Evaluation of an e-Learning Program for Community Pharmacists for Dispensing Emicizumab (Hemlibra) in France: Nationwide Cross-Sectional Study.

BACKGROUND: Since June 2021, patients with hemophilia A with antifactor VIII inhibitors and those with severe hemophilia A without antifactor VIII inhibitors treated with Hemlibra have had to choose between a community or hospital pharmacy. The French reference center for hemophilia developed the HEMOPHAR e-learning program for community pharmacists for dispensing emicizumab. OBJECTIVE: This study aims to evaluate the efficiency and safety of this new care pathway by assessing the HEMOPHAR e-learning program. METHODS: The methodology is based on Kirkpatrick's model for evaluating the immediate reaction of trained community pharmacists (level 1), their level of acquired knowledge (level 2), and their professional practice after 3 months of dispensation (level 3). RESULTS: The HEMOPHAR e-learning program reached a large audience, with 67% (337/502) of the eligible community pharmacists following it. The immediate reaction was overall satisfying. High rates of engagement were reported with 63.5% (214/337) to 73.3% (247/337) of completed training modules, along with high rates of success with quizzes of 61.5% (174/337) to 95.7% (244/337). We observed that 83.9% (193/230) of the community pharmacists needed less than 2 attempts to pass the quiz of the module related to professional practice, while the other quizzes required more attempts. Advice on compliance and drug interactions were most frequently provided to patients by the community pharmacists. CONCLUSIONS: This study suggests ways to improve the training of community pharmacists and to optimize coordination with treatment centers. This study also reports on the feasibility of switching to a community pharmacy in a secure pharmaceutical circuit, including in the context of a rare bleeding disease. TRIAL REGISTRATION: ClinicalTrials.gov NCT05449197; https://clinicaltrials.gov/study/NCT05449197. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/43091.

Perspectives and perception of haemophilia gene therapy by French patients.

INTRODUCTION AND AIM: A national survey was initiated by representatives of French patients with haemophilia (AFH) and the French reference centre for haemophilia, in order to appreciate the awareness and knowledge of these patients regarding haemophilia gene therapy (HGT) and understand better their position about this innovative treatment that will soon become available. RESULTS: Of 143 answers received, 137 could be analysed, representing about 3.5% of patients with severe or moderate haemophilia over 16year-old. They were 80.3% with haemophilia A and 19.7 % with haemophilia B, with a severe form of the disease for 80.3 % of them. Curiosity for HGT was formulated by 64.2% of the participants, 33.6 % being interested by this approach as soon as it will be available and 38.7 % preferring to wait until more patients have been treated. Only 3.6 % of the participants would never consider receiving HGT. The level of awareness and knowledge was estimated to be limited by 39.5 % of the patients. More than 60 % of them declared having never or almost never discussed HGT with the team of their haemophilia centre. Before deciding to get HGT, 54.4 % of the participants considered that it will be very important to compare it with their current treatment and 53.7 % would like to be better informed by their care providers. CONCLUSIONS: These results highlight the need for training and education for patients, but also for professionals at haemophilia centres, about HGT and the shared decision-making process. Objective, unbiased and transparent information must be available for patients about this very promising therapy which nonetheless carries more uncertainty and unknowns compared to other haemophilia treatments.

A single-centre experience of 29 total ankle replacement in haemophiliac patients: Therapeutic management, factor consumption and cost.

