proteins

2026-09-03 | Prophylaxis in patients with moderate and mild haemophilia: experience from a single centre

Introduction: Prophylaxis in hemophilia as a gold standard of treatment was classically restricted to patients with severe forms.Objective: To evaluate the implementation of prophylaxis in patients with moderate and mild hemophilia, addressing its impact on the reduction of bleeding and quality of life.Material and methods: Nine patients were included, analyzing retrospective data 12 months before and after starting prophylaxis collected from their electronic medical records.Results: It's observed a significant reduction in annualized bleeding rate by 96.78% for hemophilia A and 91.67% for hemophilia B. Concentrates of factors VIII and IX were used with different infusion regimens.Prophylaxis improved hospital independence and decreased joint bleeding, although with a burden associated with treatment.Conclusions: The need for early follow-up and adoption of prophylaxis in non-severe patients to prevent arthropathies and improve quality of life is highlighted, in line with international recommendations.

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2026-06-23 | Nonacog Beta Pegol (N9-Gp) Prophylaxis in Pediatric Patients with Severe Hemophilia B: A Single Center Real World Experience.

Hemophilia B (Christmas disease) is a rare genetic bleeding disorder. Frequent FIX prophylaxis is challenging in pediatric patients because of difficult venous access and pain during factor administration. Nonacog beta pegol (N9-GP) is an extended half-life (EHL) recombinant FIX. The study assessed the efficacy of Nonacog beta pegol (N9-GP) in reducing bleeding episodes and its safety as prophylaxis in pediatric patients. The primary end-point was reduction in Annual bleeding rates (ABR) and Annual Joint bleeding rates (AJBR). The secondary objectives were to assess the days of school absenteeism, number of emergency visits, measurement of Hemophilia Joint Health Score (HJHS) 2.1 score, pediatric Hemophilia Activities List (pedHAL) score, development of inhibitor against FIX during treatment, and safety & adverse effects (AEs) profile. Ten pediatric patients managed with on-demand SHL FIX were included in the study. Their median age at study entry was 3 years (range, 1-13 years). The median duration of follow-up was 12 months (range, 6-60 months). They were subsequently started on N9-GP prophylaxis, and the mean duration of follow-up was 24 months (range, 11-30 months). There was a significant reduction in ABR (p-value, 0.002), AJBR (p-value, 0.022), and improvement in HJHS, pedHAL score, and reduction in school absenteeism in these children. Four patients experienced bleeding, which required treatment. Two patients developed an inhibitor to N9-GP. Mild adverse effects were noted in 20% of the patients. N9-GP prophylaxis compared to PD/r FIX replacement is a safe and effective strategy in prevention of bleeds, improving QOL and reducing joint related disability in pediatric patients with Hemophilia B.

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2026-02-04 | A specific FX activator for bleeding treatment in hemophilia with inhibitors: multicenter, open-label, phase I/II trials

Bemiltenase alfa, a factor X (FX) activator derived from Daboia russelii siamensis venom, was developed as a hemostatic agent for hemophilia A and B with inhibitors (HAwI and HBwI). We conducted two consecutives multicenter, open-label clinical trials. The phase Ib/IIa study assessed the safety, hemostatic efficacy, and pharmacokinetics/pharmacodynamics characteristics of bemiltenase alfa at a dose of 0.1U/kg. The phase IIb study further evaluated the safety and efficacy at a dose of 0.1U/kg. Primary efficacy endpoints encompassed the effective hemostasis rate, safety assessment and anti-drug antibodies (ADAs) development. There were six participants enrolled in phase Ib study, 20 in phase IIa and 25 in phase IIb study. Patients received bemiltenase alfa for bleeding episodes in phase IIa and IIb studies. In phase IIa, the effective hemostasis rates were 94.1% (95% CI: 88.7-97.4). Phase IIb showed an 81.9% rate (95% CI: 71.0-92.9). Most adverse events were mild with grade one in severity, with no serious events. ADA was detected in five patients, but no impact on efficacy and safety was found. Pharmacokinetics findings showed repeated doses of bemiltenase alfa resulted in progressive drug concentration, as indicated by the accumulation ratio index. Pharmacodynamics results indicated a reduction in activated partial thromboplastin time and an increase in thrombin generation peak. Additionally, a mild decline in FX activity was observed post-administration. The study demonstrates FX activation as a novel hemostatic strategy, with snake venom-derived bemiltenase alfa showing promising safety and efficacy for treating bleeding episodes in HAwI and HBwI patients. (clinicaltrials.gov: NCT05027230, NCT06289166).

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2026-02-01 | Real-World Effectiveness and Usage of Recombinant Factor IX Fc: Final Data from the B-MORE Study

