Search

Ampaiwan Chuansumrit,1 Rungrote Natesirinilkul,2 Nongnuch Sirachainan,1 Praguywan Kadegasem,1 Pacharapan Surapolchai,3 Noppawan Tangbubpha,1 Ketsuda Kempka,1 Tanyanee Khlangtan1 1Department of Pediatrics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; 2Department of Pediatrics, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; 3Department of Pediatrics, Faculty of Medicine, Thammasat University, Pathum Thani, ThailandCorrespondence: Ampaiwan Chuansumrit, Department of Pediatrics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, 270 Rama VI Road, Rachathewi District, Bangkok, 10400, Thailand, Tel +66 2 2011749, Fax +66 2 2011748, Email ampaiwan.jua@mahidol.ac.thBackground: Hemophilia cannot be diagnosed in most laboratories of economically less-developed countries leading to high mortality and morbidity rates.Aim: A diagnostic tool was established ranging from bleeding assessment and a simple bedside test of mixing venous clotting time (VCT) to comprehensive DNA analysis for patients with hemophilia.Methods: Patients with known (n=80) and suspected hemophilia (n=14) were included. Their bleeding symptoms were initially evaluated using verified translated-Thai ISTH bleeding assessment tool. Then, blood samples were drawn using a two-syringe technique, 2 mL each was placed in three tubes, for the mixing VCT and citrate blood was kept for coagulogram and coagulation factor assay. Finally, DNA analysis was determined.Results: A total of 94 patients with hemophilia (A68, B26) defined as severe (A 57, B 17), moderate (A 7, B 5), and mild degrees (A 4, B 4) with the mean (SD) age of 14.0 (11.7) years and 24 normal controls aged 25.5 (4.5), were enrolled in the study. The mean (SD) bleeding score of patients with hemophilia was 13.5 (5.5), which did not significantly differ between patients with hemophilia A and B. The mixing venous clotting time offered the presumptive diagnosis of hemophilia A and B, which were subsequently confirmed by the prolonged APTT, low FVIII:C and FIX:C and mutations on the factor VIII and IX genes.Conclusion: A diagnostic tool for bleeding assessment, mixing venous clotting time, coagulogram, coagulation factor assay, and DNA analysis for patients with hemophilia has been established in the existing health-care system.Keywords: diagnostic tool, hemophilia A & B, bleeding score, mixing VCT, F8 & F9 gene mutation

Ampaiwan Chuansumrit,1 Werasak Sasanakul,1 Nongnuch Sirachainan,1 Suttikarn Santiwatana,1 Praguywan Kadegasem,1 Pakawan Wongwerawattanakoon,2 Noppawan Tungbubpha,1 Juthamard Chantaraamporn1 1Department of Pediatrics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; 2Department of Nursing, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, ThailandCorrespondence: Ampaiwan Chuansumrit, Department of Pediatrics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, 10400, Thailand, Tel +66 2 2011749, Fax +66 2 2011748, Email ampaiwan.jua@mahidol.ac.thObjective: The study aimed to report a 3-decade successive establishment of care for women/girls from families with haemophilia.Methods: A retrospective analysis was conducted on 462 women/girls from 243 families from 1987 to 2021.Results: Combining phenotypic analysis of coagulation factor and genotypic analysis of either linkage analysis or mutation detection confirmed the status of all obligate haemophilia carriers (A118, B19). For potential carrier, 159 proven carriers (A130, B29) and 146 noncarrier status (A126, B20) were diagnosed except 20 potential carriers (A16, B4). Only 54 prenatal diagnoses were requested resulting in normal males (n = 21), males with haemophilia A (n = 12) and females with either normal or carrier status (n = 21). Additionally, 40 women/girls with haemophilia carrier received a diagnosis of severe haemophilia A with Turner’s syndrome (n = 2) and mild haemophilia (A31, B7). The skewed X-chromosome inactivation of the nonmutant factor VIII/IX carrying X-chromosome of 8% (2/25) was found in mild haemophilia. Factor concentrate and desmopressin are prescribed for these affected women/girls. The response of women/girls with either haemophilia carrier or haemophilia was amazement with their religious beliefs and cultural acceptance.Conclusion: Appropriate care for women/girls from families with haemophilia concerning diagnosis and management of haemophilia and carrier has been successively established.Keywords: women and girls, families with haemophilia, haemophilia carrier, severe haemophilia, mild haemophilia

