Cedric Hermans

• MD, PhD, FRCP (Lon, Edin)
• Head of Department at Catholic University of Louvain

Introduction Gene editing therapies offer the possibility of substantial improvement in treatment and quality of life for people with haemophilia (PWH) in a landscape of dynamic therapeutic advancement. Developing a common and understandable language to discuss gene editing will be essential to ensure these treatments can be deployed in a safe and...

Introduction Eptacog beta is a novel human recombinant FVIIa approved for use in the United States, European Union, United Kingdom and Mexico for the treatment and control of bleeding in patients with haemophilia A or B with inhibitors (≥12 years). It is also indicated for perioperative care in the same patient population in Europe and the United K...

Introduction The 2024 ISTH clinical practice guideline (CPG) for treatment of congenital haemophilia, the NBDF‐McMaster Guideline on Care Models for Haemophilia Management, and ASH ISTH NBDF WFH guidelines on the diagnosis and management of VWD all utilised GRADE methodology. Aim Discuss missed opportunities and the methodological approach of the...

Introduction Evidence‐based clinical practice guidelines drive optimal patient care and facilitate access to high‐quality treatment. Creating guidelines for rare diseases such as haemophilia, where evidence does not often come from randomized controlled trials but from non‐randomized and well‐designed observational studies and real‐world data, is c...

Management of bleeding in persons with hemophilia and inhibitors involves treatment with bypassing agents, including recombinant activated factor VII (rFVIIa). Two rFVIIa products are commercially approved for use in the United States and the European Union. Eptacog alfa and eptacog beta share the same amino acid sequence but differ in posttranslat...

Introduction Joint and muscle bleeds cause acute pain in persons with hemophilia (PwH). Assessment of pain by PwH and their providers is important in guiding the management of bleeding episodes (BEs), as the onset of acute pain often signals the start of joint or soft tissue BEs and the need for treatment. In addition, pain relief can indicate blee...

The treatment landscape of hemophilia has been evolving rapidly over the past few decades. One of these innovations is emicizumab (Hemlibra®), a bispecific antibody mimicking the cofactor activity of coagulation Factor VIII (FVIII). Unlike classical replacement therapy with FVIII concentrates, emicizumab is administered subcutaneously on a weekly b...

Introduction D-dimer testing plays a crucial role in the diagnostic strategy of venous thromboembolic disease (VTED) and the decision of initiating anticoagulation. It is also used to determine the duration of anticoagulation and to predict recurrent VTED after stopping anticoagulant therapy for unprovoked VTED. Whether the D-dimer (DD) concentrati...

Congenital hemophilia A (HA) disease severity has traditionally been categorized according to intrinsic factor (F)VIII levels, with <1% of normal indicating severe HA, 1% to 5% moderate HA, and 6% to 40% mild HA. However, mounting evidence illustrates considerable variability in bleeding phenotype regardless of FVIII level. Despite treatment advanc...

Introduction Despite the progress in gene editing platforms like CRISPR/Cas9 with the potential to transform the standard of care for haemophilia, the language used to explain and discuss gene editing is not aligned across the haemophilia community. Here, we present the objective and rationale for developing a clear, consistent, and globally aligne...

Over recent decades, management of people with hemophilia (PwH) has been greatly improved by scientific advances that have resulted in a rich and varied therapeutic landscape. Nevertheless, treatment limitations continue to drive innovation, and emerging options have the potential to realize further improvement. We advocate four general principles...

Despite numerous efforts to raise awareness, many hemophilia carriers and female persons with hemophilia (PWHs) remain undiagnosed. Between May 2021 and April 2023, we identified potential and obligate carriers of hemophilia A (HA) and B (HB) by updating pedigrees of all PWHs followed at the Cliniques universitaires Saint-Luc, Brussels. Retrospecti...

Background Treatment options for people with haemophilia are evolving at a rapid pace and a range of prophylactic treatment options using various technologies are currently available, each with their own distinct safety and efficacy profile. Treatment goals The access to replacement therapy and prophylaxis has driven a dramatic reduction in mortal...