Introduction Extended half-life (EHL) recombinant factor IX Fc fusion protein (rFIXFc) has an established efficacy and safety profile in people with hemophilia B across all ages. Here, we report final data from B-MORE (NCT03901755), a real-world, 24-month prospective study evaluating rFIXFc effectiveness and usage across Europe and the Middle East. Method Eligible patients, including previously untreated patients, were prescribed rFIXFc prophylaxis (PPX) or on-demand prior to/at enrolment. Twelve-month retrospective data on previous FIX (as available), baseline characteristics, and follow-up on rFIXFc (retrospective/prospective periods) are reported. Annualized endpoints only include patients with≥6 months treatment. Results B-MORE enrolled 151 patients from 29 centers (median [range] age: 20.5 [1–81] years; three patients were female). Twelve patients were previously untreated; 119 had severe hemophilia (26 moderate, 6 mild). For the primary endpoints, 137 patients prospectively treated with rFIXFc PPX were analyzed (mean [range] treatment duration: 22.4 [7.3–30.0] months). Median (interquartile range [IQR]) annualized bleeding rate (ABR) was 0.45 (0.0–1.2), annualized injection frequency (IF) was 52.5 (52.2–52.6), and annualized factor consumption (FC) was 2,442.7 (2,021.9–2,969.7) IU/kg/year. An intrapatient comparison was conducted in 92 patients switching from prior standard half-life (SHL) FIX PPX to rFIXFc PPX (mean [range] duration: 11.5 [6.4–12.0] vs 40.6 [9.8–83.3] months, since rFIXFc PPX initiation). In these patients, median (IQR) change in ABR was 0.0 (-1.0–0.4), change in IF was -52.7 (-56.6– -38.4), and change in FC was -1,379.9 (-2,594.4– -264.3; n=91) IU/kg/year. Overall, most physicians (88.5%; 69/78) and patients (90.0%; 90/100) were satisfied/highly satisfied with rFIXFc PPX, at last assessment. No inhibitor development or serious adverse events related to rFIXFc were reported. Conclusion Real-world B-MORE data confirm the effectiveness of rFIXFc and demonstrate that rFIXFc PPX can reduce IF and FC while improving/maintaining bleed protection, compared with SHL PPX. B-MORE is sponsored by Sobi. Publication History Article published online: 17 February 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany

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2025-10-25 | Complications of the Patient with Hemophilia Associated with Transfusion of Blood Components or Derivatives: 35 Cases

Hemophilia is a congenital bleeding disorder characterized by deficient or absent clotting factors, most commonly Factor VIII (Hemophilia A) or Factor IX (Hemophilia B). Regular transfusions of blood products, such as clotting factor concentrates and plasma derivatives, are essential in managing bleeding episodes in hemophilic patients. However, transfusion therapy is not without risks. This study aims to explore the complications associated with blood component transfusion in 35 hemophilic patients, analyzing a range of adverse events that arose following transfusion therapy. The study retrospectively reviewed the medical records of 35 hemophilic patients who received blood component transfusions over a 2-years period. Data were collected on the type of transfused products, the number of transfusions, and the complications encountered. These complications included allergic reactions, the development of inhibitors (antibodies against transfused clotting factors), viral infections (such as hepatitis and HIV), iron overload, and thrombotic events. A total of 35 hemophilic patients (27 male, 8 female) participated in this study. The mean age was 34.2 years, with a range spanning from 8 to 68 years. Hemophilia A (n = 22, 62.9%) was more common than Hemophilia B (n = 13, 37.1%). The severity of hemophilia was categorized as severe (n = 15, 42.9%), moderate (n = 12, 34.3%), and mild (n = 8, 22.8%). The mean number of transfusions per patient was 10.3, with clotting factor concentrates being the most frequently used transfusion product (n = 29, 82.9%). The study revealed a 34% complication rate (n = 12). The most common complications were allergic reactions (14.3%), inhibitor development (20%), and iron overload (11.4%). Thrombotic events were less frequent (5.7%), while one case of hepatitis B (2.9%) was noted, which was attributed to older plasma-derived factor products. Statistical analysis showed a significant correlation between severe hemophilia and inhibitor development (71% of severe cases developed inhibitors, p < 0.05). No significant association was observed between transfusion product type and the occurrence of complications. The study highlights the need for careful monitoring and management of hemophilic patients receiving transfusions. Strategies to minimize risks, such as the use of recombinant clotting factors, individualized transfusion protocols, and regular screening for inhibitors, are critical in improving patient outcomes and reducing complications.

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small molecules

2026-01-01 | Evidence-based dental management strategies for individuals with congenital hemophilia: a systematic review

Abstract Background People with hemophilia commonly present with a range of bleeding symptoms, from minor oral cavity bleeds to life-threatening events such as intracranial hemorrhage. People with hemophilia often exhibit poor oral health, attributed to disease-specific barriers and a fear of dental procedures, which may exacerbate their oral disease burden. This systematic review aimed to evaluate the various dental procedures performed in patients with hemophilia and the corresponding clotting factor concentrate replacement regimens used for individuals with mild, moderate, and severe forms of the disease. Methods An electronic database search was carried out using MEDLINE by PubMed, Scopus, Google Scholar, Web of Science, ProQuest, CINAHL, EBSCO Dental collection and EMBASE databases from inception to March 2025 for studies published in English language. The search strategy terms included were “hemophilia A”, “hemophilia A”, “hemophilia B”, “hemophilia B”, “dental care”, “oral surgery”, “complications”, “bleeding”. Case control studies, randomized controlled trials, observational studies and case reports addressing the dental treatments for people with hemophilia A/hemophilia B were included. Cases of acquired hemophilia and cases of hemophilia who are inhibitor positive were excluded. Results A total of 23 studies were included for the final review. Majority of the studies have ensured to achieve 30% to 50% factor correction for dental procedures. Routine dental care procedures like restoration and dental scaling with the necessary technical specifications can be safely performed. Dental extractions can be safely performed using local infiltration anesthesia; however, administering nerve blocks typically necessitates prior administration of clotting factors due to the elevated bleeding risk. Adjuvant systemic anti-fibrinolytics like Epsilon-aminocaproic acid (EACA) and tranexamic acid greatly reduces the need for additional factor infusion. Conclusions The use of prophylactic clotting factors during dental interventions in hemophilia patients showed notable inconsistencies across studies. This inconsistency underscores the importance of conducting larger, prospective clinical studies to better understand the rationale behind clotting factor use and its effects on dental treatment outcomes in patients with varying degrees of hemophilia severity.