Werasak Sasanakul, Ampaiwan Chuansumrit, Nongnuch Sirachainan, Praguywan Kadegasem Department of Pediatrics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, ThailandCorrespondence: Ampaiwan Chuansumrit, Department of Pediatrics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, 10400, Thailand, Tel +66 2 2011749, Fax +66 2 2011748, Email ampaiwan.jua@mahidol.ac.thBackground: Adequate replacement for patients with hemophilia is costly, especially in countries with limited resources.Objective: Factor VIII gene mutations among Thai patients with hemophilia A were analyzed for the most common mutation. The cost-effectiveness of finding one female without family history of hemophilia possessing the most common factor VIII mutation was compared with the cost of treating one patient with hemophilia.Methods: In all, 109 unrelated patients with hemophilia A, defined as sporadic cases (n=58) and hereditary cases (n=51), were enrolled for genotypic analysis.Results: Intron 22 inversion was prominently found in 34 sporadic (58.6%) and 27 hereditary (51.9%) cases. The screening for intron 22 inversion among females without family history of hemophilia at antenatal care has been optionally suggested. A female with a positive result will undergo further prenatal diagnosis of hemophilia in her male offspring. On the contrary, a female with a negative test result remains at risk to have a hemophiliac son caused by other factor VIII gene mutations not included in the screening but the risk is not as high as intron 22 inversion. Although the screening of factor VIII mutation among females without family history of hemophilia is against the current practice, it has been initiated due to the inadequate treatment provided to patients with hemophilia in countries with limited resources. The study calculated approximately one female with intron 22 inversion would exist among 17,064 females without family history of hemophilia. The cost of screening (194,870 USD) was much less than that of treating one patient with hemophilia from birth to 40 years of age by the current regimen (378,000 USD).Conclusion: Implementing antenatal screening of intron 22 inversion among females without family history of hemophilia is optionally suggested, especially in economically less-developed countries with inadequate treatment service for patients with hemophilia.Keywords: intron 22 inversion, sporadic, hemophilia, hemophilia A, antenatal screening, female, cost-effectiveness

Objective: The phenotypic and genotypic analysis of patients with congenital factor VII deficiency were retrospectively conducted. Methods: The study included 26 patients defined as severe (n = 25) and moderate (n = 1) degree by FVII 3% did not exhibit serious spontaneous bleeding. The initial bleeding episodes were controlled by administering fresh frozen plasma (FFP) and switched to factor concentrates among a few patients upon definite diagnosis. Subsequent prophylaxis was provided to patients with initial severe bleeding manifestation using FFP (15 ml/kg) 2–3 times weekly or recombinant factor VIIa (90 μg/kg) twice weekly. Genotypic analysis revealed homozygous or double heterozygous mutations among all patients except one patient with heterozygous mutation combined with homozygous polymorphism at codon 413 of G to A substitution (AA) at exon 8 of the FVII gene. The FVII gene mutation was commonly found at IVS6+1G > T (38.3%), followed by p.K376 X (19.2%) and IVS2+2T > C (17.0%). The case fatality rate was 19.2% (5/26) among patients with severe degree. Conclusion: Early diagnosis and appropriate management of congenital factor VII deficiency is essential for favorable outcomes.

Background: Closure time (CT), a parameter measured by platelet function analyzer (PFA-100), is used to assess primary hemostasis. However, some factors (e.g., ethnicity and age) may affect its cut-off value or reference range. Moreover, the diagnostic performance of CT in the Thai and Southeast Asian populations has not been reported in any study. Therefore, this study aims to evaluate the diagnostic performance of CT in patients with mucocutaneous bleeding disorder using the established cut-off value from Thai children. Methods: CT from both collagen/epinephrine (COL/EPI) and collagen/adenosine 5- diphosphate (COL/ADP) cartridges and complete blood count were performed in both healthy volunteers and known cases of primary hemostatic disorders. The cut-off value and diagnostic performance of CT was determined using receiver operating characteristic curve analysis. Results: The cut-off value of both COL/EPI and COL/ADP in this study was somewhat prolonged than the other studies because of the higher prevalence of non-responsiveness of platelets to epinephrine stimulation in the Asian than the Western. Nonetheless, the diagnostic performance was comparable to the previous studies. In addition, the diagnostic performance could be enhanced when the CT from both cartridges was interpreted together. Conclusion: The cut-off value in this study was more prolonged than in other studies due to the variation of ethnicity. Consequently, each laboratory should establish and/or verify its own CT reference range prior to use in clinical practice. Furthermore, CT interpretation of both cartridges together resulted in a better diagnostic performance than interpreting each cartridge separately.

