The clinical outcomes data of 43 patients undergoing allo‐HSCT were reviewed. All patients had high‐risk hematologic malignancies, were younger than 20 years, and were in complete cytological remission at the time of allo‐HSCT. We used two different conditioning regimens: total body irradiation (TBI) combined with cyclophosphamide, fludarabine, and melphalan (n = 23) and thiotepa combined with fludarabine and busulfan (n = 20). All patients received a graft‐versus‐host disease prophylaxis regimen consisting of cyclophosphamide, mycophenolate mofetil, and a calcineurin inhibitor or sirolimus. Results: There was no difference in engraftment between patients receiving either of the regimens. After a median follow‐up of 35.8 (range, 0.6–106.2) months, the overall survival (OS) and event‐free survival (EFS) rates were 62.4% and 54.7%, respectively. OS and EFS were comparable between the respective regimens. Conclusions: We conclude that thiotepa‐based conditioning has similar efficacy and tolerability as TBI‐based conditioning for haploidentical HSCT with post‐transplant cyclophosphamide. [ABSTRACT FROM AUTHOR]

Effectiveness of monthly low dose emicizumab prophylaxis without 4-week loading doses among patients with haemophilia A with and without inhibitors: A case series report In conclusion, the monthly low-dose emicizumab prophylaxis of the whole vial at 1.05-1.66 mg/kg without loading dose showed effectiveness among patients with haemophilia A with and without inhibitor. Keywords: emicizumab; haemophilia A; inhibitor; loading dose; low dose EN emicizumab haemophilia A inhibitor loading dose low dose 382 385 4 01/27/23 20230101 NES 230101 Prophylaxis among patients with severe haemophilia A has clear efficacy to prevent bleeding episodes and subsequent sequelae of muscles and joints. Despite no patient included in this study reporting a zero annual bleeding rate, two of six included patients did achieve zero annual joint bleeding (33.3%). [Extracted from the article]

Background: Hemoglobin (Hb) H is generally recognized as mild thalassemia, despite its actual phenotypic diversity. A disease severity scoring system to guide initiation of regular transfusion among severely affected pediatric patients has not previously been reported. Methods: Patients with HbH were classified into transfusion‐dependent thalassemia (TDT) and non‐transfusion‐dependent thalassemia (NTDT) as a surrogate for disease severity. Alpha‐globin genotypes and relevant clinical parameters associated with TDT were identified. Univariate and multiple logistic regression analyses were performed to yield the most suitable severity scoring system. Results: From 246 patients with a median age of 14.3 (interquartile range 9.9–18.4) years initially enrolled into the study, the chance of having severe disease and developing TDT was remarkable only among patients with non‐deletional HbH, for whom the scoring system was developed. Univariate and multiple logistic regression analyses resulted in three retained parameters associated with TDT, β‐coefficients of which were used to develop the score. The final scoring system comprised age at diagnosis <2 years (score = 1), spleen size ≥3 cm (score = 1) and Hb at steady‐state <7 (score = 4) or 7–8 g/dL (score = 3). A cutoff score ≥4 was associated with severe disease likely requiring regular transfusion (sensitivity 89.3%, specificity 81.4%), given regular transfusion resulted in maintained growth. The scoring system was validated in the second cohort of 77 non‐deletional HbH, from which comparable sensitivity and specificity were obtained. Conclusion: The newly developed scoring system was practical and helpful to highlight severely affected pediatric non‐deletional HbH patients with potential needs of regular transfusion. This can be used as a guide for optimal treatment and disease monitoring in the future. [ABSTRACT FROM AUTHOR]

Summary: Next‐generation sequencing has shed light on the diagnosis of previously unsolved cases of inherited haemolytic anaemia (IHA). We employed whole‐exome sequencing to explore the molecular diagnostic spectrum of 21 unrelated Thai paediatric patients with non‐thalassemic IHA, presenting hydrops fetalis and/or becoming transfusion‐dependent for 1 year or more or throughout their lifespan. Anaemia was detected prenatally, within the first month and the fifth year of life in three, 12 and six patients respectively. Molecular diagnosis obtained from all patients revealed SPTB as the most frequently mutated gene (four reported, three novel), found in 31 of 42 studied alleles. The other two mutated genes identified were ANK1 (three novel) and KLF1 (two reported). Four recurring mutations within exon 29/30 (NM_001024858.2) accounted for the vast majority (90%) of mutated SPTB alleles, biallelic inheritance of which resulted in the most severe phenotypes: hydrops fetalis and life‐long transfusion dependency. Dominant ANK1 (n = 3) and SPTB (n = 2) mutations and biallelic class 2 KLF1 mutations (n = 1) led to a shorter period of transfusion dependency. Our study demonstrated that mutated SPTB causing red‐cell membranopathy is likely the most common cause of severe non‐thalassemic IHA among Thai patients. This urges carrier screening in the population to prevent subsequent, severely affected births. [ABSTRACT FROM AUTHOR]

Aims: The purpose of this study was to design and manufacture CD19 chimeric antigen receptor (CAR)‐modified T cells for clinical use in Thailand, as a model for how this technology can be directly applied at individual institutions treating high‐risk leukemia patients. Methods: We constructed second‐generation CAR T cells expressing CD19 scFV‐CD28‐CD3ζ with different lengths of the spacer region: full, intermediate, and short length, by using a lentiviral vector. We wanted to determine whether the difference in length of the spacer would affect the cytotoxic potential of the CD19 CAR T cells against the leukemic cells. Results: We found that all constructs of CD19 CAR T cells exhibited a similar level of cytotoxicity against several human lymphoma and leukemia cell lines. For the clinical application, we chose the intermediate length spacer construct CD19 CAR T cells, hypothesizing that the highest transduction efficiency coupled with a slower initial proliferation in vitro might lead to effective leukemic cell kill, yet a lower probability for serious clinical side effects. We then tested the clinical efficacy of our CD19 CAR T cells in one patient with refractory/relapsed acute B‐cell lymphoblastic leukemia. This patient indeed had minimal clinical side effects after the CAR T‐cell infusion, and he remains in an unmaintained, ongoing complete remission 10+ months after his T‐cell treatment. Conclusion: Our CD19 CAR T cells demonstrated efficacies in acute lymphoblastic B‐cell leukemia, and will be used to establish an immunotherapeutic program for high‐risk B‐cell acute lymphoblastic leukemia in Thailand. We propose that this approach can be used as a model for how this new exciting technology can be applied directly at individual institutions that treat (a large number of) patients with high‐risk leukemia. [ABSTRACT FROM AUTHOR]

To transfer selected data from the HBDR to the WBDR, two query screens were added for each user at the HBDR to complete. 1 TABLEData transferred from HBDR to WBDR HT