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2024-11-29 | Non-factor Therapies for Hemophilia: Achievements and Perspectives

Non-factor replacement therapies (NFTs) have been developed to address the limitations of conventional replacement therapies, aiming to improve hemostasis and provide enhanced protection against bleeding episodes and long-term joint damage for patients both with and without inhibitors. Factor VIII (FVIII)-mimetic agents, such as emicizumab, have transformed the management of hemophilia A with inhibitors, offering a lower treatment burden and an effective alternative for those without inhibitors as well. Rebalancing agents, including anti-tissular factor pathway inhibitor agents (concizumab and marstacimab) and serpin inhibitors like fitusiran, have shown promising efficacy for patients with hemophilia B with inhibitors and other hemophilia subtypes. Administered subcutaneously, NFTs generate stable thrombin levels and feature a long half-life, which can shift severe hemophilia toward a milder phenotype. These therapies are effective regardless of inhibitor status and hold potential for application in other bleeding disorders. Evaluating the potential thrombotic risk after implementing mitigation measures, along with the development of anti-drug antibodies (ADAs), remain critical areas for further analysis. NFTs pose additional challenges due to their complex mechanism of action and the absence of a standardized laboratory assessment method. Unresolved issues include optimal management strategies for major surgeries and tailored approaches for safe use in older populations. This review highlights the progress and future potential of NFTs in treating persons with hemophilia.

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2024-09-09 | Drug-induced liver injury related to gene therapy: A new challenge to be managed.

Gene therapy is being successfully developed for the treatment of several genetic disorders. Various methods of gene transfer have been developed to enable the production of the deficient enzyme or protein. One of the most important is adeno-associated virus vectors, which have been shown to be viable for use in in vivo gene therapy. Several gene therapies have already been approved. They are also promising for acquired diseases. Important examples include gene therapy for haemophilia A and B, X-linked myotubular myopathy, spinal muscular atrophy and several liver diseases such as Criggler-Najjar disease, alpha-1 antitrypsin deficiency and Fabry disease. However, the introduction of a foreign compound into hepatocytes leads to hepatic reactions with heterogeneous phenotypic expression and a wide spectrum of severity, ranging from mild transaminase elevation to acute liver failure. Several mechanisms appear to be involved in liver injury, including an immune response, but also direct toxicity depending on the method of gene transfer. As a result, the incidence, expression and severity of liver injury vary from indication to indication and from patient to patient. Patients treated for haemophilia A are more prone to transaminase elevation than those treated for haemophilia B. Corticosteroids are successfully used to correct liver reactions but also to prevent degradation of the transferred gene and loss of therapeutic activity. The aim of this review is to describe the risk of liver injury according to the indication for gene therapy and the short- and long-term management currently proposed to prevent or correct liver reactions in clinical practice.

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2021-09-24 | The role of total ankle replacement in patients with haemophilia and end-stage ankle arthropathy: A review.

Haemophilia is the most common X-linked bleeding disorder, affecting over 1 million individuals throughout the world. Patients are subclassified into mild, moderate and severe disease based on per cent factor activity level. Nearly, all patients with haemophilia develop haemophilic arthropathy (HA) by age 30 and HA is known to have a negative impact on physical health subscores in Haem-A-QOL, a validated quality of life scoring system for patients with haemophilia. Unfortunately, many patients progress to end-stage HA of the ankle, which is characterized by pain, contractures, decreased range of motion and muscle atrophy. Ankle arthrodesis (AAD) has been the standard of care in the definitive surgical management of end-stage HA of the ankle. While AAD is a safe surgical procedure known to improve HA-related pain, it decreases functional mobility and has been associated with secondary hindfoot arthritis as well as subtalar degeneration. In recent years, total ankle replacement (TAR) has emerged as an alternative surgical procedure that strives to improve functional mobility, pain and quality of life in end-stage HA of the ankle. However, the safety, durability, and efficacy of this procedure in these patients are unknown. In this review, we analyse the clinical studies investigating TAR in patients with end-stage HA of the ankle. We also discuss important considerations in the perioperative management of patients with haemophilia and compare the risks and benefits of AAD and TAR for patients with end-stage HA of the ankle.

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2021-01-18 | [Diagnosis and management of hemophilia].

Hemophilia A and B are hereditary coagulation disorders caused by functional and quantitative abnormalities of coagulation factor VIII (FVIII) in hemophilia A and coagulation factor IX (FIX) in hemophilia B. A definitive diagnosis is made through the measurement of FVIII or FIX activity and ruling out other pathological conditions or diseases with decreased FVIII or FIX activity. Severity is classified as severe, moderate, and mild according to factor activity level. Moreover, as frequency of hemorrhage and severity are usually correlated, severe patients have a high risk of intracranial hemorrhage during infancy as well as joint damage due to recurrent hemarthrosis. However, there are some non-severe patients who have symptoms like bleeding and joint damage. Therefore, it is necessary to determine the treatment strategy not only based on severity but also on bleeding symptoms. The treatment for hemophilia is mainly replacement therapy using clotting factor concentrates (standard or extended half-life), such as prophylaxis or on-demand therapy for bleeding. However, there are also clinical problems, such as venous access and development of inhibitors. Recently, a non-factor agent has emerged as a new treatment option. Thus, the management of hemophilia is on a turning point.