Abstract Background/Objective We report the first analysis of an extended half‐life recombinant factor IX, nonacog beta pegol (N9‐GP), in previously untreated patients (PUPs) and minimally treated patients with hemophilia B. Methods Paradigm 6 (Safety and Efficacy of Nonacog Beta Pegol [N9‐GP] in Previously Untreated Patients With Haemophilia B) is a multicenter, open‐label, single‐arm, phase 3 trial. Main inclusion criteria were males aged

Antiphospholipid antibodies (APAs) are developed antibodies to the phospholipid surfaces or to the proteins binding to phospholipids. Increased PS-expressed red blood cells (RBC) may be a risk factor in APAs development. There were only a few studies reported on APAs in thalassemia, and their associations to PS-expressing microparticles (MPs), remain unknown. The presence of antiphospholipid antibodies (APAs) in pediatric thalassemia patients and their associations with phosphatidylserine (PS)- expressing microparticles (MPs), a previously unexplored relationship, were the aims of this report. We identified that positive APA rates were highest in non-transfusion-dependent thalassemia (NTDT) subjects, followed by transfusion-dependent thalassemia (TDT) subjects and controls (29.5%, 18.2% and 17.9%, respectively). Subgroup analysis demonstrated that positive anti- ?2 glycoprotein I (a?2-GPI)- IgG rates in NTDT subjects were significantly greater than in controls and that the percentage of MPs was also significantly elevated in thalassemia subjects. More specifically, there were significant correlations found between a?2GPI-IgG and anticardiolipin (aCL)-IgM APAs, and MPs.

The study aimed to determine efficacy and safety of generic deferasirox monotherapy. Deferasirox was administered in transfusion-induced iron overloaded thalassemia. Efficacy was defined as responders and nonresponders by ≤ 15 reduced serum ferritin from baseline. Adverse events were also monitored. Fifty-two patients with mainly Hb E/β-thalassemia at the mean (SD) age of 8.7 (4.1) years, were enrolled. The mean (SD) daily transfusion iron load was 0.47 (0.1) mg/kg and maximum daily deferasirox was 35.0 (6.2) mg/kg. Altogether, 52, 40 and 18 patients completed the first, second and third years of study, respectively. The median baseline serum ferritin 2,383 ng/mL decreased to 1,478, 1,038 and 1,268 ng/mL at the end of first, second and third years, respectively, with overall response rate at 73.1% (38/52). Patients with baseline serum ferritin >2,500 ng/mL showed a change in serum ferritin higher than those ≤2,500 ng/mL starting from the 9th month of chelation. Adverse events were found in 5 of 52 patients (9.6%) including transaminitis (n = 2), one each of proteinuria, rash and proximal tubular dysfunction which resolved after transient stopping or decreasing the chelation dose. Generic deferasirox was effective and safe among pediatric patients with transfusion-induced iron overloaded thalassemia. [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]

Human mesenchymal stem cells (hMSCs) have the potential to differentiate into hepatocyte-like cells, indicating that these cells may be the new target cell of interest to produce biopharmaceuticals. Our group recently established a hMSC-derived immortalized hepatocyte-like cell line (imHC) that demonstrates several liver-specific phenotypes. However, the ability of imHC to produce coagulation factors has not been characterized. Here, we examined the potential for imHC as a source of coagulation protein production by investigating the ability of imHC to produce human factor VII (FVII) using a lentiviral transduction system. Our results showed that imHC secreted a low amount of FVII (~22 ng/mL) into culture supernatant. Moreover, FVII from the transduced imHC (0.11 ± 0.005 IU/mL) demonstrated a similar coagulant activity compared with FVII from transduced HEK293T cells (0.12 ± 0.004 IU/mL) as determined by chromogenic assay. We demonstrate for the first time, to the best of our knowledge, that imHC produced FVII, albeit at a low level, indicating the unique characteristic of hepatocytes. Our study suggests the possibility of using imHC for the production of coagulation proteins.