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Haemorrhagic disorders combined with soft tissue inflammation and infection may lead to severe bleeding complications before, during or after dental treatment. In selected cases, a combined therapeutic approach involving clinical therapies and systemic and local medication could improve the treatment outcomes and the patient’s quality of life. This clinical case report, presents for the first time a successful combined approach, completed in a 38-year-old male patient with severe type-B haemophilia in which an infected tooth was extracted, an immediate implant was inserted, bone grafting was performed and early implant loading was successfully applied. In addition to the clinical therapy, medication was provided orally, systemically and locally, thus preventing the haemorrhagic complications and improving the patient’s quality of life. [ABSTRACT FROM AUTHOR]

Introduction: Haemophilia is a disease characterised by multiple episodes of spontaneous as well as traumatic bleeding leading to joint pains, joint damage. As a result, there may be disability ultimately leading to a compromised Health Related Quality of Life (HRQoL). This impairment is related to the severity of the clotting factor defect, bleeding frequency and orthopaedic problems. Aim: To find out the correlation of quality of life with functional disability in patients with haemophilia A and B. Materials and Methods: This observational study was conducted from April 2012 to November 2013 on 88 patients with haemophilia A and B, aged between 11 to 50 years. The Physical Component Summary (PCS) and Mental Component Summary (MCS) score was calculated using the short form health survey (SF-36) questionnaire, which is used to assess HRQoL. Gilbert score was used for assessing functional disability. The patients were analysed at initial presentation and then at six months follow-up. All scores were calculated at both times, and comparison was done according to different age groups as well severity of haemophilia. Correlation between SF-36 and Gilbert score was evaluated using various statistical methods. Results: All 88 patients were males with the mean age was 21±9.9 years, with 90.91% being type A haemophilia and 9.09% being type B haemophilia. Clinical presentation of haemophilia patients included bleeding into joints and muscles, gum bleed and epistaxis. Mean scores for PCS and MCS at the initial evaluation were 26.34 and 28.53 and after six months the scores were 29.79 and 29.87, respectively. The overall mean Gilbert score for different age group at initial evaluation and six months were 4.46 and 3.20, respectively. Gilbert score increased with age as well increasing severity of haemophilia. In comparison, PCS and MCS scores decreased with age as well as with increasing severity. Using linear regression and correlation, a negative correlation between functional disability and HRQoL was found. Conclusion: Negative correlation between functional disability and quality of life suggested that when there is increase in functional disability there is a decrease in quality of life. Also, as severity of haemophilia increases the functional disability and quality of life decreases. Therefore, an early intervention in haemophilia patients is important to reduce functional disability. The quality of life can be improved by limiting the functional disability. These findings should aid in improving healthcare delivery to the patients of haemophilia. [ABSTRACT FROM AUTHOR]

Background and Objective: Haemophilia B is a rare genetic disease that is caused by a deficiency of coagulation factor IX (FIX) in the blood and leads to internal and external bleeding. Under the current standard of care, haemophilia is treated either prophylactically or on-demand via intravenous infusions of FIX. These treatment strategies impose a high burden on patients and health care systems as haemophilia B requires lifelong treatment, and FIX is costly. Etranacogene dezaparvovec (ED) is a gene therapy for haemophilia B that has been recently approved by the United States Food and Drug Administration and has received a recommendation for conditional marketing authorization by the European Medicines Agency. We aimed to examine the cost-effectiveness of ED versus extended half-life FIX (EHL-FIX) prophylaxis for moderate-to-severe haemophilia B from a German health care payer perspective., Methods: A microsimulation model was implemented in R. The model used data from the ED phase 3 clinical trial publication and further secondary data sources to simulate and compare patients receiving ED or EHL-FIX prophylaxis over a lifetime horizon, with the potential for ED patients to switch treatment to EHL-FIX prophylaxis when the effectiveness of ED waned. Primary outcomes of this analysis included discounted total costs, discounted quality-adjusted life years (QALYs), incremental cost-effectiveness, and the incremental net monetary benefit. The annual discount rate for costs and effects was 3%. Uncertainty was examined via probabilistic analysis and additional univariate sensitivity analyses., Results: Probabilistic analysis indicated that patients treated with ED instead of EHL-FIX prophylaxis gained 0.50 QALYs and experienced cost savings of EUR 1,179,829 at a price of EUR 1,500,000 per ED treatment. ED was the dominant treatment strategy. At a willingness to pay of EUR 50,000/QALY, the incremental net monetary benefit amounted to EUR 1,204,840., Discussion: Depending on the price, ED can save costs and improve health outcomes of haemophilia patients compared with EHL-FIX prophylaxis, making it a potentially cost-effective alternative. These results are uncertain due to a lack of evidence regarding the long-term effectiveness of ED., (© 2024. The Author(s).)

We report the first case of hemophilia A with factor VIII (FVIII) inhibitor who received hemodialysis via an arteriovenous (AV) fistula. Hemophilia A is a congenital deficiency of blood coagulation FVIII that is characterized by prolonged bleeding. Approximately 30% of patients with hemophilia develop allogeneic antibodies of FVIII. The inhibitors decrease the hemostatic effect of replacement therapy; thus, the prophylaxis strategy should be well designed. Prophylactic treatment with invasive procedures is needed to prevent excessive bleeding in patients with hemophilia undergoing hemodialysis. On the contrary, hemodialysis requires attention to the development of intracircuit coagulation during dialysis. Peritoneal dialysis or hemodialysis with a long-term tunneled central venous catheter has mainly been selected as the dialysis modality for patients with hemophilia and end-stage renal disease requiring renal replacement therapy because hemodialysis with an arteriovenous fistula may result in bleeding from the puncture site after each hemodialysis session. In our patient, hemodialysis was safely performed without any anticoagulant agents, and replacement therapy with FVIII concentrates prevented bleeding after puncture of the AV fistula., (© 2023. The Author(s) under exclusive licence to The Japan Society of Nephrology.)

The cardiopulmonary nematode Angiostrongylus vasorum can cause severe disease in dogs, including coagulopathies manifesting with bleeding. We analysed A. vasorum excretory/secretory protein (ESP)-treated dog plasma and serum by N-terminome analysis using Terminal Amine Isotopic Labelling of Substrates (TAILS) to identify cleaved host substrates. In plasma and serum samples 430 and 475 dog proteins were identified, respectively. A total of eight dog proteins were significantly cleaved at higher levels upon exposure to A. vasorum ESP: of these, three were coagulation factors (factor II, V and IX) and three were complement proteins (complement C3, C4-A and C5). Comparison with human motif sequence orthologues revealed known cleavage sites in coagulation factor IX and II (prothrombin). These and further identified cleavage sites suggest direct or indirect activation or proteolysis of complement and coagulation components through A. vasorum ESP, which contains several proteases. Further studies are needed to validate their substrate specificity. [ABSTRACT FROM AUTHOR]