Background People with hemophilia often experience pain and suffer from comorbidities related to their bleeding disorder. Consequently, unemployment due to disability is prevalent among people with hemophilia. Objectives To explore associations between unemployment due to disability and treatment while adjusting for known risk factors for unemploy...

Background Patients with hemophilia have a life-long risk of developing neutralizing antibodies (inhibitors) against clotting factor concentrates. After the first 50 exposure days (EDs), ie, in previously treated patients (PTPs), data on inhibitor development are limited. Objectives To report inhibitor development according to factor (F)VIII or FI...

Introduction Valoctocogene roxaparvovec, a gene therapy evaluated in the phase 3 GENEr8‐1 trial, supports endogenous factor VIII (FVIII) production to prevent bleeding in people with severe haemophilia A. Individuals receiving emicizumab, an antibody mimicking the function of activated FVIII, were excluded from GENEr8‐1 enrolment since emicizumab w...

Objective The objective of this study is to assess the reliability and construct validity of ACTIVLIM‐Hemo, a newly developed Rasch‐built questionnaire designed to evaluate activity limitations in people with haemophilia (PwH), in comparison with the Haemophilia Activities List (HAL), which was developed using Classical Test Theory. Methods A tota...

Introduction Considering the advances in haemophilia management and treatment observed in the last decades, a new set of value‐based outcome indicators is needed to assess the quality of care and the impact of these medical innovations. Aim The Value‐Based Healthcare in Haemophilia project aimed to define a set of clinical outcome indicators (COIs...

Eptacog beta (activated), a recombinant human factor VIIa (rFVIIa), was approved by the US Food and Drug Administration (FDA) in 2020 (SEVENFACT®, LFB & HEMA Biologics) and the European Medicines Agency (EMA) in 2022 (CEVENFACTA®, LFB). In Europe, eptacog beta is indicated for the treatment of bleeds and the prevention of bleeds during surgery or i...

Background Emicizumab, a bispecific monoclonal antibody, bridges activated factor (F) IX and FX, mimicking the function of missing or deficient activated FVIII in people with hemophilia A (HA). Objectives To evaluate the long-term efficacy and safety of emicizumab prophylaxis in people with HA without FVIII inhibitors in the HAVEN 3 and 4 studies....

Introduction Persons with hemophilia A or B and inhibitors (PwHABI) who are not on prophylaxis may have high rates of bleeding, and, if not treated effectively, may have significant morbidity related to rebleeding. Dosing strategies of bypassing agents (BPAs) are variable in clinical practice, and following a period of initial bleed control, reblee...

Introduction Elderly people with haemophilia (PwH) develop haemophilic arthropathy, pain, and reduced health‐related quality of life (HR‐QoL). The condition of elderly mild haemophilia patients have rarely been evaluated. This study aimed to compare joint status, pain, and HR‐QoL between elderly with mild, moderate/severe haemophilia and healthy el...

Background Hemophilia A (HA) is predominantly associated with males due to X-linked inheritance. Males and females with HA have shared unmet medical needs, highlighting the necessity for comprehensive care irrespective of sex. Objectives This analysis investigated the efficacy and safety of emicizumab prophylaxis in 3 females with HA. Methods HAV...

In people with haemophilia (PwH), joint pain is a major comorbidity that is often overlooked and under-treated. It is believed that, to ensure the most successful outcome, pain management should be tailored to the predominant pain phenotype (i.e., nociceptive, neuropathic and nociplastic). The 2021 clinical criteria and grading system for nociplast...

Introduction: With the increasing complexity of haemophilia care and the advent of numerous therapeutic innovations, there is an unmet need for documentation and data collection tools tailored to people with haemophilia (PwH). To date, no fully integrated haemophilia-specific electronic health record (EHR) has been described in the literature. Ai...

COVID-19 is associated with an increased risk for thrombotic complications. The trials investigating the optimal thromboprophylactic dose are performed in challenging times and seemingly produce conflicting evidence. The burdensome circumstances, divergent endpoints, and different analytical approaches hamper comparison and extrapolation of availab...