INTRODUCTION: In patients with haemophilia, repeated bleeding in large joints leads to chronic haemophilic arthropathy, a rare disease that can be managed surgically with ankle arthrodesis or with total ankle replacement (TAR). TAR has been reported to provide good surgical results in the medium/long-term and allow preservation of joint mobility but the medical therapeutic management of the patients has not been described. AIM: To describe the medical therapeutic management of TAR. METHODS: All patients with haemophilia A/B, with haemophilic ankle arthropathy, and who underwent TAR between April 2006 and October 2019 were retrospectively included. Factor consumption, perioperative and early complications, volume of blood lost, and orthopaedic data were collected. RESULTS: A total of 25 patients underwent 29 TAR (mean age was 44.7 years [range: 26-65]). In the 17 patients with HA without history of anti-FVIII inhibitor, the mean ± SD consumption the day of surgery was 116 ± 16 UI/kg when clotting factors were administered by continuous infusion, 106 ± 13 UI/kg when SHL factors were administered by bolus infusion, and 75 ± 22 UI/kg when EHL factors were administered by bolus infusion. During hospitalisation, the mean factor cost was €38,073 (83.7% of the total cost of surgery). Mean blood loss was significantly lower in patients treated with tranexamic acid (164 mL, range: 40-300) than in those not (300 mL, range: 70-800; p = .01). Six patients had haematoma. The 10-year survival free of any prosthesis removal/arthrodesis was estimated to be 92.2% (95% CI [83; 100]). CONCLUSION: The medical therapeutic management of TAR is complex, carried out by a multidisciplinary team but effective in avoiding the occurrence of complications.

Comparison of one-stage and chromogenic factor VIII assays to tailor the dose of recombinant factor VIII-Fc fusion protein (rFVIIIFc, efmoroctocog alfa) in adult patients with haemophilia A: Single-centre, real-world experience of surgery.

BACKGROUND: Efmoroctocog alfa (rFVIIIFc) is an extended half-life FVIII used notably in surgery for patients with haemophilia A. More information is needed of its usage in real-life. METHODS: Adult patients with HA followed at the Lyon Comprehensive Hemophilia Care Center who underwent a surgery with rFVIIIFc were included in this retrospective analysis. The pharmacokinetics of rFVIIIFc was assessed by plasma factor VIII clotting activity (FVIII:C) using both one-stage (OSA) and chromogenic substrate (CSA) assays. RESULTS: A total of 39 major and 31 minor surgeries were performed in 49 patients treated with rFVIIIFc. The median dose of rFVIIIFc infused before major and minor surgeries respectively was 67.5 ((interquartile range [IQR] 52.6-76.9) and 48.0 (38.5-51.8) IU/kg. For major surgeries, during the first postoperative week, the median residual FVIII:C was 78 (64.5-101.5) IU/dL with OSA and 99 (71-118) IU/dL with CSA (p < .0001). After surgery, rFVIIIFc doses were adjusted according to CSA results. This led to a significant decrease of rFVIIIFc consumption compared to what would have been proposed according to the OSA assay, without unusual bleeding or appearance of inhibitor. Considering the high price of the molecule, this was also associated with a significant cost reduction. CONCLUSION: Dose adjustment of rFVIIIFc according to FVIII: C measured by CSA is effective, safe and well tolerated in patients with haemophilia A undergoing invasive surgery.

Evaluation of the care pathway in the context of the dispensing of emicizumab (Hemlibra) in community and hospital pharmacies in France: A patient satisfaction survey.

INTRODUCTION: Since June 2021 in France, patients with haemophilia A with anti-factor VIII inhibitors and patients with severe haemophilia A without anti-factor VIII inhibitors, and treated with emicizumab (Hemlibra), have to choose the dispensing circuit community or hospital pharmacy. AIM: To evaluate satisfaction of patients whether they choose dispensation from a community pharmacy or retained dispensation from the hospital pharmacy, to understand the main motivation for choosing the community or the hospital pharmacy. METHODS: All patients living in France, regardless of age, were eligible to participate. Between September 13, 2022, and January 9, 2023, 175 respondents answered the satisfaction survey, including 123 in community pharmacy and 52 in hospital pharmacy. RESULTS: Eighteen months after availability in community pharmacies, treatment accessibility is improved for the benefit of the patient. The door-to-door travel times are significantly reduced to the community pharmacy with an average gain of 16.5 min saved from the place of residence. Patients are mostly satisfied with the new dispensing circuit especially concerning the overall satisfaction (p < .0001), the travel time (p < .0001) and the strong relationship with the pharmacist (p = .0022) compared to hospital pharmacy. CONCLUSION: Innovation in care pathways is showing its full potential in improving access to medication, made possible by the implementation of a rigorous organization accompanied by training to enable healthcare professionals involved in primary care to provide appropriate management.