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Background: Hemophilia B is a rare bleeding disorder in males, characterized by a deficiency in coagulation factor IX (FIX). Replacement of FIX with a recombinant FIX (rFIX) fusion protein, to sustain therapeutic plasma levels, is recommended as both treatment and prophylaxis to prevent bleeding episodes, particularly intracranial hemorrhage (ICH). Case presentation: This case report outlines the management of ICH in a 7-month-old infant with severe hemophilia B, following an accidental trauma-related event, resulting in a thin compound fracture of the left occiput. FIX levels were extremely low (˂1.0%) and large deletions of the coagulation F9 gene (including exons 1–6) were identified. Intensive treatment with a rFIX fusion protein conjugated to the immunoglobulin Fc fragment (rFIXFc) continued for 18 days before hospital discharge. A continuous regimen of weekly rFIXFc infusions was implemented. Thirty days after initiating rFIXFc therapy, neutralizing antibodies or FIX inhibitors (common in patients with large F9 gene deletions) were observed, causing a diffuse skin rash. Such allergic reactions typically indicate progression to potentially serious nephrotic syndrome. A unique immunotolerance regimen of oral oxatomide and intravenous hydrocortisone was started to proactively prevent allergic reactions in this patient during rFIXFc prophylaxis. Even though low titers of the inhibitor (0.6–1.0 Bethesda units) were observed occasionally during subsequent follow-up, there were no signs of further allergies or development of nephrotic syndrome. Conclusion: This is an uncommon case in which rFIXFc was continued despite the appearance of an allergic reaction and the development of FIX inhibitors. Subsequent allergic reactions were prevented with a combination of oral oxatomide and intravenous hydrocortisone given prior to prophylactic rFIXFc. Further studies are recommended to determine the usefulness of this combination with rFIX therapy. [ABSTRACT FROM AUTHOR]

Patients with severe and sometimes moderate hemophilia B are prophylactically treated with factor IX concentrates to prevent bleeding. For some time now, various extended terminal half‐life (EHL) recombinant factor IX concentrates are available allowing less frequent administration during prophylaxis in comparison to standard half‐life recombinant FIX (rFIX). Especially, recombinant FIX‐Fc fusion protein (rFIXFc; Alprolix®) exhibits a rapid distribution phase, potentially due to binding to type IV collagen (Col4) in the extravascular space. Studies suggest that the presence of extravascular rFIXFc is protective against bleeding as without measurable FIX activity in plasma, and no extra bleeding seems to occur. The physiologically based pharmacokinetic (PBPK) model for rFIXFc which we describe in this study, is able to accurately predict the observed concentration‐time profiles of rFIXFc in plasma and is able to quantify the binding of rFIXFc to Col4 in the extravascular space after an intravenous dose of 50 IU/kg rFIXFc in a male population. Our model predicts that the total AUC of rFIXFc bound to Col4 in the extravascular space is approximately 19 times higher compared to the AUC of rFIXFc in plasma. This suggests that rFIXFc present in the extravascular compartment may play an important role in achieving hemostasis after rFIXFc administration. Further studies on extravascular distribution of rFIXFc and the distribution profile of other EHL‐FIX concentrates are needed to evaluate the predictions of our PBPK model and to investigate its clinical relevance. [ABSTRACT FROM AUTHOR]

An important aspect of improving care for people with hemophilia B (HB) is developing optimal treatment strategies. Here we aimed to provide in-silico evidence, comparing the estimated optimal posology of factor IX (FIX) products to support the patient-physician decision-making process. A population pharmacokinetic (popPK) model-based assessment comparing the performance of FIX products (rFIX, rIX-FP, rFIXFc, N9-GP) was developed. PopPK analyses were used to determine a product's optimal posology to target predefined steady-state FIX activity trough levels in a hypothetical population of 10,000 people with severe HB. Model-derived optimal posologies were compared across several parameters including trough levels, proportion of patients per regimen and consumption, considering 64 hypothetical patient scenarios of different FIX trough level targets and ages. Results indicated a marked difference between FIX products estimated to achieve target trough levels, consumption and dosing frequencies. rIX-FP was associated with higher trough levels than rFIX and rFIXFc, at a lower weekly dose and administration frequency, across all age groups. N9-GP use in adolescents and adults was associated with lower consumption compared with rIX-FP. Insights from this study may be utilized by clinicians to inform decision-making, by considering the model-generated estimated optimal posologies alongside multiple clinical factors and patient preferences. [ABSTRACT FROM AUTHOR]

Background: This study aimed to conduct molecular diagnostics among individuals with hemophilia B (HB) and carriers of hemophilia in Mongolia. Methods: Eight patients (six severe, two mild) with HB and their 12 female relatives were enrolled from eight families. Sanger sequence was performed for mutation identification. The questionnaire survey was conducted to evaluate carrier symptoms in female relatives. Results: Two families had a history of HB. A total of five different variants (c.223C > T; c.344A > G; c.464G > C; c.187_188del; and c.1314_1314delA) were identified in six patients with severe HB. Of these, two (c.187_188del and c.1314_1314delA) were novel. No variant in the entire F9 was found in two patients with mild HB. Nonsense c.223C > T (p.Arg75*) mutation was detected in two unrelated patients. Carrier testing identified five mothers as carriers, while one younger sister was a non‐carrier. The carrier status of six female relatives of the two mild patients remained undetermined. By questionnaire survey, only one of the five genetically identified carriers displayed noticeable symptoms of being a carrier. Conclusion: The novel variants c.187_188del and c.1314_1314delA can cause severe hemophilia B. This study did not observe a significant association between symptoms and carrier status in the five carriers. [ABSTRACT FROM AUTHOR]

Disruptions in normal development and the emergence of health conditions often result from the malfunction of vital genes in the human body. Decades of scientific research have focused on techniques to modify or substitute defective genes with healthy alternatives, marking a new era in disease treatment, prevention and cure. Recent strides in science and technology have reshaped our understanding of disorders, medication development and treatment recommendations, with human gene and cell therapy at the forefront of this transformative shift. Its primary objective is the modification of genes or adjustment of cell behaviour for therapeutic purposes. In this review, we focus on the latest advances in gene and cell therapy for treating human genetic diseases, with a particular emphasis on FDA and EMA‐approved therapies and the evolving landscape of genome editing. We examine the current state of innovative gene editing technologies, particularly the CRISPR‐Cas systems. As we explore the progress, ethical considerations and prospects of these innovations, we gain insight into their potential to revolutionize the treatment of genetic diseases, along with a discussion of the challenges associated with their regulatory pathways. This review traces the origins and evolution of these therapies, from conceptual ideas to practical clinical applications, marking a significant milestone in the field of medical science. [ABSTRACT FROM AUTHOR]