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gene therapies

2026-09-02 | NHLBI TOPMed: My Life Our Future (MLOF) Research Repository of Patients with Hemophilia A (Factor VIII Deficiency) or Hemophilia B (Factor IX Deficiency)

Hemophilia A and B are X-linked bleeding disorders resulting from a deficiency in coagulation factor VIII (FVIII) or factor IX (FIX), respectively. Hemophilia affects approximately 1/5000 male births worldwide, and results in premature death and disability due to bleeding if coagulation factor replacement therapy is not used effectively. Hemophilia is clinically categorized by coagulation factor activity levels and ranges in severity from mild (6% to 30%) to moderate (1-5%) to severe (<1%). Many female "carriers" of hemophilia also have decreased factor activity and morbidity from bleeding. Hemophilia A and B are almost always caused by identifiable mutations in the F8 and F9 genes, respectively, and these mutations are found throughout the structural genes. Although the hemophilias are monogenic disorders, there are wide variations in disease severity and therapeutic outcomes which are not readily explained by the disease causing mutations alone. The My Life Our Future (MLOF) project ([www.mylifeourfuture.org](http://www.mylifeourfuture.org)) is a national resource developed by a partnership of BloodworksNW (BWNW, formerly the Puget Sound Blood Center), the American Thrombosis and Hemostasis Network (ATHN), the National Hemophilia Foundation (NHF) and Bioverativ, to provide free F8 and F9 gene variant analysis to patients with hemophilia A or B, and to establish a research repository of DNA sequence, DNA, RNA, buffy coat, serum and plasma. The sequence analysis and serum samples are linked to a phenotypic database hosted by ATHN, with samples submitted and clinical data entered at ~100 hemophilia treatment centers (HTCs) nationwide. (See ATHN Research Report Brief in the resource center at [www.athn.org](http://www.athn.org)). MLOF has become the largest hemophilia genetic project worldwide. The roles of the MLOF partners are: BWNW, to serve as the central laboratory for the project and house the research repository; ATHN, to support and provide the administrative link with HTCs, to facilitate the collection of accurate phenotypic data, to conduct research review and approval for use of the repository and with BWNW to provide samples and data for research projects; NHF, to provide consumer education and facilitate consumer input into the project; and Bioverativ, to provide financial support and scientific input. The project is governed by a Steering Committee consisting of one representative from each organization. Subject samples chosen from the MLOF parent study for TOPMed and WGS were drawn from those who gave (or parents gave) informed consent for the Research Repository and included patients of all severities and type, but with an emphasis on those with severe hemophilia and others at increased risk of neutralizing antibody (inhibitor) formation and who had samples in the Research Repository (plasma, serum, RNA) for potential additional -omic studies. Also included were samples from subjects where a likely causative variant for hemophilia was not found in the F8 or F9 coding region, intron-exon boundaries or immediate upstream and downstream regions. Since hemophilia is an X-linked disorder, the majority of subjects are male. Racial distribution is similar to the overall population distribution.

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2026-08-17 | CLINICAL PROFILE, DISEASE SEVERITY, AND MANAGEMENT OF HEMOPHILIA PATIENTS: A CROSS-SECTIONAL STUDY FROM NORTH BENGAL

Background: Hemophilia is the most common inherited severe bleeding disorder, with limited data available from the resource-constrained regions of North Bengal. The establishment of the Hemoglobinopathies and Hemophilia Control Unit (HHCU) has facilitated structured diagnosis and management of hemophilia across India, including the sub-Himalayan region of North Bengal. The objective is to evaluate the clinicodemographic profile, disease severity, clinical manifestations, and management practices of hemophilia patients attending a tertiary care center in North Bengal. Materials and Methods: A hospital-based cross-sectional study was conducted at a tertiary care hospital from January 2022 to June 2026. All diagnosed hemophilia patients attending the HHCU during the study period were included. Clinical characteristics, family history, coagulation parameters (PT/INR and aPTT), factor assay findings, and treatment details were collected and analyzed. Results: A total of 76 patients with hemophilia were enrolled in the study. Among them, 52 (68.4%) patients belonged to the 11–25 years age group, while 24 (31.6%) were between 1 and 10 years of age. Of the 76 patients, 70 (92.1%) were diagnosed with Hemophilia A and 6 (7.9%) with Hemophilia B. Based on factor activity levels, 40 (52.6%) patients had severe disease, 31 (40.8%) had moderate disease, and 5 (6.6%) had mild disease. The most common clinical presentation was hemarthrosis, observed in 39 (51.3%) patients, followed by gum bleeding in 18 (23.7%), epistaxis in 10 (13.2%), and joint deformities in 9 (11.8%) patients. Prolonged activated partial thromboplastin time (aPTT) was observed in most patients, whereas prothrombin time/international normalized ratio (PT/INR) remained within the normal range. Recombinant factor concentrates were administered on demand to 58 patients, while prophylactic therapy was initiated in 5 children before the development of established joint deformities. All patients were provided with government-issued unique identification cards. Conclusion: Hemophilia A with severe factor deficiency was the predominant disease pattern in this cohort. The HHCU has substantially improved access to diagnosis, factor replacement therapy, prophylactic care, rehabilitation services, and patient awareness in North Bengal. Despite these advances, significant gaps remain in specialized diagnostic facilities and comprehensive long-term care, particularly for patients residing in rural areas.

