Showing 20 results for Hemophilia
Morteza Karimipour, Sirous Zeinali, Edward Graham Tuddenham, Nafiseh Nafissi, Manijeh Lak, Peter Green,
Volume 1, Issue 2 (12-2009)
Abstract
Background: Heterogeneous mutations in the human coagulation factor IX gene lead to an X-linked recessive bleeding disorder known as hemophilia B. The disease is distributed worldwide with no ethnic or geographical priority.
Materials and Methods: The aim of this study was to characterize the factor IX gene mutations in 28 unrelated Iranian hemophilia B patients. Polymerase chain reaction (PCR) and direct sequencing was performed for all functionally important regions of the gene. Haplotype analysis was performed using three markers.
Results: We identified 24 point mutations and four small deletions (one novel mutation). Overall, 20 different mutations were found and patients with common mutations had identical haplotype.
Conclusion: These data confirm high molecular heterogeneity of the mutations causing hemophilia B and will enable carrier testing and prenatal diagnosis for family members.
Hassan Mansouri Torghabeh, Aliakbar Pourfathollah, Mahmoud Mahmoudian Shoushtari,
Volume 1, Issue 2 (12-2009)
Abstract
Background: Hemophilia B is a bleeding disorder with a recessive X-linked inheritance pattern, in which the infected individuals have low levels of factor IX in their plasma. Affected individuals may have bleeding episodes after trauma or spontaneously considering the plasma level of factor IX. In order to prevent these episodes and to control bleeding, they should use coagulation factor concentrates that may be associated with the formation of inhibitors.
Methods: This study was conducted in the northeast of Iran in 2006. Among 48 individuals who agreed to participate in our survey, 3 individuals (6.25%) had used FFP, 38 s (79.16%) factor IX concentrate and 7 (14.58 both FFP and factor IX concentrate in the 6 months prior to the study. Of them, three participants (6.3%) had factor IX inhibitor which was assayed using Bethesda method.
Results: Three hemophilia B (6.3%) patients had factor IX inhibitor, but no correlation was found between the existence of the inhibitor and the type of coagulation therapy.
Conclusion: Our findings did not show any correlation between factor IX inhibitor and type of coagulation therapy used in the 6 month period (p=0.65). None of the hemophiliacs had used coagulation factor as a prophylaxis regimen and most of them (83.33%) had injected coagulation factor on demand.
Volume 2, Issue 3 (5-2010)
Abstract
Background:Chronic synovitis is one of the most important complications in haemophilic patients. Rifampin is an
antibiotic which its intra-articular injecion leads to destruction of the synovial membrane of haemophilic patients
medically.
Materials and Methods: Between September 2003 and November 2005, we administered intra-articular rifampin
in ١۶ haemophilic joints of ٨ haemophilic patients.
Results:Median age of our patients was 14.5 year-old. There were 11 knee joints and 5 elbow joints. Atier treatment
we observed significant improvement in treated joints.
Conclusion:This study reveals that intra-articular injection of rifampin may improve arthropathy in haemophilic
patients.
Peyman Eshghi, Borhan Moradveisi,
Volume 4, Issue 1 (12-2011)
Abstract
This study was undertaken to assess the frequency of decreased bone mineral density and its risk factors as well as its impact on the quality of life during childhood among hemophiliac patients.
Materials and Methods: Thirty seven children with severe hemophilia A and B, referred to Mofid Children’s Hospital during 2010, were selected. For all patients the joint score, body mass indexes, bone mineral density, the level of inhibitor antibodies were measured. Short forms of Haeamo-QoL questionnaire were used to assess their quality of life. Data were statistically analyzed using Kolmogorov-Smirnov Z, Mann-Whitney, T-test, Fisher’s eact test, and χ² test.
Results: In this study the overall prevalence of low bone density was 35%. Factors that were significantly associated with the frequency and severity of decreased bone density were age, presence of inhibitor antibodies, and reduced joint range of motion. Total quality of life score, and the sub scores of “viewpoint” and “others” as well as the “attitude” were decreased significantly in patients with decreased bone density.
Conclusion: According to our findings there is a high prevalence of low bone density among hemophiliac patients. The body mass index should be maintained by appropriate nutrition and exercise to prevent loss of bone density in patients with hemophilia. Prophylaxis regimen in early childhood and regular monitoring of inhibitor antibody development are advised for early detection and management of this complication.