Background: Joint pain is the hallmark of haemophilia; therefore it seems clinically rather a musculoskeletal than a bleeding disorder. Although joint pain in people with haemophilia (PwH) is a complex and multidimensional problem, pain assessment remains primarily focused on the structural evaluation of their joints. Whereas, only few data are av...

Background The bypassing agent, activated prothrombin complex concentrate [aPCC, FEIBA (factor VIII inhibitor bypass activity); Baxalta US Inc, a Takeda company, Lexington, MA, USA], is indicated for the treatment of bleeding episodes, perioperative management, and routine prophylaxis in patients with hemophilia A or B with inhibitors. In certain c...

Transplant-associated endothelial complication (TA-EC) are life-threatening complications after allogeneic hematopoietic cell transplantation (alloHCT) and include thrombotic microangiopathy, systemic and pulmonary syndromes. There is no validated biomarker to predict them. We conducted a retrospective study to assess the role of von Willebrand fac...

Background Advances in treatment have enabled patients with haemophilia A to live longer and therefore may be subjected to comorbidities associated with ageing, in addition to disease-associated morbidities. There have been few reports to date on efficacy and safety of treatment specifically in patients with severe haemophilia A and comorbidities....

Recent advances in therapeutics are now providing a wide range of options for adults and children living with hemophilia. Although therapeutic choices are also increasing for the youngest individuals with severe disease, challenges remain about early management decisions, as supporting data are currently limited. Parents and healthcare professional...

Introduction: Pain is highly prevalent in people with haemophilia (PwH), especially in those who did not receive adequate early prophylaxis. Despite the multifactorial aetiology of pain, its evaluation in PwH is commonly restricted to the evaluation of joint-related pain. Therefore, this study aimed at presenting a psychophysical assessment of pain...

Background: Clinical trial data are scarce for the use of prophylaxis in people with non-severe haemophilia A. The HAVEN 6 study aims to assess safety and efficacy of emicizumab prophylaxis in people with non-severe haemophilia A without factor VIII (FVIII) inhibitors. Methods: HAVEN 6 is a multicentre, open-label, single-arm, phase 3 study taki...

Introduction: People with haemophilia (PwH) suffer from knee and ankle joint pain, but the association with structural damage remains underexplored. They report activity limitations but it is unclear which factors contribute to lower limb activity limitations (LL-AL). Aims: This study aimed (i) to analyse the association between ankle joint pain...

Introduction: Pain is a major issue in people with haemophilia (PwH). Few studies comprehensively assessed pain in PwH using a biopsychosocial framework and studies in mild PwH are lacking. Aim: To assess pain prevalence, pain interference and their relationship with health-related quality of life (HR-QoL) in male adults with haemophilia. Metho...

Gene-based therapy opens an entirely new paradigm in managing people with haemophilia (PWH), offering them the possibility of a functional cure by enabling continuous expression of factor VIII (FVIII) or factor IX (FIX) after transfer of a functional gene designed to replace the PWH's own defective gene. In recent years, significant advances in gen...

Background: Hemophilia management has fundamentally evolved over the last decades with the development of ground-breaking therapies. Because of their mode of action and biochemical properties, these innovative therapies that are available in developed countries could be readily implemented among people from low-income countries who are either not...

Introduction: To assess activity limitations in people with haemophilia (PwH), the self-reported Haemophilia Activity List (HAL) is widely employed, despite several methodological limitations impacting the interpretation of categorical scores. Modern psychometric approaches avoid these limitations by using a probabilistic model, such as the Rasch...

Background: The optimal duration of antithrombotic therapy (ATT) after patent foramen ovale (PFO) closure remains under debate. This study sought to compare the clinical outcome of patients receiving antithrombotic agents for a short (6 months) versus extended (>6 months) period after the procedure. Methods: This was a retrospective cohort study...

Introduction: As people with haemophilia (PWH) receive better treatment and live longer they are more likely to encounter cardiovascular disease (CVD) and other comorbidities. ESC guidelines for the acute management of patients presenting with acute coronary syndrome (ACS) are based on the non-haemophilia population. Aim: To review the guideline...