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2026-07-15 | Clinico-Demographic Profile and Management Scenario of Hemophilia Patients in a Tertiary Care Centre of North Bengal – A Cross-Sectional Study

Background: Haemophilia is the most common inherited severe bleeding disorder, with limited data available from resource-constrained regions of North Bengal. The establishment of the Hemoglobinopathies and Hemophilia Control Unit (HHCU) has enabled structured diagnosis and management in this sub-Himalayan region. Objectives: To evaluate the clinico-demographic profile, severity distribution, clinical manifestations, and management practices of haemophilia patients attending a tertiary care centre in North Bengal. Methods: A hospital-based cross-sectional study was conducted at Jalpaiguri Government Medical College and Hospital from 2022 to 2025. All diagnosed haemophilia patients attending the HHCU during the study period were included. Clinical details, family history, PT/INR, aPTT, factor assays, and treatment data were analysed. Results: A total of 66 patients were enrolled, of whom 61 (92.5%) had haemophilia A and 5 (7.5%) had haemophilia B. The majority belonged to the 11–25-year age group (68.2%). Severe disease was observed in 34 (55.7%) patients, moderate in 23 (37.7%), and mild in 4 (6.6%). Hemarthrosis was the most common presentation (50%), followed by gum bleeding (24.2%), epistaxis (13.6%), and joint deformities (12.2%). The knee joint was most frequently affected (45%). Prolonged aPTT was noted in most cases, whereas PT/INR remained normal. Recombinant factor concentrates were administered on-demand in 58 patients, and prophylactic therapy was initiated in five children without established joint deformities. All patients received government-issued unique identification cards. Conclusions: Haemophilia A with severe factor deficiency constituted the predominant disease pattern in this cohort. The HHCU has significantly improved diagnostic access, factor replacement therapy, prophylactic care, rehabilitation support, and patient awareness in North Bengal. Despite recent advances, substantial unmet needs remain in specialized diagnostic facilities and long-term comprehensive care for the rural population of this region

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2026-04-14 | Haemophilia Joint Health Score Ranges Across the Lifespan: Variation by Haemophilia Type and Severity.

The Haemophilia Joint Health Score (HJHS) is a validated physical exam measure of haemophilic arthropathy, used clinically to determine treatment adequacy. Higher scores are worse; however, there is no consensus on a clinically significant score. To establish HJHS reference ranges based on age and haemophilia type and severity, relative to prophylaxis, inhibitor status, annualised bleeding rate and body mass index. This is a cross-sectional analysis of HJHS exams performed between 2012 and 2021 by the University of Colorado Hemophilia and Thrombosis Center in persons with Factor VIII or IX <50%. For each haemophilia type, severity and age group, reference ranges were defined using interquartile ranges, and the percentage of joints with scores overlapping healthy controls were calculated. Univariate and multivariable linear regression determined the influence of modifiers on total HJHS. The association between total HJHS and pain on exam was also evaluated. Initial analysis of all participants showed female and male HJHS values to be statistically different for reasons requiring further investigation; subsequent analyses were limited to males. Multivariable linear regression derived from data on 385 males showed that for each 1-year age increase, total HJHS was 0.5 points higher. Total HJHS were 3.9 points higher in Haemophilia A than Haemophilia B. Ranked haemophilia severity (severe > moderate > mild) incurred 2.4 point increases in total HJHS. Pain was present in 76% of joints with individual joint scores >10. This study quantifies current differences in total HJHS relative to haemophilia type, severity, age and treatment in males.

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2026-02-25 | Socio-Demographic Characteristics of the Hemophilia Patients

Introduction with objective: In Bangladesh, hemophilia patients are not uncommon. Large numbers of haemophilia patients regularly attend in Hemophilia Treatment Center (HTC), Department of Haematology, and Dhaka Medical College Hospital for the management of disease and its complications. The aim of the present study was to assess the socio-demographic characteristics of the hemophilia patients. Materials and Methods: This observational study was carried out among 50 hemophilia patients at the Hemophilia Treatment Center (HTC), Department of Haematology, Dhaka Medical College Hospital (DMCH), and Dhaka from July 2019 to December 2019. Purposive sampling was done according to availability of the patients. All the data were compiled and sorted properly and the quantitative data was analyzed statistically by using Statistical Package for Social Science. Result: Majority of the respondents (38%) were less than or equal 5 years old beside 28% were 6 to 10 years old. 96% respondents were Muslim. 50% patients were unemployed and 46% were students beside only 4% were service holder. 52% patient’s economic status were middle class beside 28% were lower class and 20% were upper class. 92% patients had hemophilia A and 8% had hemophilia B. 68% had mild hemophilia, 24% had moderate and 8% had severe hemophilia. Conclusion: The present study revealed that most of the haemophilia patients belong to a middle socio-economic class, which can interfere their long-term adherence to the expensive therapy. Medicine Today 2026, Vol.38 (1): 82-84

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antibodies

2026-06-01 | Effect of marstacimab in young people living with severe hemophilia A or moderate to severe hemophilia B without inhibitors: A plain language summary from the BASIS study.

What is this summary about? This summary describes a study that looked at how well the study treatment (marstacimab) works in people living with hemophilia. The summary describes how well marstacimab reduced bleeding episodes in young people (adolescents) 12 to 17 years old. Hemophilia is a condition that causes people to bleed more easily because their blood is unable to clot properly. Clotting is when blood turns from liquid into gel to stop bleeding. Hemophilia is caused by not having enough blood clotting factors, which are proteins found in the blood that help in forming a clot and stop bleeding. People living with hemophilia either don't make these proteins, have low amounts of these proteins, or their proteins do not work well. There are different types of hemophilia, depending on which clotting factor is affected. For example, people living with hemophilia A lack clotting factor 8, and people living with hemophilia B lack clotting factor 9. Some treatments for hemophilia work by replacing clotting factors. These treatments are called factor replacement therapy, and are given directly into a vein (called intravenous, or IV for short). They are given frequently, sometimes even more than once a week. In some people living with hemophilia, the body develops antibodies called inhibitors that block replacement clotting factors from working properly. Not all people living with hemophilia produce these antibodies - those who don't are classified as having hemophilia without inhibitors. A different way to treat people living with hemophilia is by using treatment called non-factor replacement therapy. One type of non-factor treatment called marstacimab is given as a regular preventive treatment (called prophylaxis). It works without replacing the missing clotting factors but brings blood clotting and bleeding back to a normal balance. Marstacimab is given once a week as a flat-dose (not based on body weight) injection under the skin (called subcutaneous) using an auto-injector device. This injection is sometimes called a shot and can be easier than injecting directly into a vein. In some cases, marstacimab can be taken less often than clotting factors. Marstacimab offers a new way to treat people living with hemophilia A or B without inhibitors. What were the results of the study? In this study, young people treated with marstacimab for 1 year had on average fewer bleeding episodes than on previous clotting factor replacement treatment. Marstacimab was well tolerated in young people (similar to adults), which means that most side effects that people had were mild to moderate and resolved by the end of the study. What do the results mean? This study showed that a once weekly injection of marstacimab could help reduce bleeding episodes in young people living with hemophilia A or B, without inhibitors.