Introduction: Quality of Life (QoL) has recently become a focus of research in haemophilia, as children with haemophilia miss out on opportunities to reach their full potential during school and later in life. This leads to emotional and behavioural problems, family issues, and a decrease in Health-related Quality of Life (HRQoL). There is very limited data from the state of Madhya Pradesh, India, to assess the QoL in haemophilia patients. Aim: To study the clinical profile of haemophilic children and assess their QoL. Materials and Methods: The present hospital-based crosssectional study was conducted in the Department of Paediatrics, Gandhi Medical College, Bhopal, Madhya Pradesh, India, from January 2019 to December 2019. A total of 49 children (Institutional incidence), aged from 4-12 years, with factor VIII/ IX deficiency who presented in the Paediatric ward of the study Institution for factor transfusion, were included in the study. The study population was divided into two groups with children aged (group ) and children aged 8-12 years (group II). A detailed clinical history was obtained from the accompanying parent/guardian, and QoL was measured using the Haemophilia QoL (Haemo-QoL) questionnaire. Scores achieved in each dimension, as well as, the total score were combined on a scale ranging from 0 to 100. High values indicate high impairment in QoL. The observations of different scales like Standardised and Transformed Scale Scores (TSS) of Haemo-QoL were analysed using the student's t-test. Results: In the present study, haemophilia A was more common than haemophilia B. All patients who attended the paediatric ward for factor transfusion were males, with a mean age of 8.37±2.56 years. It was also observed that the proportion of patients who were diagnosed early was significantly higher in the 4-7 years age group compared to the 8-12 years age group of patients (p-value <0.05). The present study revealed that the mean overall scores on the Haemo-QoL for the age groups 4-7 years and 8-12 years were 41.92±17.95 and 51.84±16.36, respectively. The highest impairment was in the physical health, school and sports, and family dimensions of QoL. Conclusion: The QoL is poor among children in both age groups. The current study also showed that as age advances, the QoL of haemophilia patients becomes poorer. [ABSTRACT FROM AUTHOR]

The Central Nervous System (CNS) is vulnerable to a range of diseases, including neurodegenerative and oncological conditions, which present significant treatment challenges. The blood–brain barrier (BBB) restricts molecule penetration, complicating the achievement of therapeutic concentrations in the CNS following systemic administration. Gene therapy using recombinant adeno-associated virus (rAAV) vectors emerges as a promising strategy for treating CNS diseases, demonstrated by the registration of six gene therapy products in the past six years and 87 ongoing clinical trials. This review explores the implementation of rAAV vectors in CNS disease treatment, emphasizing AAV biology and vector engineering. Various administration methods—such as intravenous, intrathecal, and intraparenchymal routes—and experimental approaches like intranasal and intramuscular administration are evaluated, discussing their advantages and limitations in different CNS contexts. Additionally, the review underscores the importance of optimizing therapeutic efficacy through the pharmacokinetics (PK) and pharmacodynamics (PD) of rAAV vectors. A comprehensive analysis of clinical trials reveals successes and challenges, including barriers to commercialization. This review provides insights into therapeutic strategies using rAAV vectors in neurological diseases and identifies areas requiring further research, particularly in optimizing rAAV PK/PD. [ABSTRACT FROM AUTHOR]

Food allergy (FA) is estimated to impact up to 10% of the population and is a growing health concern. FA results from a failure in the mucosal immune system to establish or maintain immunological tolerance to innocuous dietary antigens, IgE production, and the release of histamine and other mediators upon exposure to a food allergen. Of the different FAs, peanut allergy has the highest incidence of severe allergic responses, including systemic anaphylaxis. Despite the recent FDA approval of peanut oral immunotherapy and other investigational immunotherapies, a loss of protection following cessation of therapy can occur, suggesting that these therapies do not address the underlying immune response driving FA. Our lab has shown that liver-directed gene therapy with an adeno-associated virus (AAV) vector induces transgene product-specific regulatory T cells (Tregs), eradicates pre-existing pathogenic antibodies, and protects against anaphylaxis in several models, including ovalbumin induced FA. In an epicutaneous peanut allergy mouse model, the hepatic AAV co-expression of four peanut antigens Ara h1, Ara h2, Ara h3, and Ara h6 together or the single expression of Ara h3 prevented the development of a peanut allergy. Since FA patients show a reduction in Treg numbers and/or function, we believe our approach may address this unmet need. [ABSTRACT FROM AUTHOR]

Hemophilia A (HA) is an X-chromosome-linked recessive genetic disorder. Female carriers may have bleeding symptoms, but rarely have moderate or severe disease. We identified a female patient with moderate HA by pedigree tracking and genetic testing in a HA family involving consanguineous marriage. To investigate the clinical and laboratory data, as well as F8 genetic variant affecting members in her family. We constructed a detailed pedigree diagram and performed coagulation analyses, including factor VIII activity (FVIII:C), FVIII inhibitor, and von Willebrand factor antigen (VWF: Ag) on 20 family members. The genomic DNA of 11 members was screened for intron 1 and intron 22 inversions using long-distance real-time polymerase chain reaction (RT-PCR). Their F8 coding genes were sequenced with an automatic next-generation sequencing. Thirteen HA persons with hemophilia (12 males, one female) and 18 female carriers were identified in the family. VWF: Ag level was normal in all 13 persons with hemophilia and 7 carriers tested. The female HA patient had FVIII:C 1.9 IU/dL and was homozygous for F8:c.1918G > T:p.V640F. Genetic testing is conducive to the diagnosis of hemophilia carriers and persons with hemophilia. F8: c.1918G > T:p.V640F is the pathogenic HA variant in this family. In any hemophilia family, we need to pay more attention to female carriers and patients., Competing Interests: Declarations. Ethical approval: The study was approved by the Ethics Committee of Shandong Blood Center and conducted according to the Declaration of Helsinki. Written informed consent was obtained from each enrolled patients. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

With advances in magnetic resonance imaging (MRI) sequences, there has been increased identification of microbleed/microhemorrhage across different population ages, but more commonly in the older age group. These are defined as focal areas of signal loss on gradient echo MRI sequences (T2* and susceptibility-weighted images), which are usually <5 mm in size representing hemosiderin deposition with wide ranges of etiologies. Susceptibilityweighted imaging (SWI) has become a routine MRI sequence for practices across the globe resulting in better identification of these entities. Over the past decade, there has been a better understanding of the clinical significance of microbleeds including their prognostic value in ischemic and hemorrhagic stroke. Cerebral amyloid angiopathy and hypertension are the two most common causes of microbleeds following peripheral and central pattern, respectively. In the younger age group, microbleeds are more common due to familial conditions or a wide range of hypercoagulable states. This review outlines the pathophysiology, prevalence, and clinical implications of cerebral microhemorrhage along with a brief discussion about the technical considerations of SWI. [ABSTRACT FROM AUTHOR]