The World Federation of Haemophilia (WFH) is a global network of national member organizations (NMOs) that advocate, collectively and individually, to improve lives of people with inherited bleeding disorders. The WFH vision of "Treatment for All" speaks to a future in which all people with an inherited bleeding disorder will have access to care, r...

Introduction: Despite the fact that joint bleeds (haemarthrosis) frequently occur in people with haemophilia (PwH) with invalidating arthropathies as result, the clinical pain experience has received only limited attention. A sudden increase in pain intensity can be linked to a bleed, but in most cases, no acute bleed is confirmed. Nevertheless, a...

Background: Mild haemophilia (MH) is mainly characterized by haemorrhages secondary to surgery/invasive procedures or trauma. Haemostatic treatment in MH ranges from on demand to short prophylaxis according to the type of bleeding events and the basal clotting factor level. Oral surgery and dental extractions can represent a frequent haemostatic c...

Great multidisciplinary experience for the team of the University of Antwerp and UCLouvain during the World Federation of Haemophilia congress. Nathalie Roussel and Valérie-Anne Chantrain were invited to speak on the necessity of implementing the biopsychosocial model to pain in men with haemophilia and women with bleedings disorders. The interplay...

New treatment possibilities and modalities are now available globally for patients with haemophilia requiring surgery or invasive procedures. The first is the appropriate application of low‐dose protocols of clotting factor concentrates (CFC) achieving adequate perioperative haemostasis in resources constraint environments. The increasing availabil...

Haemophilia B is a rare X-linked genetic deficiency of coagulation factor IX (FIX) that, if untreated, can cause recurrent and disabling bleeding, potentially leading to severe arthropathy and/or life-threatening haemorrhage. Recent decades have brought significant improvements in haemophilia B management, including the advent of recombinant FIX an...

This review compares the methodology of published clinical studies investigating the extended-half-life (EHL) factor VIII (FVIII) products, rFVIIIFc (efmoroctocog alfa, Elocta®/Eloctate®), BAY 94-9027 (damoctocog alfa pegol, Jivi®), BAX 855 (rurioctocog alfa pegol, Adynovate®) and N8-GP (turoctocog alfa pegol, Esperoct®) including the phase 2/3 stu...

Introduction: Eptacog beta is a new recombinant activated human factor VII bypassing agent approved in the United States for the treatment and control of bleeding in patients with haemophilia A or B with inhibitors 12 years of age or older. Aim: To prospectively assess in a phase 3 clinical trial (PERSEPT 2) eptacog beta efficacy and safety for...

Introduction: Ankle arthropathy is highly prevalent among people with haemophilia (PwH), even with prophylaxis, and leads to pain and disability. Mechanisms and consequences of painful symptoms related to ankle arthropathy have not been extensively studied. Methods: A consecutive sample of 30 adult PwH was included (60 ankles). Ankle structure w...

Hemophilia B is a bleeding disorder caused by a deficiency of coagulation factor IX (FIX). Treatment with FIX replacement products can increase FIX activity levels to minimize or prevent bleeding events. However, frequent dosing with standard-acting FIX products can create a high treatment burden. Long-acting products have been developed to maintai...

Introduction: Many people with haemophilia (PwH) report invalidating ankle pain. As the ankle is a weight bearing joint, its role in daily functioning is extremely important. While some studies investigated alterations in structure in the talocrural joint (TCJ), studies assessing the subtalar joint (STJ) are lacking and ankle pain in PwH is only po...

Background: The Hemophilia Joint Health Score (HJHS) was developed and validated to detect arthropathy in children. Additional evidence is required to show validity in adults. We studied the convergent and discriminant construct validity of the HJHS version 2.1(HJHSv2.1) in adults with hemophilia. A secondary aim was to define age-related normativ...

Introduction Following treatment with a bypassing agent, parents or caregivers often face difficulties in determining bleeding episode (BE) resolution in children with hemophilia A or B and inhibitors (CwHABI), potentially contributing to a longer treatment duration in children as compared to adults (Valentino et al, Haemophilia 2012; 18:554-60. Gr...