Evaluation of the Care Pathway in the Context of the Dispensing of Emicizumab (Hemlibra) in Community Pharmacies in France: Protocol for a Cross-sectional Study Based on the Kirkpatrick Model.

BACKGROUND: Commercialized since 2019, emicizumab (Hemlibra) was available only in French hospital pharmacies for prophylaxis of hemophilia A with or without inhibitors. Since June 15, 2021, patients can choose between a hospital and community pharmacy. These changes in the care pathway have important organizational consequences for patients, their relatives, and health professionals. Two training programs are available for community pharmacists: the "HEMOPHAR" training program proposed by the national reference center for hemophilia and the Roche training program proposed by the laboratory that markets the product. OBJECTIVE: The PASODOBLEDEMI study aims to evaluate the direct impact of the training programs provided to community pharmacists in the context of the dispensing of emicizumab, and to evaluate patients' satisfaction with their treatment whether they choose dispensation from a community pharmacy or retained dispensation from the hospital pharmacy. METHODS: We designed a cross-sectional study based on the 4-level Kirkpatrick evaluation model: the immediate reaction of community pharmacists following training (Reaction), the knowledge acquired during the training (Learning), the professional practice of community pharmacists during dispensing of the product (Behavior), and patients' satisfaction related to the treatment whether it is dispensed from a hospital or from a community pharmacy (Results). RESULTS: Considering that single outcome measures cannot adequately reflect the complexity of this new organization, the Kirkpatrick evaluation model provides 4 distinct outcomes: the immediate reaction after the HEMOPHAR training program, the level of knowledge acquired after the HEMOPHAR training program, the impact of training on professional practice, and patient satisfaction with access to emicizumab. We developed specialized questionnaires for each of the 4 levels of the Kirkpatrick evaluation model. All community pharmacists involved in dispensing emicizumab, whether they have followed the HEMOPHAR or the Roche training program or neither, were eligible for inclusion. All patients with severe hemophilia A were eligible, irrespective of inhibitor use, age, treatment with emicizumab, and whether they chose dispensation from a community pharmacy or retained dispensation from a hospital pharmacy. CONCLUSIONS: The new organization for dispensing emicizumab to patients with hemophilia A in French community pharmacies must be accompanied by optimal safety and quality conditions due to the risk of serious and urgent bleeding situations in the management of rare bleeding diseases. The elaboration of the PASODOBLEDEMI protocol has already a positive impact with the commitment of all health professionals, physicians, hospital and community pharmacists, and the patient community. The results will be disseminated among the French authorities and will enable, if necessary, proposing this access model to other rare diseases. TRIAL REGISTRATION: ClinicalTrials.gov NCT05449197, https://clinicaltrials.gov/ct2/show/NCT05449197?term=NCT05449197; ClinicalTrials.gov NCT05450640, https://clinicaltrials.gov/ct2/show/NCT05450640?term=NCT05450640. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/43091.

Management of rare inherited bleeding disorders: Proposals of the French Reference Centre on Haemophilia and Rare Coagulation Disorders.

INTRODUCTION: The rare coagulation disorders may present significant difficulties in diagnosis and management. In addition, considerable inter-individual variation in bleeding phenotype is observed amongst affected individuals, making the bleeding risk difficult to assess in affected individuals. The last international recommendations on rare inherited bleeding disorders (RIBDs) were published by the United Kingdom Haemophilia Centre Doctors' Organisation in 2014. Since then, new drugs have been marketed, news studies on surgery management in patients with RIBD have been published, and new orphan diseases have been described. AIM: Therefore, the two main objectives of this review, based on the recent recommendations published by the French Reference Centre on Haemophilia and Rare Bleeding Disorders, are: (i) to briefly describe RIBD (clinical presentation and diagnostic work-up) to help physicians in patient screening for the early detection of such disorders; and (ii) to focus on the current management of acute haemorrhages and long term prophylaxis, surgical interventions, and pregnancy/delivery in patients with RIBD.