Background: Opinions in the literature on the impact of cancer on patients with haemophilia are contradictory. There is a lack of data on the clinical presentation and management of cancer in patients with haemophilia (PWH). Methods: Papers were found following a comprehensive search in PubMed, Google Scholar, and Scopus using the terms "cancer" and "haemophilia" without time limits and using the English language as a filter. The references from all the retrieved original articles and reviews were assessed for additional relevant articles. Results: The emergence of malignancies is one of the important causes of morbidity and mortality in PWH. In the past decade, the literature mainly focused on the epidemiology and outcome of blood-borne cancers in the haemophilia patient group, as the incidence of hepatitis B virus (HBV), hepatitis C (HCV), and HIV infection were high among them. However, with the introduction of recombinant clotting factor concentrates (CFCs), physicians now pay attention to non-virus-related malignancies. Bleeding and thrombotic complications are important causes of morbidity and mortality in critically ill patients with cancer; replacement therapy with factor VIII or IX or others should be maintained during antitumour treatment. Conclusion: Overall, managing cancer in patients with haemophilia requires careful evaluation and individualised planning involving a multidisciplinary team of physicians experienced in haematology, oncology, and surgery. [ABSTRACT FROM AUTHOR]

Background: Extended half-life (EHL) factor IX (FIX) concentrates allow for prophylaxis with prolonged dosing intervals and high bleeding protection in persons with hemophilia B. Long-term real-world studies are lacking. Methods: In a retrospective–prospective study, the six-year use of prophylaxis with the EHL recombinant FIX–albumin fusion protein (rIX-FP) was analyzed, comparing outcomes with previous standard half-life (SHL) FIX in patients already on prophylaxis. Results: Prophylaxis with rIX-FP was prescribed in 15 patients (10 severe, 5 moderate; follow-up: 57 ± 17 months). Based on a pharmacokinetic assessment and clinical needs, the first regimen was 47 ± 7 IU/Kg every 9 ± 2 days. All but one patient remained on rIX-FP prophylaxis, adjusting infusion frequency and/or dose; the last prescribed frequency was ≥10 days in 10/13 patients, being reduced in seven and increased in four vs. the first regimen. The weekly FIX dose was unchanged; FIX trough levels were >5% in all patients. The annual infusion number and FIX IU/Kg significantly decreased (~60%) in eight patients previously on SHL FIX prophylaxis, with similar concentrate costs. Very low bleeding rates (most traumatic bleeds and the last quartile of the infusion interval), improved orthopedic and pain scores, unchanged HEAD-US scores and problem joints, and high treatment adherence (>90%) and satisfaction were registered. Conclusions: Personalized, carefully adjusted rIX-FP regimens contribute to the diffusion and optimization of prophylaxis in persons with severe and moderate hemophilia B, with long-term favorable bleeding, joint, and patient-reported outcomes. [ABSTRACT FROM AUTHOR]

• A promising platform for gene delivery clinical trial simulations is provided. • PK/PD analysis is performed for both individual and population modelling approaches. • Model predictions are consistent with the clinical data for haemophilia patients. • A simulation-based modelling approach is proposed to guide initial dose selection. • Simulations show that the increase in FIX activity and ALT level is dose-dependent. Haemophilia B is a bleeding disorder resulting from a deficiency of coagulation factor IX (FIX). Although gene therapy is a potentially curative treatment option, optimising the dosing of therapeutic genes for patients remains a challenge. Detailed simulation of gene delivery systems is required for an improved understanding of the system. Hence, the purpose of this paper is to develop a modelling framework to predict the physiological response of a subject affected by type B haemophilia to a dose of the vector. To address this, an integrated pharmacokinetic/pharmacodynamic (PK/PD) modelling platform was developed based on in vivo clinical data for three patients with severe haemophilia B, whose functional plasma levels of FIX are less than 1% of the normal value. The plasma FIX activity was considered as the pharmacological effect, while the level of serum alanine aminotransferase (ALT) demonstrated the hepatocellular toxicity. Both an individual-based modelling approach and a population modelling approach were used to estimate the physiological parameters of the developed PK/PD models. The models were then validated using data from the clinical study before being used in a simulation-based modelling approach to provide dosing recommendations. The results obtained from the study demonstrate a good prediction of the pharmacokinetics and pharmacodynamics of the vector. Model-based simulations were subsequently performed to guide initial dose selection to provide clinicians with better tools to simplify the decision-making process for designing more effective treatment plans. [ABSTRACT FROM AUTHOR]

Background: 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. [ABSTRACT FROM AUTHOR]

Standard FIX prophylaxis for PWHB require frequent injections, which has led to the development of extended half-life products like rIX-FP (albutrepenonacog alfa) that has shown good efficacy in clinical studies. This ambispective study aims to report a real-world experience with rIX-FP in a Spanish centre with PWHB who switched from SHL-FIX or began prophylaxis with rIX-FP. Five PWHB were included in this study, Four PTP switched to rIX-FP with prophylaxis every 7 days whilst one PUP started with an every-14-days regimen. 3 PTPs extended their dosing intervals to every 14 days or every 21 days. In all PTPs, median annualized spontaneous and joint bleeding rates were maintained at 0.00 and median (range) of ABR was 0.92 (0.00–2.77) after switch to rIX-FP. Mean trough level with previous product was 3.68% (SD = 2.06), while it was 7.08% (SD = 3) with all rIX-FP dosing intervals. After switching to rIX-FP, all PTP reduced their annual infusion rate between 50 and 84% and their annual FIX consumption by 61% (59–67%). This is the first reported real-world experience with albutrepenonacog alfa in a small cohort in Spain and demonstrates good bleeding control together with a reduction of the infusion rate, factor consumption and higher through factor level than previous treatment. [ABSTRACT FROM AUTHOR]

Introduction: The provision of dental care for paediatric patients with inherited bleeding disorders (IBD) can present a challenging scenario for dentists. Although patients with a low bleeding risk can safely receive preventive procedures in the community, many dentists lack confidence when treating this cohort. Consequently, most patients with IBD are seen in hospital dental clinics. There is currently no protocol for shared delivery of primary dental care for paediatric patients with IBD in Australia. Aim: To provide a narrative review of the protocols for oral health management of paediatric patients with inherited bleeding disorders. Materials and methods: An electronic search of four databases relating to the oral health management and outcomes of paediatric patients with IBD was conducted. Results: Thirty-eight papers were included in this review. Several patient and clinician factors in accessing and providing dental care for paediatric patients with IBD were identified. IBD specific considerations for the provision of safe dental care were discussed relating to elective and emergency dental management principles. There was a paucity of paediatric specific protocols for dental management of children with IBD, with only one paediatric specific shared care protocol identified in this review. Conclusions: This review has highlighted the need for further exploration into patient and clinician related barriers and enabling factors in accessing and providing primary dental care for paediatric patients with IBD. The development of a shared model of care between community and hospital dental clinics may improve both clinician and patient experiences in providing and accessing safe dental care. [ABSTRACT FROM AUTHOR]