Background: Emicizumab, a bispecific monoclonal antibody, bridges activated factor (F)IX and FX, substituting for the function of missing activated FVIII in persons with hemophilia A (HA). The HAVEN 6 study (NCT04158648) aims to assess the safety, efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) of emicizumab prophylaxis in persons with m...

The cover image is based on the Original Article The safety of activated eptacog beta in the management of bleeding episodes and perioperative haemostasis in adult and paediatric haemophilia patients with inhibitors by Miguel Escobar et al., https://doi.org/10.1111/hae.14419.

Introduction: Haemophilia patients with inhibitors often require a bypassing agent (BPA) for bleeding episode management. Eptacog beta (EB) is a new FDA-approved recombinant activated human factor VII BPA for the treatment and control of bleeding in haemophilia A or B patients with inhibitors (≥12 years of age). We describe here the EB safety prof...

Introduction: Surgical procedures in persons with haemophilia A or B with inhibitors (PwHABI) require the use of bypassing agents (BPA) and carry a high risk of complications. Historically, only two BPAs have been available; these are reported to have variable responses. Aim: To prospectively evaluate the efficacy and safety of a new bypassing a...

Introduction: A second peak of inhibitors has been reported in patients with severe haemophilia A (HA) aged >50 years in the UK.1 The reason for this suggested breakdown of tolerance in the ageing population is unclear, as is the potential impact of regular exposure to the deficient factor by prophylaxis at higher age. No data on haemophilia B (HB...

The mainstay of hemophilia treatment is to prevent bleeding through regular long-term prophylaxis and to control acute breakthrough bleeds. Various treatment options are currently available for prophylaxis, and treatment decision-making is a challenging and multifaceted process of identifying the most appropriate option for each patient. A multidis...

A man with severe hemophilia A (HA) without factor VIII (FVIII) inhibitors was admitted for total arthroplasty of his elbow. The patient was being treated with emicizumab, with his last administration given 8 days before surgery. Preoperatively, he received a bolus of 4000 international units (IU) of recombinant (r)FVIII. Throughout the operation,...

Background: Emicizumab, a bispecific monoclonal antibody administered subcutaneously, mimicking the action of activated coagulation factor VIII, has been approved in Europe for use in patients with severe hemophilia of all ages. Aims: To assess availability, acceptance, adverse events, efficacy and laboratory monitoring of emicizumab and the effec...

Despite the numerous and groundbreaking therapeutic advances made in the field of hemophilia over the past decades and particularly in recent years, hemophilia remains a disease that has a major impact on the daily lives of our patients, through the multiple complications and burdensome treatments it imposes. The disease burden is not only physical...

The physiotherapist plays an essential role for people with haemophilia, an inherited bleeding disease responsible for musculoskeletal complications. Yet, with the advent of new and advanced therapies, the medical landscape is changing, and physiotherapy must adapt alongside. This paper considers whether there will still be a need for physiotherapy...

Background Non-severe hemophilia A patients have a life-long inhibitor risk. Yet, no studies analyzed risk factors for inhibitor development after 50 factor VIII (FVIII) exposure days (EDs). Objectives This case-control study investigated treatment-related risk factors for inhibitor development in non-severe hemophilia A and assessed whether these...

The classical goals of haemophilia A treatment are to prevent bleeds, minimise the risk of long-term complications associated with joint damage, and improve quality of life by maintaining appropriate factor VIII [FVIII] levels. The dose and frequency of FVIII replacement therapies required to reduce bleeds is now known to vary amongst individuals,...

Background Hemophilia is an X-linked hereditary bleeding disorder caused by deficiency in coagulation and a tendency for bleeding in muscles and large synovial joints (i.e. elbows, knees and ankles). Intra-articular bleeding (hemarthrosis) causes synovial hypertrophy and cartilage damage, with gradual but inexorable joint destruction (hemophilic ar...

New therapeutic agents for haemophilia with inhibitors that are in development or already licensed are expected to provide transformative treatment options. Many of these new therapies are not based on simply replacing the missing factor; new strategies include bispecific antibody technology that mimics factor VIII coagulation function (emicizumab)...