Rituximab as induction therapy in pediatric kidney transplantation: A single-center experience in four patients.

BACKGROUND: The anti-CD20 rituximab is often used in the treatment of children with steroid-resistant nephrotic syndrome or EBV-induced post-transplant lymphoproliferative disorder. This single-center series reports the use of rituximab as induction therapy in pediatric kidney transplantation. METHODS: Four children who received rituximab as induction therapy for kidney transplantation since 2016 were retrospectively analyzed. Clinical and laboratory data were extracted from medical records. RESULTS: The patients (2 boys and 2 girls) were aged from 6.1 to 11.9 years and were treated with rituximab on the day of the transplantation procedure; all the transplants came from deceased donors. In all patients, rituximab was used because of positive EBV viral loads before kidney transplantation. Viral loads remained undetectable for the first 6 months after the transplantation procedure and remained below the 4.5 log threshold thereafter. After a median follow-up of 2.3 years, none of the patients displayed rejection or de novo donor-specific antibodies; the glomerular filtration rate remained above 70 ml/min/1.73 m2 . No post-transplant lymphoproliferative disorder was observed. CONCLUSION: The results suggest that rituximab can be used as induction therapy to prevent EBV replication and its complications in case of positive viral load prior to kidney transplantation.

Polypharmacy and medication regimen complexity in older patients with hemophilia or von willebrand disease: the M'HEMORRH-AGE study.

BACKGROUND: In older patients, multiple chronic conditions lead topolypharmacy which is associated with a higher risk of adverse drug events. Nowadays, the medication exposure of older patients with bleeding disorders has been poorly explored. AIM: The aim of this study was to assess the prevalence of polypharmacy and the medication regimen complexity in older community-dwelling patients with hemophilia or von Willebrand Disease (VWD). METHOD: The M'HEMORRH-AGE study (Medication in AGEd patients with HEMORRHagic disease) is a multicenter prospective observational study. Community-dwelling patients over 65 years with hemophilia or VWD were included in the study. The rate of polypharmacy (use of 5 to 9 drugs daily) and excessive polypharmacy (use of 10 or more medications daily) was assessed. The complexity of prescribed medication regimens was assessed using the Medication Regimen Complexity Index (MRCI). RESULTS: Overall, 142 older community-dwelling patients with hemophilia (n = 89) or VWD (n = 53) were included (mean age: 72.8 (5.8) years). Prevalence of polypharmacy and excessive polypharmacy were 40.8% and 17.6%, respectively. The mean MRCI score was 16.9 (6.1). The mean MRCI score related to bleeding disorders medications was 6.9 (1.1). There was no significant difference between older hemophilia patients and VWD patients. CONCLUSION: The M'HEMORRH-AGE study showed that more than half of older community-dwelling patients were affected by polypharmacy. In addition, the high medication regimen complexity in this older population suggests that interventions focusing on medication review and deprescribing should be conducted to reduce polypharmacy with its negative health-related outcomes.

Continuous Infusion of Factor VIII and von Willebrand Factor in Surgery: Trials with pdFVIII LFB or pdVWF LFB in Patients with Bleeding Disorders.

BACKGROUND: A plasma-derived factor VIII product (pdFVIII; Factane 100 or 200 IU/mL) and a plasma-derived von Willebrand factor product (pdVWF; Wilfactin 100 IU/mL) are approved for replacement therapy by intravenous bolus injections in hemophilia A (HA) and von Willebrand disease (VWD), respectively. However, in situations requiring intensive treatment, continuous infusion (CI) may be desirable to better control target plasma factor levels. AIM: To evaluate the perioperative hemostatic efficacy and safety of these concentrates administered by CI. METHODS: Three phase III trials were conducted. Adults with HA (FVIII:C < 1%) (studies 1 and 2) or VWD (VWF:RCo < 20%) (Study 3) received a preoperative bolus followed by CI of undiluted concentrate for at least 6 days. Bolus doses and CI rates were based on individual recovery and clearance, respectively. The initial infusion rate had to be higher for 48 hours for HA and 24 hours for VWD patients to anticipate potential fluctuations of factor concentrations during major surgery. Target levels of FVIII:C in HA and VWF:RCo in VWD were 80 and 70 IU/dL, respectively. Efficacy was assessed using a global hemostatic efficacy score. RESULTS: Studies 1, 2, and 3 included 12, 4, and 6 patients, respectively. Efficacy outcomes were excellent/good in all 22 major surgeries including 18 orthopedic procedures. Most daily measured FVIII and VWF levels (92%) were on target. No safety concerns, thrombotic events, or inhibitors were identified. CONCLUSION: pdFVIII and pdVWF administered by CI represent an effective and safe alternative to bolus injections in patients with severe HA or VWD undergoing surgery.