Introduction: Until extended half-life (EHL) factor IX (FIX) concentrates became available in Japan in 2010, patients with hemophilia B received intravenous FIX replacement therapy with standard half-life (SHL) FIX concentrates. Purpose: To investigate the amount of factor dispensed and the associated medical expenditures for the treatment of hemophilia B in the real-world clinical setting in Japan. Methods: This retrospective study comprised patients with hemophilia B (N=197) who had filled prescriptions for FIX concentrates reported in Japan's Medical Data Vision database from 2015 to 2019. Patients were included if they had 2 or more prescriptions for the same FIX concentrates within the first 6 months of the study period and the interval between prescriptions was at least 2 weeks. Results: Since 2015, there was a decrease in the proportion of patients using SHL FIX concentrates and a corresponding increase in international units of dispensed EHL FIX concentrates. Median annualized dispensed dosages (IU/kg body weight) of EHL FIX concentrates were lower than for SHL concentrates for outpatient use only. Annual total health care expenditures per patient and annual expenditures for prescribed FIX concentrates increased each year during the study period. Following a switch from an SHL to an EHL concentrate, the median amount of prescribed FIX concentrate decreased slightly, although median total health care expenditures and FIX concentrate expenditures increased. Conclusion: In the real-world setting in Japan, medical expenditures and the proportion of patients prescribed EHL FIX concentrates for the treatment of hemophilia B have increased. [ABSTRACT FROM AUTHOR]

Background: Compassionate use is a system that provides patients with expedited access to drugs which has not yet been approved, but currently in clinical trials. The investigational drugs have been authorized for compassionate use in cases involving patients suffered from life-threatening diseases and with no alternative treatments. For instance, patients afflicted with highly heterogeneous rare diseases are eligible for treatment assistance through the compassionate use program. This study aims to investigate the characteristics of compassionate use in the context of rare diseases, evaluate the efficacy and safety of compassionate use for rare diseases, and analyze the marketing approval of investigational drugs. Methods: The case reports/case series of compassionate use were collected by conducting searches on Embase, PubMed, Web of Science, CNKI and SinoMed, spanning from January 1991 to December 2022. Subsequently, two independent reviewers evaluated these reports. Case reports/case series that met the inclusion criteria and exclusion criteria were enrolled. Information extracted from these reports and series included patients' basic information, the investigational drug's name, its indication, adverse events, treatment outcomes, and other relevant data. Results: A total of forty-six studies were included, encompassing 2079 patients with an average age of 38.1 years. Thirty-nine different drugs were involved in 46 studies. Furthermore, neoplasms emerged as the most common therapeutic area for compassionate use in rare disease management (23/46, 50.0%). Regarding the treatment efficacy, four studies reported successful disease resolution, while 35 studies observed symptom improvement among patients. Conversely, four studies documented no significant effects on patients' diseases. Moreover, one study reported worsened results following compassionate use, while the efficacy was not described in 2 studies. Adverse events were reported in 31 studies (67.4%) because of the compassionate use, while no adverse events occurred in 13 studies (28.3%). In other 2 studies, there was no description about whether treatment-emergent adverse events (TEAEs) were happened. 136 patients (6.5%) had Grade 5 adverse events (death), of which 19 deaths (0.9%) were considered to be related to compassionate use. Furthermore, the investigational drugs in 33 studies (33/46, 71.7%) received new drug approval at the end of January 31, 2023.The time lag from the start of the compassionate use to the formal approval of the investigational drug was 790.5 (IQR 359–2199.3) days. We found that in 11 studies, encompassing 9 different drugs, some compassionate use indications had not received regulatory authorities at the end of January 31, 2023. Conclusion: The current status of compassionate use for rare diseases was clarified systematically in this study. Compassionate use of investigational drug is a significant treatment option for rare disease. In general, compassionate use appears to demonstrate favorable efficacy in the context of rare diseases, with a significant proportion of compassionate use drugs subsequently receiving marketing approval. However, the safety of drugs for compassionate use cannot be fully evaluated due to the safety data were not covered in some enrolled studies. Therefore, the establishment of an adverse event reporting system specific to compassionate use is warranted. [ABSTRACT FROM AUTHOR]

Background: Osteoporosis is a bone metabolic disease that usually causes fracture. The improvement of the clinical diagnostic efficiency of osteoporosis is of great significance for the prevention of fracture. The predictive and diagnostic values of bone alkaline phosphatase (B-ALP) and 25-oxhydryl-vitamin D (25-OH-VD) for osteoporotic vertebral compression fractures (OVCFs) were evaluated. Methods: 110 OVCFs patients undergoing percutaneous vertebroplasty were included as subjects and their spinal computed tomography (CT) images were collected. After that, deep convolutional neural network model was employed for intelligent fracture recognition. Next, the patients were randomly enrolled into Ctrl group (65 cases receiving postoperative routine treatment) and VD2 group (65 cases injected with vitamin D2 into muscle after the surgery). In addition, 100 healthy people who participated in physical examination were included in Normal group. The differences in Oswestry dysfunction indexes (ODI), imaging parameters, B-ALP and 25-OH-VD expressions, and quality of life (QOL) scores of patients among the three groups were compared. The values of B-ALP and 25-OH-VD in predicting and diagnosing OVCFs and their correlation with bone density were analyzed. Results: It was demonstrated that computer intelligent medical image technique was more efficient in fracture CT recognition than artificial recognition. In contrast to those among patients in Normal group, B-ALP rose while 25-OH-VD declined among patients in Ctrl and VD2 groups (P < 0.05). Versus those among patients in Ctrl group, ODI, Cobb angle, and B-ALP reduced, while bone density, the height ratio of the injured vertebrae, 25-OH-VD, and QOL score increased among patients in VD2 group after the treatment (P < 0.05). The critical values, accuracy, and areas under the curve (AUC) of the diagnosis of OVCFs by B-ALP and 25-OH-VD amounted to 87.8 μg/L versus 30.3 nmol/L, 86.7% versus 83.3%, and 0.86 versus 0.82, respectively. B-ALP was apparently negatively correlated with bone density (r = − 0.602, P < 0.05), while 25-OH-VD was remarkably positively correlated with bone density (r = 0.576, P < 0.05). Conclusion: To sum up, deep learning-based computer CT image intelligent detection technique could improve the diagnostic efficacy of fracture. B-ALP rose while 25-OH-VD declined among patients with OVCFs and OVCFs could be predicted and diagnosed based on B-ALP and 25-OH-VD. Postoperative intramuscular injection of VD2 could effectively improve the therapeutic effect on patients with OVCFs and QOL. [ABSTRACT FROM AUTHOR]

Objective: This study aims to evaluate the caregiver burden of parents of hemophilia patients and related factors in the southeast region of Turkey, where access to a regular healthcare facility is more complicated than in other areas. Materials and Methods: Twenty-six caregivers of patients with hemophilia were consecutively enrolled in this non-interventional study. Caregiver burden is measured using the “Hemophilia- Associated Caregiver Burden Scale” (HEMOCAB). Results: Hemophilia affects 65.4% of caregivers emotionally, and 92.3% feel the burden caused by financial problems related to hemophilia. The perception of the patients by caregivers was negative in the groups of low educational degree and unstable employment status (P = .037 and P = .017, respectively). The employment status and job changes influence the caregiver burden because of hemophilia (P = .034 and P = .001, respectively). The groups of those who spent greater than 5 hours for transportation to the hemophilia treatment center (HTC) had a higher burden (P = .001). Multiple linear regression analysis analyzed variables affecting HEMOCAB, frequency, and burden total scores. The model created with the burden total score was statistically significant (P = .047). Conclusion: The main factors affecting caregiver burden were educational status, working conditions, and economic difficulties, as well as the length of infusion times and transfer to HTCs. There is a need to develop socioeconomic policies related to these problems. [ABSTRACT FROM AUTHOR]