Key words: Hemophilia, antibody, body mass index, bone mineral density, quality of life
Mohsin Sh, Jaffar J, Hussain Sh, Suhail Sh, Ikram Ullah M, Amjad S,
Volume 4, Issue 4 (7-2012)
Abstract
Background: Factor VIII administration to hemophilia A patients results in an immune response (inhibitor formation)
which significantly complicates the therapy. The present study was performed to determine the prevalence of
inhibitor development in hemophilia A patients receiving recombinant factor VIII therapy.
Materials and Methods: This was an observational descriptive study. Clotting factor inhibitor screening was
performed by activated partial thromboplastin time mixing studies using normal pool plasma collected from twenty
healthy donors. Bethesda assay for quantitation of factor VIII inhibitors was performed on samples which were
positive with screening tests.
Results: Out of 229 patients with hemophilia A enrolled in the hemophilia society of Pakistan, Lahore center, 50
patients were selected. The mean factor VIII level in these patients was 2.46 +3.14. Out of 50 patients, 29 (58%)
had severe hemophilia A (factor VIII level <1%), 17 (34%) had moderate hemophilia A (factor VIII level 1-5%) and 4
(12%) had mild hemophilia A (factor VIII level >5-30%). In this study, 12 patients (24%) were positive for inhibitors.
Most of them 9 (75%) were low responders (<5 Bethesda units) with a mean Bethesda units of 1.82+0.473, while 3
(25%) patients were high responders (>5 Bethesda units) with a mean BU of 11.33+5.85. Patients were divided into
two groups on the basis of the number of factor VIII concentrate therapies of <50 (group 1) times and >50 times
(group 2). Inhibitor positivity was high (34.5%) in group I, as compared to group II (9.5%). Bleeding episodes were
also more common in inhibitors positive patients.
Conclusion: In this study, the inhibitor development in patients with hemophilia A receiving recombinant factor VIII
concentrates therapy was 24% and the first fifty therapies were crucial for inhibitor development.
Keywords: Hemophilia A, inhibitors, Bethesda units.
Eshghi P, Khanali L, Abed-Saeedi J, Farahani H, Abdolah Gorgi F, Habib- Panah B, Tehrani Tarighat S, Alavi S, Taslimi S,
Volume 5, Issue 2 (1-2013)
Abstract
Background: Treating a chronic disease such as hemophilia is to improve the symptoms and quality of life (QOL) of
the patients. This study aimed to study the quality of life among hemophilic children and compare the quality of life
between patients receiving prophylactic or on demand treatments.
Materials and Methods: In this descriptive-comparative study, we enrolled 60 patients from three main hemophilia
care centers in Tehran. All patients were 4-7 year old. Half of the patients were receiving prophylactic and half were
receiving on-demand treatment. The assessment tool was Heamo-QoL questionnaire which assesses the quality
of life in different dimensions (physical, feeling, family, friends, others, attitude, treatment and behavior). In this
instrument, higher points correspond to lower quality of life. The mean quality of life in each dimension and also the
total score were determined. Quality of life was compared between prophylactic and on demand treatments.
Results: The mean quality of life in groups receiving prophylactic and on-demand treatments were 2.6±0.3 and
3.33±0.4 respectively (P<0.001). All dimensions except “treatment” and “feeling” were different between groups. The
highest impairments among patients, regardless of their treatment regimen, were in family and physical dimensions.
Conclusion: It is necessary to pay more attention to prophylactic treatment in hemophilic children as it seems to
provide a higher quality of life among patients.
Keywords: Hemophilia, quality of life, prophylactic, treatment, on demand, Heamo-QoL.
Mostafa Paridar, Naser Amirizadeh, Mahyar Habibi Roudkenar, Fatemeh Amiri, Hassan Abolghasemi, Mohammad Ali Jalili,
Volume 6, Issue 3 (5-2014)
Abstract
Background: Hemophilia B is an X-linked hereditary disorder of blood coagulation system which is caused by factor IX (FIX) deficiency. Factor IX is a plasma glycoprotein that participates in the coagulation process leading to the generation of fibrin. Replacement of factor IX with plasma-derived or recombinant factor IX is the conventional treatment for hemophilia B to raise the factor IX level to therapeutic range. Recently, gene therapy has been regarded as a promising approach to treat hemophilia B. This study was aimed to express the factor IX in human amniotic membrane-derived mesenchymal stem cells (hAM-MSCs).