PHAREO study: Perceived and observed accessibility to therapeutic drugs used for treating patients with inherited bleeding disorders.

WHAT IS KNOWN AND OBJECTIVE: The dispensing of clotting factor concentrates in hospital pharmacies imposes accessibility constraints on patients and their caregivers, thereby increasing the disease burden. Very few studies have addressed these issues so far in terms of individual perceptions and actual difficulties. The PHAREO study aims to report patient's perception of treatment accessibility and evaluate spatial accessibility. METHODS: The PHAREO study is an observational survey based on a questionnaire specifically designed for the study purpose in collaboration with patients' representatives in the second demographic and economic French region. RESULTS AND DISCUSSION: We collected 293 responses (participation rate of 64.1%) which show that 89.8% of respondents were either very or rather satisfied with regard to access to treatment. However, respondents reported difficulties in accessing the hospital pharmacy. The data also showed that 79.2% of respondents tended to over-estimate travel time which was reported above their acceptable threshold for 39.2% of them. The main determinants of dissatisfaction were parental burden (OR 2.5 [1.3; 4.8], p = 0.008) and waiting time at the hospital pharmacy (OR 1.5 [1.1;2.0], p = 0.016, per 10 min increase). WHAT IS NEW AND CONCLUSION: The PHAREO study provides subjective and objective data regarding satisfaction levels of persons with haemophilia and other coagulation deficiencies, with a high representativeness rate for patients on prophylaxis (87.5%). Both respondents and hospital pharmacists pled for an evolution of the current dispensing circuit to improve access to treatment and reduce the burden for patients. Currently, the community pharmacists are apart from the dispensing circuit. The authors propose improvements in the pathway of care for patients and their caregivers by including the community pharmacists alongside the hospital pharmacists in a centralized coordination scheme.

Potentially inappropriate medications and anticholinergic and sedative burden in older patients with haemophilia or von Willebrand disease: The M'HEMORRH-AGE study.

WHAT IS KNOWN AND OBJECTIVE: In older patients, multiple chronic conditions lead to the intake of multiple medications and a higher risk of adverse drug events. The exposure to inappropriate medications in older patients with bleeding disorders is poorly explored. The aim of this study was to describe the exposure to potentially inappropriate medications (PIMs) and medications with anticholinergic and sedative properties in older community-dwelling patients with haemophilia or von Willebrand Disease (VWD). METHODS: The M'HEMORRH-AGE study (Medication in AGEd patients with HAEMORRHagic disease) is a multicentre prospective observational study. Community-dwelling patients over 65 years with haemophilia or VWD were included in the study. PIMs were identified using the EU(7)-PIM list, and the anticholinergic and sedative drug exposure was measured using the Drug Burden Index. RESULTS AND DISCUSSION: 142 older community-dwelling patients with haemophilia (n = 89) or VWD (n = 53) were included (mean age: 72.8 ± 5.8 years). PIMs were used by 45.8% of older patients and were mainly represented by cardiovascular (34.9%), nervous systems (26.7%) and alimentary tract and metabolism PIMs (25.6%). Regarding anticholinergic and/or sedative medications, 37.3% of older patients were exposed mainly due to nervous system medications (68.3%), for example analgesics. WHAT IS NEW AND CONCLUSION: The M'HEMORRH-AGE study showed the exposure to PIMs and anticholinergic/sedative medications was high in older community-dwelling patients with haemophilia or VWD. Interventions focusing on deprescription of these inappropriate medications should be conducted in this specific population.