Recombinant DNA methodology has greatly increased our knowledge of the molecular pathology of the human genome at the same time as providing the means to diagnose inherited disease at the DNA level. Direct detection and analysis of a range of genetic defects are now possible using cloned gene or oligonucleotide probes or by direct sequencing of the disease gene(s). In addition, the use of restriction fragment length polymorphisms (RFLPs) within and around these genes as indirect genetic markers has now potentiated the tracking of disease alleles in affected pedigrees in cases where direct analysis was not feasible. RFLPs associated with linked anonymous segments may also be used not only to diagnose hitherto undetectable disease states, but also for chromosomal localization of the loci responsible. We present here an updated list of reports describing both the direct and the indirect analysis/diagnosis of human inherited disease; it is intended to serve as a guide to current molecular genetic approaches in diagnostic medicine. [ABSTRACT FROM AUTHOR]

Background: Nonacog alfa (recombinant factor IX [FIX]) is approved in China for the control and prevention of bleeding events in patients with hemophilia B. This was the first study to assess prophylaxis and on-demand therapy with recombinant FIX replacement in a real-world setting in China. This study aimed to evaluate the safety and efficacy of nonacog alfa in Chinese patients with hemophilia B., Methods: In this open-label, multicenter study (clinicaltrials.gov identifier NCT02336178), patients received on-demand or prophylactic treatment with intravenous nonacog alfa for approximately 6 months or 50 exposure days, whichever occurred first. The primary safety outcome was medically important events (i.e., development of FIX inhibitors, allergic reactions, and thrombotic events). Key secondary efficacy outcomes included the annualized bleeding rate for on-demand treatment and prophylaxis, response to on-demand treatment, the number of infusions per bleeding event, and the number of breakthrough bleeding events within 48 hours of prophylaxis., Results: Seventy male patients (mean [standard deviation] age 7.8 [7.2] years) were enrolled (on-demand, n = 37; prophylaxis, n = 57 [24 patients were included in both groups]). Thirty-eight (54%) patients had up to 50 FIX exposure days before the study. The only medically important event was a transient low-titer FIX inhibitor (incidence 1.4%, 95% confidence interval, 0-7.7). The mean annualized bleeding rate was 26.3 for on-demand treatment and 6.5 for prophylaxis. A mean (standard deviation) of 1.5 (1.7) nonacog alfa infusions were given per bleeding episode; 78.8% of episodes resolved with 1 infusion. Response was "excellent" or "good" for 88% of the on-demand infusions. Twenty-three bleeding events (n = 11 patients) occurred within 48 hours of 2032 prophylaxis doses (1.13%)., Conclusion: In the real-world setting, nonacog alfa is safe and effective for on-demand treatment and for prophylaxis for patients with hemophilia B in China., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: Hemophilia B is an X-linked congenital bleeding disorder caused by a deficiency of coagulation factor IX (FIX) clotting activity. This study evaluated safety and efficacy of nonacog alfa, a recombinant human blood coagulation FIX replacement product, in males aged 12–65 years with hemophilia B (FIX activity ≤ 2%) with or without inhibitors in India. Methods: In this multicenter, open-label, post-approval phase 4 study, participants were treated for up to 8 weeks, with up to a 4-week screening period and a subsequent post-treatment 28-day safety observation period. Intravenous nonacog alfa 40 IU/kg (range 13–78 IU/kg) was administered at intervals of 3–4 days, in accordance with the approved local product document. Results: A total of 25 participants were enrolled and completed the study. No participants developed FIX inhibitors during the study, experienced treatment-related adverse events (AEs) or serious AEs, or developed a thrombotic event and/or hypersensitivity reaction. No participants experienced bleeding events requiring on-demand treatment with nonacog alfa. Seventeen bleeding episodes (16 spontaneous and 1 traumatic) were reported in 10 participants; all occurred post treatment, with the exception of a minor gum-bleeding event, and were managed without treatment. The mean (SD) annualized total factor consumption (TFC) per patient was 224,582 (75,527) IU; the mean (SD) annualized TFC by weight per patient was 3639 (573) IU/kg. Conclusion: Nonacog alfa was safe and effective for the prevention of hemorrhagic episodes in Indian males with congenital, severe hemophilia B. No participants developed FIX inhibitors, and no new safety signals were reported. [ABSTRACT FROM AUTHOR]

Background: Hemophilia treatment centers (HTC) are multidisciplinary clinics that serve as medical homes for patients with hemophilia and other bleeding or clotting disorders. Traditionally, hemophilia treatment center teams have included hematologists, social workers, nurse coordinators, physical therapists, and in some instances, other healthcare professionals. Objective: This report describes the role of clinical pharmacy services added at 2 HTCs. Method: Retrospective review of services provided by pharmacists integrated into the care team conducted at 2 HTCs. Conclusions: Pharmacists have the knowledge and training to positively contribute to the care of hemophilia treatment center patients. Specifically, with expertise in therapeutic drug monitoring, pharmacokinetics and patient counseling, pharmacists have the ability to manage the cost of care by promoting adherence, minimizing emergency department visits, and assisting providers in formulating optimal treatment plans to improve care for this patient population. [ABSTRACT FROM AUTHOR]

Carriers of the FMR1 premutation (PM) allele are at risk of one or more clinical conditions referred to as FX premutation-associated conditions (FXPAC). Since the FMR1 gene is on the X chromosome, the activation ratio (AR) may impact the risk, age of onset, progression, and severity of these conditions. The aim of this study was to evaluate the reliability of AR measured using different approaches and to investigate potential correlations with clinical outcomes. Molecular and clinical assessments were obtained for 30 PM female participants, and AR was assessed using both Southern blot analysis (AR-Sb) and methylation PCR (AR-mPCR). Higher ARs were associated with lower FMR1 transcript levels for any given repeat length. The higher AR-Sb was significantly associated with performance, verbal, and full-scale IQ scores, confirming previous reports. However, the AR-mPCR was not significantly associated (p > 0.05) with these measures. Similarly, the odds of depression and the number of medical conditions were correlated with higher AR-Sb but not correlated with a higher AR-mPCR. This study suggests that AR-Sb may be a more reliable measure of the AR in female carriers of PM alleles. However, further studies are warranted in a larger sample size to fully evaluate the methylation status in these participants and how it may affect the clinical phenotype. [ABSTRACT FROM AUTHOR]