Materials and Methods: Human amniotic membrane-derived mesenchymal stem cells were isolated and characterized from amnion membrane. Factor IX from commercially available plasmid was sub-cloned into pcDNA3.1 vector. Recombinant pcDNA3.1-FIX construct was confirmed by PCR, enzymatic digestion and DNA sequencing. Mesenchymal stem cells were transfected with the recombinant vector. Expression of factor IX was determined by RT-PCR, ELISA and its biological activity assay was performed using aPTT.
Results: Isolated hAM-MSCs expressed specific mesenchymal stem cells markers and were able to differentiate to osteocytes and adipocytes lineages. hAM-MSCs expressed hrFIX at mRNA and protein level. The maximum amount of hrFIX was 120 ng/ml at 72 hrs after hAM-MSCs transfection. This hrFIX was biologically active (11% activity), formed fibrin clot in aPTT test and caused more than two fold decrease in clotting time.
Conclusion: The hAM-MSCs expressing factor IX would be useful for gene therapy of hemophilia B. However further studies are required to prove these finding.
Key words: Hemophilia B, amnion membrane, mesenchymal stem cell, factor IX, gene therapy.
Esfahani H , Bazmamoun H,
Volume 6, Issue 4 (7-2014)
Abstract
Background: Hemophilia A and B are the most frequent congenital coagulation disorders. This study was conducted to determine the prevalence of hepatitis B, C and human immunodeficiency viruses among hemophilic patients in Hamadan, Iran.
Patients and Methods: In this study, patients with hemophilia A and B treated in Hamedan Hemophilia Center, Hamedan, Iran, were screened for hepatitis B, C and human immunodeficiency viruses (HIV) during the year 2012.
Results: The prevalence of hemophilia A and B were 86.5 % and 13.5% respectively, and 57.3% of patients had severe hemophilia. HBS antigen, HCV antibody, HCV PCR and HIV antibody were positive in 1.1%, 49.4%, 16.7% and 1.1% of patients respectively. The prevalence of HCV antibody was higher in those patients receiving cryoprecipitates more frequently.
Conclusion: Hepatitis C infection has a high prevalence in Hamedan Hemophilia Center, Hamedan, Iran, among hemophilic patients. It seems reasonable to use more accurate virus deactivation techniques during blood products preparation or use other safer treatment methods for hemophilia patients.
Keywords: Hepatitis, human immunodeficiency virus, hemophilia.
Beheshtipoor N, Ghanavati Sh, Edraki M, Karimi M, Haghpanah S,
Volume 7, Issue 3 (4-2015)
Abstract
Background: Hemophilia is a chronic bleeding disease and can interfere with daily performance of children. These children require continuous training to prevent bleeding. Since children nurses play an important role in the education of sick children and their self-efficacy and the increase use of educational computer games, the use of educational games for teaching self-efficacy to children with hemophilia can be effective. Therefore, we aimed to explore the impact of computer-based learning games on the self-efficacy of 8-12 year-old children with hemophilia.
Methods: The present study is an experimental interventional study on 40 children with hemophilia aged 8-12 years old during 2014. Data collection tools were a standard self-efficacy questionnaire and patients’ demographic forms. Data were analyzed using SPSS software version 16.
Results: Based on the findings of this study, the mean self-efficacy scores of the samples before, after and one month after intervention were 53.25, 60.95, 60.90 in the case group, and 50.45 and 55.2 in the control group before and one month after the intervention, respectively. The findings revealed that self-efficacy scores after and before the intervention differed significantly.
Conclusion: Educational hemo-action games increased self-efficacy in 8-12 year-old children with hemophilia.
Keywords: Educational games, Computer games, Self-Efficacy, Hemophilia.
Mehrabi Habibabadi H, Amiri F, Moslemi E, Habibi Roudkenar M, Jalili M,
Volume 7, Issue 3 (4-2015)
Abstract
Background: Mesenchymal stem cells (MSCs) are ideal cells for cell and gene therapy. However, the low survival of MSCs after transplantation has limited their applications. We aimed to evaluate the expression of cytoprotective genes including NQO1, TXNRD1, HO-1, GCLC following the over expression of Nrf2 in umbilical cord-derived MSCs (UC-MSCs).
Methods: 3-5 passages of UC-MSCs were cultured. Recombinant vector containing Nrf2 (pcDNA3.1-Nrf2) and empty vector were transfected into MSCs using FuGENE HD. After exposing the cells to UV light stress, RNA extraction and cDNA generation were performed. Using Primer3, software specific primers were designed for Nrf2, NQO1, TXNRD1, HO-1, and GCLC genes and the expression of these genes was evaluated by RT-PCR. The results were semi-quantified and analyzed statistically utilizing Image J2x software and ANOVA test.