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2026-04-16 | Expanding the Toolbox With Non-Factor Therapies.

Prophylaxis is the standard of care for people living with haemophilia (PwH) as it is able to prevent majority of bleeding episodes, including joint bleeds and life-threatening bleeds (i.e., intracranial haemorrhage). However, despite undeniable advantages, prophylaxis has limitations including need for frequent intravenous infusions and cost. Adherence to long-term treatment regimens based on multiple weekly intravenous injections of standard half-life products is challenging, and it is highly likely that injections are skipped or delayed with great impact on efficacy due to the rather rapid clearance of the drug from the body. The advent of extended half-life products allowed for greater flexibility and easier treatment personalization with the possibility to improve protection as well as to reduce number of intravenous injections. For people living with haemophilia A and inhibitors the advent of the first non-replacement therapy, emicizumab, made a turning point offering for the first time an effective prophylaxis with the additional advantage of a consistent steady state of haemostatic effect across different ages and body weights and of subcutaneous route of administration. However, during emicizumab prophylaxis breakthrough bleeds might occur due to the limited haemostatic potential which stays in the mild haemophilia range with some interindividual variability and not clearly definable FVIII equivalence. More recently the toolbox for haemophilia care has further expanded with several non-factor therapies that will offer the opportunity of effective prophylaxis to people with haemophilia B with inhibitors, subcutaneous prophylaxis for all PwH and the promise of protection in the non-haemophilia range.

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2025-12-06 | Efficacy and safety of marstacimab prophylaxis in hemophilia A/B with inhibitors: results from the phase 3 BASIS trial.

Marstacimab, a monoclonal antibody that inhibits tissue factor pathway inhibitor, is approved for prophylactic use in individuals with hemophilia A or B without inhibitors. We present efficacy and safety for individuals with inhibitors. The open-label, single-arm, phase 3 study evaluated once-weekly subcutaneous flat-dose marstacimab in males aged 12 to <75 years with severe hemophilia A or moderately severe to severe hemophilia B. Participants with inhibitors received bypassing agents (on-demand or routine prophylaxis) during a 6-month observational phase (OP) before entering a 12-month active treatment phase (ATP) with marstacimab. Primary end points were annualized bleeding rate (ABR) of treated bleeds and safety. Of 60 participants with inhibitors in the OP, 51 entered the ATP and received marstacimab. In the on-demand group (n = 48), mean estimated ABR declined from 19.78 (95% confidence interval [CI], 16.12-24.27) in the OP to 1.39 (95% CI, 0.85-2.29) during the ATP (ABR ratio, 0.07 [95% CI, 0.042-0.118]; 2-sided P< .0001). Results were consistent by hemophilia type (ABR ratio, 0.05 [hemophilia A, n = 40]; 0.13 [hemophilia B, n = 8]). Participants reported significant improvements in health-related quality of life. Adverse events were common but mostly mild; 1 treatment-related grade 3 skin rash led to discontinuation. Antidrug antibodies were detected in 19.6% of participants, with no apparent effect on efficacy or safety. In participants with inhibitors, marstacimab was associated with reduced bleeding rates and an acceptable safety profile, with no thromboembolic events. Marstacimab may be a viable treatment option for people with hemophilia A or B with inhibitors. This trial was registered at www.clinicaltrials.gov as #NCT03938792. ClinicalTrials.gov identifier: NCT03938792.

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2025-10-01 | Significance of ‘Clotting Factors’ in Prosthodontic Treatment Procedures -A Review.

Bleeding disorders and a lack of clotting factors, like hemophilia A (factor VIII deficiency), hemophilia B (factor IX deficiency), von Willebrand disease (VWD), and factor XIII deficiency, make it much harder to do prosthodontic procedures like fixed partial dentures (FPDs) and dental implants because of the risk of too much bleeding, hematoma formation, and delayed healing.These operations entail invasive measures (e.g., tooth preparation, implant osteotomy, or soft tissue manipulation), requiring customized protocols to guarantee hemostasis.Effective management necessitates multidisciplinary collaboration with hematologists, preoperative evaluation (e.g., HEMSTOP questionnaire, factor level testing), and targeted interventions, including factor replacement (to 50-100 IU/dL), desmopressin for mild VWD, antifibrinolytics (e.g., tranexamic acid), and local hemostatic agents (e.g., fibrin glue, gelatin sponges).Recent improvements, such factors with longer half-lives, non-factor therapy (like emicizumab), and flapless implant procedures, make things safer and allow for outpatient care.To reduce difficulties and improve prosthodontic results in these patients, it is important to use atraumatic procedures, preventative dental initiatives, and standardized protocols.