Hemophilia is an inherited X-linked coagulopathy defined by a deficiency or abnormality in the clotting function of factor VIII (hemophilia A) or factor IX (hemophilia B). The continuous improvement of the treatment has made possible to monitor the patient through their life cycle with the inherent transition of care, initially by caregivers in childhood and later by the patient himself. Alterations associated with age added to chronic diseases are a constant challenge in the comprehensive treatment of the patient. One of the main results related to the use of factors VIII and IX is the development of inhibitors, which are IgG alloantibodies directed to exogenous coagulation factors. The likelihood of developing inhibitors varies from one person with hemophilia to another and depends on the interaction between genetic and environmental factors. This review offers a better understanding of the physiological alterations that allow a comprehensive assessment of the patient with hemophilia. [ABSTRACT FROM AUTHOR]

Objective: Hemophilia is an uncommon disorder that is difficult to diagnose and manage. Effective movement and individual physiotherapy interventions can improve physical activity levels, quality of life, and participation in children with hemophilia. This study aimed to investigate the effects of individually planned exercise on joint health, functional level, pain, participation, and quality of life in children with hemophilia. Materials and Methods: Twenty-nine children with hemophilia (aged 8-18 years) were randomized into either an exercise group with physiotherapists (n = 14) or a counseling home-exercise group (n = 15). Pain, range of motion, and strength were measured using a visual analog scale, goniometer, and digital dynamometer, respectively. Joint health, functional capacity, participation, quality of life, and physical activity were assessed using the Hemophilia Joint Health Status, 6-Minute Walk Test, Canadian Occupation Performance Measure, Pediatrics Quality of Life, and International Physical Activity Questionnaire, respectively. The exercises were planned individually according to the needs of both groups. Additionally, the exercise group performed the exercise with a physiotherapist. Interventions were performed 3 days/week for 8 weeks. Results: The Hemophilia Joint Health Status, 6-Minute Walk Test, Canadian Occupation Performance Measure, International Physical Activity Questionnaire, muscle strength, and range of motion (elbow, knee, and ankle) were significantly improved in both groups (P < .05). Compared with the counseling home-exercise program group, the exercise group had better results in the 6-Minute Walk Test, muscle strength, and range of motion (knee and ankle flexion) (P < .05). No significant difference was found in pain and Pediatrics Quality of Life scores in both groups. Conclusion: Using individually planned exercise in children with hemophilia is an effective physiotherapy approach to improve physical activity, participation, functional level, and joint health. [ABSTRACT FROM AUTHOR]

Publications on the exposure‐effect relationships of factor concentrates for hemophilia treatment are limited, whereas such analyses give insight on treatment efficacy. Our objective was to examine the relationship between the dose, factor VIII (FVIII) levels and bleeding for rFVIII‐SingleChain (lonoctocog alfa, Afstyla). Data from persons with severe hemophilia A on rFVIII‐SingleChain prophylaxis from three clinical trials were combined. The published rFVIII‐SingleChain population pharmacokinetic (PK) model was evaluated and expanded. The probability of bleeding was described with a parametric repeated time‐to‐event (RTTE) model. Data included 2080 bleeds, 2545 chromogenic stage assay, and 3052 one‐stage assay FVIII levels from 241 persons (median age 19 years) followed for median 1090 days. The majority of the bleeds occurred in joints (65%) and the main bleeding reason was trauma (44%). The probability of bleeding decreased during follow‐up and a FVIII level of 8.9 IU/dL (95% confidence interval: 6.9–10.9) decreased the bleeding hazard by 50% compared to a situation without FVIII in plasma. Variability in bleeding hazard between persons with similar FVIII levels was large, and the pre‐study annual bleeding rate explained part of this variability. When a FVIII trough level of 1 or 3 IU/dL is targeted during prophylaxis, simulations predicted two (90% prediction interval [PI]: 0–17) or one (90% PI: 0–11) bleeds per year, respectively. In conclusion, the developed PK‐RTTE model adequately described the relationship between dose, FVIII levels and bleeds for rFVIII‐SingleChain. The obtained estimates were in agreement with those published for the FVIII concentrates BAY 81‐8973 (octocog alfa) and BAY 94‐9027 (damoctocog alfa pegol), indicating similar efficacy to reduce bleeding. [ABSTRACT FROM AUTHOR]

Paediatric check-ups and vaccinations are provided and free of charge in Germany. Despite being hitherto generally well-received and adhered to, it is possible that the lockdown implemented due to the COVID-19 pandemic resulted in delays or even cancellations of critical paediatric visits with healthcare providers. This study attempts to quantify the rate and time to follow-up for check-ups in Germany using the retrospective IQVIATM Disease Analyzer database. Additionally, timely administration of 4 vaccines (Hexavalent, pneumococcal, MMR-V, Rotavirus) was analysed to examine the impact of pandemic restrictions on vaccine uptake. The timeframes which were compared to determine the effects of COVID-19 were June 2018–December 2019 and March 2020–September 2021. The follow-up rates for paediatric check-ups were consistently lower in the COVID-19 phase, but generally ~90%. Follow-up rates for the vaccinations were distinctly higher during COVID-19. The time between events was almost unchanged for check-ups during the pandemic. For check-ups, age at initial event differed by less than a week between the phases. For vaccinations, the age differences were slightly higher, but exceeded one week in only two cases. The results show that the COVID-19 pandemic had little effect on paediatric check-ups and vaccinations in Germany. [ABSTRACT FROM AUTHOR]

Skewed X chromosome inactivation (XCI-S) has been reported to be associated with some X-linked diseases. Several methods have been proposed to estimate the degree of XCI-S (denoted as γ ) for quantitative and qualitative traits based on unrelated females. However, there is no method available for estimating γ based on general pedigrees. Therefore, in this paper, we propose a Bayesian method to obtain the point estimate and the credible interval of γ based on the mixture of general pedigrees and unrelated females (called mixed data for brevity), which is also suitable for only general pedigrees. We consider the truncated normal prior and the uniform prior for γ . Further, we apply the eigenvalue decomposition and Cholesky decomposition to our proposed methods to accelerate the computation speed. We conduct extensive simulation studies to compare the performances of our proposed methods and two existing Bayesian methods which are only applicable to unrelated females. The simulation results show that the incorporation of general pedigrees can improve the efficiency of the point estimation and the precision and the accuracy of the interval estimation of γ . Finally, we apply the proposed methods to the Minnesota Center for Twin and Family Research data for their practical use. [ABSTRACT FROM AUTHOR]

Background: Children with hemophilia have serious, recurrent joint bleeding that causes disabilities. Regular factor VIII concentrate replacements have not yet completely stopped intra-articular subclinical hemorrhages and permanent joint damage. The prevention of joint damage requires the early detection and management of this hemorrhage. Neoangiogenesis is crucial in the development of synovitis after recurrent hemophilic joint bleeding. This study assessed the level of serum Vascular endothelial growth factor A (VEGF-A) as a vascular biomarker in children with hemophilia A to determine its possible role as a diagnostic biomarker for hemophilic arthropathy. Result: A case–control study with 30 male children who had hemophilia A and 30 healthy controls was conducted. Patients had significantly higher serum VEGF-A levels than the control group (specificity was 70.0% and sensitivity was 83.3%). Hemophilia severity and Hemophilia Joint Health Score had a significant positive correlation with VEGF-A. Conclusion: Children with hemophilia A had significantly higher levels of VEGF-A in their serum. Additionally, VEGF-A had a significant positive correlation with Hemophilia Joint Health Score as well as the severity of the disease. In children with hemophilia A, VEGF-A can be used as a marker for early hemophilic arthropathy detection. [ABSTRACT FROM AUTHOR]