Results: The expression of Nrf2 was up-regulated in UC-MSCs after transfection with pcDNA3.1-Nrf2 (P<0.01). Over expression of TXNRD1 and GCLC were also confirmed in these transfected cells (P<0.05 and P<0.01, respectively). However, expression of NQO1 and HO-1 did not alter in the transfected cells with pcDNA3.1-Nrf2 compared with those transfected with empty vector (P>0.05).
Conclusion: Over expression of Nrf2 resulted in the over expression of TXNRD1 and GCLC in MSCs and might be explained by the fact that a known part of Nrf2 cytoprotective mechanisms is controlled by the expression of these genes.
Keywords: Mesenchymal Stem Cells, Over-expression, Nrf2, TXNRD1, GCLCKeywords: Educational games, Computer games, Self-Efficacy, Hemophilia.
M Payandeh, N Amirifard , E Sadeghi, M Sadeghi, M Choubsaz , F Noor Mohammadi Far, ,
Volume 7, Issue 4 (7-2015)
Abstract
Background: Hemophilia is the most frequent severe hereditary hemorrhagic disease due to deficiency of coagulation factors VIII (Hemophilia A) or IX (Hemophilia B) in plasma. We aimed to identify patients with hemophilia in Kermanshah, Iran and assess the incidence of inhibitors in this population and its associated factors.
Methods: This study was conducted on patients with hemophilia A and B admitted in hospitals of Kermanshah city, referred to coagulation laboratory of Kermanshah blood transfusion organization. Variables including age, sex, family history of the patients in terms of history of hemophilia and inhibitor formation, development of inhibitor in patients, age at starting the treatment, blood group, severity of hemophilia, average of factors received per month and liver disease were assessed in patients.
Results: Of 123 patients with hemophilia A, 119 (96.7%) were men. The mean±SD age of patients with hemophilia A was 25.9±15.74 years. Only five men had developed factor VIII inhibitor. Of 25 patients with hemophilia B, 24 (96%) were men with a mean±SD age of 21.7±15.71 years. Factor IX inhibitor was not detected in any patient. There was no association between incidence of inhibitors and age at the onset of the treatment, family history of hemophilia, blood group, severity of hemophilia, average of received factor per month and liver disease. However, a positive association between incidence of inhibitors and family history of inhibitors was found (P<0.05).
Conclusion: Association between family history of inhibitor and incidence of inhibitor formation in hemophilic patients was a new finding. Therefore this outcome and genetic evaluation of these for finding relevant mutations should be considered.
P Eshghi, H Abolghasemi , F Malek , M Naderi , Y Panahi, B Habibpanah, E Fatohlahzadeh, F Gorji,
Volume 7, Issue 4 (7-2015)
Abstract
Background: Considering the increasing number of patients with hemophilia and infrastructure requirements for a comprehensive approach, development of a recombinant factor has become a milestone. The objective of this study was to assess the safety, efficacy and non inferiority of Safacto (Recombinant factor VIII) compared with plasma-derived factor in the treatment of hemophilia A. Methods: 10 patients with severe hemophilia A were enrolled in this study. Each patient was treated by a 40-50 IU/kg infusion of either plasma derived or recombinant factor VIII after initiation of each of 4 consecutive hemarthrosis episodes in a triple-blind prospective crossover permuted block randomizing method. Clinical efficacy scale score and in vivo recovery of factor VIII was assessed in each of the treated bleeding episodes. Any adverse event was also recorded. Results: The mean±SD level of factor VIII in the plasma versus recombinant groups was 111.5±39 and 115±39, respectively without any significant difference. Response scaling method which assessed pain and range of motion revealed equalized scores along with in vivo recovery, hence treatment success rate was comparable in both groups. One non-recurring, mild skin rash reaction occurred simultaneous with the administration of plasma derived factor. Conclusion: Safacto (r-FVIII) is safe and effective and non-inferior to plasma derived factor VIII in the treatment of hemophilia A related bleeding events.
Manijeh Firoozi,
Volume 9, Issue 3 (9-2017)
Abstract
Background: Children with hemophilia are prone to a variety of psychological problems due to some limitations associated with the disease. We aimed to compare the cognitive, emotional, and behavioral problems of children with hemophilia to healthy children.
Methods: This study was performed on 65 children with hemophilia and 65 healthy individuals as the control group who were between the ages of 7 and 12 years in Children’s Hospital. The Child Behavior Checklist (CBCL) was used to identify emotional/behavioral problems and Wisconsin Card Sorting Test (WCST) to evaluate cognitive problems.