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2025-06-18 | Safety and efficacy of marstacimab in patients with hemophilia A and B: a systematic review and meta-analysis.

Hemophilia A and B are life-threatening congenital bleeding disorders traditionally managed with frequent factor replacement therapies, often complicated by breakthrough bleeds and inhibitor development. Marstacimab, a monoclonal antibody targeting TFPI, has emerged as a novel prophylactic treatment to reduce bleeding episodes in patients without inhibitors. A systematic review was conducted following PRISMA guidelines. A comprehensive literature search was performed across multiple databases. Meta-analysis was conducted using R, applying a random-effects model. Nine manuscripts were included. Marstacimab significantly reduced the annualized bleeding rate (mean difference: -16.30; 95% CI: [-18.46, -14.15], p < 0.001) and showed a favorable safety profile with most adverse events being mild or moderate, and no thrombotic events reported. The use of a prefilled pen device further highlighted the therapeutic benefits and ease-of-use of Marstacimab. This meta-analysis reinforces the efficacy and safety of Marstacimab in reducing bleeding rates in severe hemophilia A and B. The findings support its role as a promising, transformative alternative to conventional factor replacement therapies. The study protocol for this systematic review was registered in the International Prospective Registry of Systematic Reviews (PROSPERO) database (www.crd.york.ac.uk/prospero/), and it was allocated the PROSPERO identification number CRD42024620215.

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2026-01-09 | Molecular mechanisms and therapeutic strategies for the recurrent F9 (c.520 + 13 A > G) variant in hemophilia B.

Hemophilia B (HB), an X-linked recessive disorder, results from variants in the coagulation factor IX gene (F9). The F9 c.520 + 13 A > G variant is a recurrent intronic variant in HB patients, accounting for 15.05% of all documented F9 intronic variants. Despite prior predictions of its impact, the molecular mechanism associated with moderate to mild HB remains undissected. In silico predictions and splicing-competent cDNA constructs were used to assess the impact of F9 c.520 + 13 A > G on mRNA splicing. Factor IX (FIX) variant (p.V174delinsGHNLM) expression in HEK293T cells was evaluated using activated partial thromboplastin time, enzyme-linked immunosorbent assay, Western blot analysis, and immunofluorescence analyses. Structural modeling and molecular dynamics simulations were performed to evaluate the structural impact of the variant. Engineered U1 small nuclear RNA (U1snRNA) was challenged with F9 full-length splicing-competent constructs to evaluate splicing correction. The F9 c.520 + 13 A > G variant caused nearly complete aberrant splicing, producing the F9 c.520_521insGTCATAATCTGA insertion and the in-frame FIX p.V174delinsGHNLM variant. A small amount (approximately 10%) of wild-type FIX was also detected. We characterize the p.V174delinsGHNLM variant, which exhibited impaired secretion and increased intracellular accumulation. Interestingly, an engineered U1snRNA partially rescued aberrant splicing, restoring functional FIX levels to approximately 40%. This study elucidates the molecular mechanism of the F9 c.520 + 13 A > G variant, which activates a cryptic 5' splice site in intron 5, leading to an in-frame FIX (p.V174delinsGHNLM) with secretion defects and loss of protein function. And Engineered U1snRNA partially rescued the splicing defect.

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2025-12-29 | Rebalancing Hemostasis: Fitusiran as a First‐in‐Class RNAi Therapy in Hemophilia A and B

Background and Aims: Fitusiran is a first-in-class RNA interference (RNAi) therapy that lowers antithrombin (AT) to rebalance hemostasis in people with Hemophilia A or B, with or without inhibitors. Its recent FDA approval marks a major shift toward factor-independent prophylaxis. This commentary aims to summarize the clinical evidence supporting fitusiran, highlight its therapeutic significance, and discuss its potential advantages and safety considerations. Methods: This commentary reviews key findings from Phase 1-3 clinical trials, including ATLAS-INH and ATLAS-PPX, as well as regulatory documents and published pharmacologic evaluations. Evidence on annualized bleeding rate (ABR) reduction, thrombin generation, safety outcomes, and patient-reported benefits was synthesized to assess the impact of AT suppression on bleed prevention. Results: Across clinical development, fitusiran produced substantial reductions in bleeding rates in Hemophilia A and B, irrespective of inhibitor status. Phase 1 and 2 trials demonstrated > 70%-80% AT suppression with marked increases in thrombin generation. In Phase 3 trials, median ABR decreased from 17.7 to 0.0 in ATLAS-INH and by approximately 65% in ATLAS-PPX after switching from standard prophylaxis. Many participants remained completely bleed-free. Safety findings included reversible elevations in liver enzymes, mild injection-site reactions, headaches, and rare thrombotic events, necessitating AT-level and hepatic monitoring. Conclusion: Fitusiran offers a transformative, once-monthly prophylactic option with broad applicability across hemophilia types and inhibitor status. Its RNAi-based, factor-independent mechanism enables durable bleed protection and improved treatment convenience. While long-term hepatic safety and thrombotic risk require continued surveillance, fitusiran represents a significant advance in hemophilia management and a promising step toward more accessible, individualized, and rebalancing-based therapies.

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2020-08-03 | Pathological mechanism and antisense oligonucleotide-mediated rescue of a non-coding variant suppressing factor 9 RNA biogenesis leading to hemophilia B.