Objective To establish clear priorities for the care of patients with acquired hemophilia A (AHA) by proposing 10 key principles of practical, holistic AHA management. Method These principles were developed by the Zürich Haemophilia Forum, an expert panel of European hemophilia specialists comprising physicians and nursing and laboratory specialis...

Background: While the number of individuals with hemophilia who are expected to be or have already been included in gene therapy trials has been regularly reported, the number of unscreened or excluded individuals, in addition to the reasons for ex-clusion, is mostly not reported. Methods: We conducted an eligibility assessment of all people with...

Direct oral anticoagulants (DOACs) are widely used in several indications, but data on their efficacy and safety in individuals affected by severe inherited thrombophilia, yet without any personal history of thrombosis, is lacking. Severe inherited thrombophilia abnormalities, especially antithrombin deficiency, confer a higher risk of developing v...

Introduction: Chronic pain related to haemophilic arthropathy is a major concern in patients with haemophilia (PwH) and impacts their quality of life (QoL). At the present time, the majority of studies dedicated to pain assessment in haemophilia evaluated mainly severe and moderate PwH. Instead, this study focuses on two PwH subgroups that are negl...

Introduction In sub‐Saharan Africa, access to clotting factor concentrates (CFCs) is often extremely limited and published data on people with haemophilia on prophylaxis are almost not existent. Aims and Methods To assess the feasibility, barriers and outcomes of a low‐dose and low‐frequency prophylaxis with extended half‐life (EHL) recombinant Fc...

Background: Etranacogene dezaparvovec is an investigational gene therapy for hemophilia B (HB) comprising an adeno-associated virus serotype 5 (AAV5) vector containing a codon-optimized Padua variant human factor IX (FIX) gene with a liver specific promoter. In a Phase 2b study, a single dose of etranacogene dezaparvovec provided mean FIX activity...

Introduction Eptacog beta [Sevenfact®, coagulation factor VIIa (recombinant)-jncw] (HEMA Biologics and LFB) is a human rFVIIa variant indicated for the treatment and control of bleeding events (BEs) in adults and adolescents with hemophilia A or B with inhibitors. Eptacog beta has not yet been approved for perioperative management; therefore, a pha...

Introduction Joint bleeding events (BEs) have cumulative, irreversible and debilitating consequences for persons with hemophilia A or B with inhibitors (PwHABI) due to synovitis and joint iron deposition. To limit the long-term consequences of bleeding into joints, early bleed resolution is a primary treatment goal. Eptacog beta (Sevenfact®, HEMA B...

Introduction Eptacog beta [Sevenfact®, coagulation factor VIIa (recombinant)-jncw] (HEMA Biologics and LFB) is a human rFVIIa variant indicated for the treatment and control of bleeding events (BEs) in adults and adolescents with hemophilia A or B and inhibitors. In a phase 3 clinical trial (PERSEPT 1, NCT02020369) two initial dose regimens of epta...

Introduction and Objective: Development of inhibitory antibodies is a major complication of factor replacement therapy in patients with congenital hemophilia A or B. The FEIBA Global Outcome study (FEIBA GO) assessed the long-term safety and real-world effectiveness of activated prothrombin complex concentrate (aPCC; Baxalta US Inc, a Takeda compan...

Clinical significance of distal deep vein thrombosis (DVT) is important as it can potentially result in pulmonary embolism (PE), DVT extension, DVT recurrence and post-thrombotic syndrome (PTS). Controversy remains about the necessity and modalities of anticoagulation in all distal DVT. Evaluation of the efficiency of a 40-day weight-based low mole...

Background Deep venous thrombosis (DVT) is a common postoperative complication in patients undergoing major orthopaedic surgery of the lower limbs, such as total hip or knee replacement (THR, TKR). Routine pharmacological thromboprophylaxis with low‐molecular‐weight heparin (LMWH) or a direct oral anticoagulant agent is strongly recommended in this...

Prophylactic therapy with exogenous clotting factor concentrates in haemophilia A and B aims to achieve levels of circulating FVIII or FIX that are adequate for the prevention or reduction of spontaneous joint bleeding. Historically, a minimum trough level of at least 1% of the normal levels of circulating clotting factor has been targeted using st...