Results: The results showed that children with hemophilia obtained lower scores in activity, academic performance, and overall competence variables. Children with hemophilia in comparison to healthy children showed more internalizing and externalizing problems and emotional and behavioral deficits. Also they demonstrated more impairment in executive functions than healthy children.
Conclusion: The bio-psycho-social factors such as factors associated with the disease (e.g. anemia and bleeding), and the treatment (e.g. side effects of the drugs) and environmental and social factors are among underlying causes of some psychological problems in children with hemophilia.
Reza Aminnejad,
Volume 12, Issue 2 (6-2020)
Abstract
Soha Mohammadi Moghaddam, Mitra Khalili, Behnaz Habibpanah,
Volume 13, Issue 4 (12-2021)
Abstract
Repeated bleeding into the joints often occurs in the first decade of life in patients with hemophilia. Joint degeneration is progressive, and although early treatment can slow the process, destruction of the joint is unavoidable. Hemophilic pseudotumors (HPT) are developed due to recurrent bleeding from extra-articular bone or soft tissues.
Dr Atessa Pakfetrat, Dr Najmeh Anbiaee, Dr Amin Rahpeyma, Dr Mehdi Shahabinejad, Dr Zohreh Dalirsani, Dr Zahra Delavarian, Dr Toktam Zamani, Dr Elahe Vazavandi,
Volume 14, Issue 2 (6-2022)
Abstract
Background: Hemophilic pseudotumor is a rare lesion that is progressive and expansile by nature. It is a hematoma or a blood cyst surrounded by a fibrous capsule.
Case report: A 7-years-old boy was referred with a painless swelling in the mandible, bleeding and problem in mastication. Due to a late diagnosis, the patient went untreated for almost a year. After detailed examination and taking medical history as well as paraclinical investigations, including panoramic X-ray, CT (computed tomography), cone-beam CT, and angiography along with laboratory tests, a hemophilic pseudotumor was diagnosed. Treatment plan was set to curettage, coagulation factor injection and regular follow-up. The prognosis was satisfactory and the patient made a full recovery within a year.
Conclusion: A hemophilic pseudotumor is very rare in the jaw and can be diagnosed as a benign or malignant tumor due to its nonspecific radiographic features. Invasive treatment may result in severe bleeding or even death. Therefore, knowledge of the lesion is a prerequisite for careful diagnosis and treatment.
Behnam Azari, Minoo Ahmadinejad,
Volume 16, Issue 2 (6-2024)
Abstract
Von Willebrand Factor (vWF) defects can cause von Willebrand Disease (vWD), which is known to be the most prevalent inherited bleeding disorder worldwide. According to the latest classifications, vWD is categorized into three main types. Types 1 and 3 are quantitative defects, while type 2 vWD is caused by qualitative abnormalities in vWF. Furthermore, ISTH classifies type 2 vWD is into four subtypes known as 2A, 2B, 2N, and 2M. Type 2N vWD is an uncommon type of vWD that is inherited in an autosomal recessive pattern. In this type, the binding capacity of vWF to Factor VIII (FVIII) is reduced, resulting in FVIII's shortened half-life in the patient's plasma. Due to the pathophysiology of Type 2N vWD, affected individuals exhibit signs and symptoms similar to those with mild to moderate hemophilia A. These symptoms include mucocutaneous bleeding or bleeding following trauma or surgery. Furthermore, the primary laboratory findings of affected individuals are comparable to those of hemophilia A patients, with Factor VIII levels ranging from 1 to 40 U/dL. It is crucial to differentiate these disorders for optimal treatment and accurate genetic counseling. Physicians may use a combination of clinical assessment, family history, bleeding scores, and laboratory tests to differentiate between the two disorders. Further genetic testing may be necessary to confirm the diagnosis and assess the risk of inheritance. This review outlines methods for diagnosing type 2N vWD and distinguishing it from hemophilia A, based on published papers and current guidelines.
Fereshteh Karbasian, Maral Nikfarjam, Kiarash Noorizadeh, Ali Abbasi-Kashkooli, Peyman Eshghi, Hamid Reihani,
Volume 16, Issue 2 (6-2024)
Abstract
Background: This study aims to assess the safety level of the different home parts for children with a bleeding tendency disorder (especially hemophilia) and identify the elements that affect this safety.