Loss-of-function mutations in the human coagulation factor 9 (F9) gene lead to hemophilia B. Here, we dissected the consequences and the pathomechanism of a non-coding mutation (c.2545A>G) in the F9 3' untranslated region. Using wild type and mutant factor IX (FIX) minigenes we revealed that the mutation leads to reduced F9 mRNA and FIX protein levels and to lower coagulation activity of cell culture supernatants. The phenotype could not be compensated by increased transcription. The pathomechanism comprises the de novo creation of a binding site for the spliceosomal component U1snRNP, which is able to suppress the nearby F9 poly(A) site. This second, splicing-independent function of U1snRNP was discovered previously and blockade of U1snRNP restored mutant F9 mRNA expression. In addition, we explored the vice versa approach and masked the mutation by antisense oligonucleotides resulting in significantly increased F9 mRNA expression and coagulation activity. This treatment may transform the moderate/severe hemophilia B into a mild or subclinical form in the patients. This antisense based strategy is applicable to other mutations in untranslated regions creating deleterious binding sites for cellular proteins.

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2017-09-12 | Targeting of Antithrombin in Hemophilia A or B with RNAi Therapy.

Current hemophilia treatment involves frequent intravenous infusions of clotting factors, which is associated with variable hemostatic protection, a high treatment burden, and a risk of the development of inhibitory alloantibodies. Fitusiran, an investigational RNA interference (RNAi) therapy that targets antithrombin (encoded by SERPINC1), is in development to address these and other limitations. In this phase 1 dose-escalation study, we enrolled 4 healthy volunteers and 25 participants with moderate or severe hemophilia A or B who did not have inhibitory alloantibodies. Healthy volunteers received a single subcutaneous injection of fitusiran (at a dose of 0.03 mg per kilogram of body weight) or placebo. The participants with hemophilia received three injections of fitusiran administered either once weekly (at a dose of 0.015, 0.045, or 0.075 mg per kilogram) or once monthly (at a dose of 0.225, 0.45, 0.9, or 1.8 mg per kilogram or a fixed dose of 80 mg). The study objectives were to assess the pharmacokinetic and pharmacodynamic characteristics and safety of fitusiran. No thromboembolic events were observed during the study. The most common adverse events were mild injection-site reactions. Plasma levels of fitusiran increased in a dose-dependent manner and showed no accumulation with repeated administration. The monthly regimen induced a dose-dependent mean maximum antithrombin reduction of 70 to 89% from baseline. A reduction in the antithrombin level of more than 75% from baseline resulted in median peak thrombin values at the lower end of the range observed in healthy participants. Once-monthly subcutaneous administration of fitusiran resulted in dose-dependent lowering of the antithrombin level and increased thrombin generation in participants with hemophilia A or B who did not have inhibitory alloantibodies. (Funded by Alnylam Pharmaceuticals; ClinicalTrials.gov number, NCT02035605 .).

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2011-11-01 | RNA‐based therapeutic approaches for coagulation factor deficiencies

SummarySubstitutive therapy has significantly ameliorated the quality of life of patients with coagulation factor deficiencies. However, there are some limitations that support research towards alternative therapeutic approaches. Here we focus on the rescue of coagulation factor biosynthesis by targeting the RNA processing and translation, which would permit restoration of the altered gene expression while maintaining the gene regulation in the physiological tissues. The essential prerequisite of the three reported RNA‐based correction approaches (i–iii), which rely on mutation types and are applicable even to large size mRNAs, is the presence in cells of the precursor (pre‐mRNA) or mature mRNA forms. (i) In the F7 gene, modification of the small nuclear RNA U1 (U1 snRNA), the key component of the spliceosomal U1 ribonucleoprotein, re‐directs correct usage of a mutated exon–intron junction, triggering synthesis of correct mRNA and secretion of functional factor (F)VII. (ii) Spliceosome‐mediated RNA trans‐splicing (SMaRT) between mutated and engineered pre‐mRNAs produces normal FVIII mRNA and secretion of functional protein. (iii) Aminoglycoside drugs induce ribosome readthrough and suppress premature translation termination caused by nonsense mutations in FVII, VIII and IX. The rescued expression levels ranged from very low (aminoglycosides) to moderate (U1 snRNA and SMaRT), which could result in amelioration of the disease phenotypes. These findings prompt further studies aimed at demonstrating the clinical translatability of RNA‐based strategies, which might open new avenues in the treatment of coagulation factor deficiencies. Substitutive therapy has significantly ameliorated the quality of life of patients with coagulation factor deficiencies. However, there are some limitations that support research towards alternative therapeutic approaches. Here we focus on the rescue of coagulation factor biosynthesis by targeting the RNA processing and translation, which would permit restoration of the altered gene expression while maintaining the gene regulation in the physiological tissues. The essential prerequisite of the three reported RNA‐based correction approaches (i–iii), which rely on mutation types and are applicable even to large size mRNAs, is the presence in cells of the precursor (pre‐mRNA) or mature mRNA forms. (i) In the F7 gene, modification of the small nuclear RNA U1 (U1 snRNA), the key component of the spliceosomal U1 ribonucleoprotein, re‐directs correct usage of a mutated exon–intron junction, triggering synthesis of correct mRNA and secretion of functional factor (F)VII. (ii) Spliceosome‐mediated RNA trans‐splicing (SMaRT) between mutated and engineered pre‐mRNAs produces normal FVIII mRNA and secretion of functional protein. (iii) Aminoglycoside drugs induce ribosome readthrough and suppress premature translation termination caused by nonsense mutations in FVII, VIII and IX. The rescued expression levels ranged from very low (aminoglycosides) to moderate (U1 snRNA and SMaRT), which could result in amelioration of the disease phenotypes. These findings prompt further studies aimed at demonstrating the clinical translatability of RNA‐based strategies, which might open new avenues in the treatment of coagulation factor deficiencies.

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