Background: Spontaneous spinal epidural hematomas (SSEH), unrelated to trauma, epidural anesthesia, or surgery, are rare in the pediatric population. Here, a 1-year-old male with hemophilia presented with a magnetic resonance (MR)-documented SSEH and was successfully treated with a C5-T10 right hemilaminectomy. Case Description: A 1-year-old male with hemophilia presented with quadriparesis. The holo-spine magnetic resonance imaging with contrast showed a posterior cervicothoracic compressive epidural lesion extending from C3 to L1 consistent with an epidural hematoma. He underwent a C5 to T10 right-sided hemilaminectomy for clot removal, following which his motor deficits fully resolved. A literature review of SSEH attributed to hemophilia revealed that 28 of 38 cases were effectively treated conservatively, while only 10 cases warranted surgical decompression. Conclusion: Select patients with SSEH attributed to hemophilia with severe MR-documented cord/cauda equina compromise and significant accompanying neurological deficits may require emergent surgical decompression. [ABSTRACT FROM AUTHOR]

There is no dietary strategy that has yet been specifically advocated for haemophilia. Therefore, we sought to assess the effect of the Dietary Approaches to Stop Hypertension (DASH) diet in adolescents with haemophilia. In this parallel trial, forty male adolescents with haemophilia were dichotomised into the DASH group or control group for 10 weeks. The serum high sensitivity C-reactive protein, IL-6, complete blood count (CBC), serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase, partial thromboplastin time (PTT), waist circumference (WC), percentage of body fat, fat-free mass and liver steatosis were measured at the beginning and end of the study. Serum vitamin C was measured as a biomarker of compliance with the DASH diet. The DASH diet was designed to include high amounts of whole grains, fruits, vegetables and low-fat dairy products, as well as low amounts of saturated fats, cholesterol, refined grains, sweets and red meat. Serum vitamin C in the DASH group was significantly increased compared with the control (P = 0·001). There was a significant reduction in WC (P = 0·005), fat mass (P = 0·006), hepatic fibrosis (P = 0·02) and PTT (P = 0·008) in the DASH group, compared with the control. However, there were no significant differences regarding other selected outcomes between groups. Patients in the DASH group had significantly greater increase in the levels of erythrocyte, Hb and haematocrit, as compared with the control. Adherence to the DASH diet in children with haemophilia yielded significant beneficial effects on body composition, CBC, inflammation and liver function. [ABSTRACT FROM AUTHOR]

Introduction: Mandibular pseudotumors, also known as blood cysts, are rare complications which occur more frequently in patients with an associated bleeding disorder such as hemophilia. Case Report: We present a case of a 2-year and 6-month-old patient with a hemophilic pseudotumor associated with Von Willebrand's disease, who consulted the emergency room due to spontaneous increase in volume of the left maxillary region, with no previous relevant medical history. Conclusions: Different imaging studies were carried out to characterize the lesion, providing the necessary information for the correct approach. Due to the low prevalence of this complication, we believe it is of vital importance to understand the adequate management in this patient population. [ABSTRACT FROM AUTHOR]

Background: Hemophilia A (HA) and B (HB) are X-linked recessive disorders that mainly affect males born from a mother carrier. Females are rarely affected but a number of mechanisms have been suggested in symptomatic females, such as skewed X-chromosome inactivation (XCI), chromosomal rearrangements, and hermaphrodites. Different methodologies are required to elucidate the underlying causes of such diseases in female patients. Methods: Three families with female hemophilia patients, including two HA and one HB, were enrolled for genetic analyses. Cytogenetics, molecular examinations on F8 and F9 genes, XCI assay, and linkage analysis were performed. Results: All three female patients are demonstrated to be heterozygous for an F8, or F9 mutation: one patient is inherited from her unaffected mother and the other two are sporadic cases. All three patients exhibit skewed XCI. The inherited patient is found to be unmethylated in the maternal X chromosome, which increases the potential for the expression of the mutant allele. The two sporadic cases are hypomethylated or unmethylated in the paternal X chromosome, suggesting that paternal gonadal mosaicism may exist in these families. Conclusions: In addition to screening for coagulation function, different genetic analyses are mandatory to explore the nature of mechanisms responsible for the X-linked recessive disorders in female patients as shown in this study. Our results confirm that skewed XCI is responsible for hemophilia in heterozygous female patients. Likewise, our results implicate that parental gonadal mosaicism, followed by skewed XCI, contributes to hemophilia in "sporadic" female patients. [ABSTRACT FROM AUTHOR]

Objectives: Changes in coagulation indexes, thromboelastogram(TEG) and autoantibodies in patients with recurrent pregnancy loss (RPL) with different number of abortions were analyzed. Methods: Medical records of 48 patients with recurrent abortion, treated in Quzhou people’s Hospital from November 2019 to October 2020, were collected as the observation group. Based on the number of abortions, patients were divided into Group-A (Two abortions, n=21), Group-B (Three abortions, n=16) and group C (Abortion ≥ four times, n=11). Records of 50 healthy pregnant women in our hospital in the same period were selected as the control group. Coagulation indexes [prothrombin time (PT), activated partial prothrombin time (APTT), fibrinogen (FIB), D-Dimer (DD)], thromboelastogram (TEG) parameters [reaction time (R), coagulation time(K), maximum thrombus amplitude (MA), coagulation angle (α)], changes in the levels of autoantibodies [anticardiolipin antibody (ACA), anti-endometrial antibody (EmAb), anti-thyroid antibody(ATA)] were compared between the groups. Results: There were significant differences in the levels of ATPP, Pt, FIB and DD among the groups. Higher number of abortions correlated with lower the levels of ATPP and Pt, and higher levels of FIB and DD (P<0.05). Compared to the control group, R and K in Group-A,B and C decreased, while α and MA increased (P<0.05). There were significant differences in α and MA indexes. The positive rates of ACA, EmAb and ATA in Group-A were higher than those in the control group, but the difference was not statistically significant (P>0.05), while the above indexes in groups B and C were significantly higher than those in the control group(P<0.05). The positive rates of ACA and ATA in group C were significantly higher than those in Group- A(P<0.05), but there was no significant difference in the positive rate of EmAb (P>0.05). Conclusion: RPL was related to the decrease of APTT, PT, and the increase of FIB and DD levels. TEG indicated that the increase of α and MA values indicated that the risk of multiple abortion was increased. The positive rates of ACA, EmAb and ATA were closely related to multiple abortions, especially the positive rates of ACA and ATA. [ABSTRACT FROM AUTHOR]