Materials and methods: We conducted a cross-sectional study on the children referred to the Mofid Children’s Hospital from the beginning of 2018 to the end of 2020. Information was gathered via a checklist. Inclusion criteria were children between 1 to 5 years old with bleeding tendencies, and exclusion criteria were the presence of other disorders. The safety was measured in five areas at home: 1- physical conditions 2- kitchen 3- bathroom 4- toys 5- first aid equipment and essential phone numbers.
Results: Forty-one children participated in this study which 31 (75.61 %) were boys. Eleven (28.95 %) children experienced zero accidents at home and eight (21.05 %) children experienced more than three accidents at home. The Mean and 95% confidence interval scores were 7.97 (7.37-8.57) for the physical condition section, 8.22 (7.73-8.70) for the kitchen section, 8.15 (7.66-8.65) for the bathroom section, 7.93 (7.15-8.71) for the toys section, and 7.30 (6.60-8.01) for the first aid equipment and essential phone numbers section. The physical condition safety score was significantly higher in families whose fathers had a college education than in fathers with secondary and diploma education (P-value = 0.024). The kitchen section safety score was significantly higher in families where the father has a freelance job than the employee or worker (P-value = 0.040).
Conclusion: The mother’s age, father’s educational level, and father’s job are the factors that affect the level of safety significantly. Providing toys that are age-appropriate and safe (without separable parts or holes) could be an important point for parents with children with bleeding disorders.
Babak Abdolkarimi, Javad Rostami , Fatemeh Varehzardi , Shadi Tabibian, Niki Panahi ,
Volume 16, Issue 2 (6-2024)
Abstract
Background: Osteoporosis poses a significant clinical challenge for patients with hemophilia (PWH), primarily due to repeated intra-articular bleeding and joint inflammation. The objective of this study was to assess the impact of a combination of calcium-vitamin D and alendronate tablets on reducing the frequency of hemarthrosis in PWH in Lorestan province.
Methods: This non-randomized controlled trial involved a total of 118 PWH, out of which 55 patients with severe hemophilia A and B. Each patient underwent two assessments including the frequency and duration of bleeding episodes, and improvement in chronic joint pain, before and after receiving a combination of calcium-vitamin D, alendronate, tranexamic acid, and capsaicin ointment. Variables were measured at six-month intervals (at the beginning and end of the study). The statistical software used was SPSS version 21.
Results: The average age of the patients was 33.99 ± 10.67 years. The average number of target joints was 4.18 ± 0.88. A significant correlation was observed between the number of bleeding episodes before and after medication intake (p <0.0001). Similarly, a correlation was found between pre- and post-medication atrophy around the target joint in PWH (p <0.0001). However, no association was detected between joint ankylosis before and after drug administration (p = 0.5). Importantly, there was an improvement in chronic pain post-medication (p <0.0001).
Conclusion: The findings suggest that the combination of calcium-vitamin D and low-dose intermittent alendronate can improve hemophilia joint condition.
Ni Gusti Ayu Galuh Candra Kirana, Suprianto Suprianto, Indra Lesmana, Usi Sukorini, Niken Satuti Nur Handayani,
Volume 16, Issue 4 (12-2024)
Abstract
Introduction: Hemophilia A is a bleeding disorder caused by a deficiency of coagulation factor VIII. Hemophilia A is an X-linked recessive disorder. Depending on the level of blood coagulation factor VIII, hemophilia severity is classified as mild (5-40%), moderate (1-5%), or severe (<1%). The absence of hemophilia A mutation studies in Indonesia makes this topic important to study.
Methods: This study detected and classified F8 gene mutations. A member of the Indonesian Hemophilia Society Association for the Special Region of Yogyakarta provided saliva for DNA testing. Long-read sequencing data were performed using the next-generation sequencing (NGS) technique via the Oxford Nanopore Technologies plc (ONT) PromethION 24 platform. The mutation was confirmed using Sanger sequencing, after amplifying intron 8 of the F8 gene with the PCR technique. The F8 gene intron 8 nucleotide sequence was aligned using the alignment tool on the Benchling website.
Results: The results of this study showed that there was a splice donor site mutation in intron 8 of the F8 gene (c.1271+1G>A) in one patient. This mutation can cause the occurrence of cryptic splice donor sites. Cryptic splice donor site prediction was carried out using the splice donor prediction tool available on the NNSPLICE website. The appearance of cryptic splice donor sites can lead to the formation of out-of-frame proteins.
Conclusions: The F8 gene mutation causing hemophilia A was detected using long-read sequencing and the next-generation sequencing (NGS) technique. The type of mutation identified is a splice donor site mutation, specifically the variant c.1271+1G>A, in sample code HM13.