Patients' Perception of the Impact of Innovation on Hemophilia Care Management Organization: A Qualitative Study Protocol (INNOVHEMO Study).

BACKGROUND: New therapies provide a favorable evolution in the care management of persons with hemophilia. However, the impact of these new therapies on patient care organization remains to be determined. A qualitative study will be implemented to analyze patients' perception regarding the impact of innovation on the organization of their care management. Secondary objectives will include refining specific factors related to persons with hemophilia (barriers or facilitators, especially the place of treatment) to consider within an organizational impact analysis. PATIENTS AND METHODS: Semi-structured individual interviews will be conducted via videoconferencing or by phone by two researchers using an interview guide. Participants will be recruited from the Rhône-Alpes region, in France. Physicians from two hemophilia treatment centers will identify eligible patients. Moreover, a call for volunteers will be launched by the Rhône-Alpes committee of the French hemophilia association. Interviews will be conducted with adult patients, adolescent patients or parents of a minor with hemophilia regularly treated prophylactically or on demand. Data analysis will be performed with NVivo® software. Each interview will be analyzed by two researchers using an inductive content analytic method. DISCUSSION: The INNOVHEMO study is an original study analyzing the way patients perceive the impact of an innovation on their care management organization. The resulting patient-specific factors, identified as barriers or facilitators, will need to be integrated into a more comprehensive analysis of the impact of innovation on care management organization.

Haemophilia A patients' medication adherence to prophylaxis with efmoroctocog alfa.

INTRODUCTION: Lightening the injection burden is commonly believed to improve prophylaxis adherence. Efmoroctocog alfa (rFVIIIFc) is the first recombinant FVIII-Fc fusion protein available in France. This clotting factor with an extended half-life could thus improve medication adherence. AIM: The study primarily aimed to assess the real-life impact on prophylaxis adherence of haemophilia A patients, when switching from a standard to an extended half-life FVIII. METHODS: This study was an observational, monocentre, non-interventional study aiming at assessing haemophilia A patients' real-life adherence during the first-year post-rFVIIIFc prophylaxis initiation. Medication adherence was assessed using two methods: the medication possession ratio (MPR), which is based on the hospital pharmacy dispensing data, and self-reported VERITAS-Pro® questionnaire. Patients on rFVIIIFc prophylaxis for at least 12 months, following a 12-month standard FVIII prophylaxis, were eligible for inclusion. RESULTS: In 2019, 47 male patients were undergoing rFVIIIFc prophylaxis in our Hemophilia Center, among which 36 meeting the inclusion criteria. Switching from standard to extended half-life FVIII prophylaxis resulted in increased mean dosing, while the mean number of weekly prophylactic injections (2.6 ± 0.5 vs 1.8 ± 0.3) decreased. Following rFVIIIFc initiation, a non-significant increase in median MPR occurred and the self-reported VERITAS-Pro® questionnaire demonstrated improved adherence to rFVIIIFc prophylaxis. Comparing adherent and non-adherent patients revealed age as the only factor likely to impact adherence (p = .07). CONCLUSION: Our patient cohort exhibited high adherence levels before and after FVIII switching, based on MPR and VERITAS-Pro® questionnaire. The latter is likely a useful tool to quantity prophylaxis adherence from a patient's perspective in daily use.

Evolution of clotting factor concentrates prescriptions and impact of recommendations of prophylaxis in children with haemophilia.

Prophylaxis treatment is considered as the reference approach for children with severe haemophilia A or B. However, no consensus about the best prophylaxis protocol has yet been identified in term of dosage and timing of infusions. Guidelines were drawn up in France in the early 2000s by an expert group. The objective of this 16-year study (2001 to 2016) was to describe the clotting factor concentrates (CFCs) use in haemophiac outpatients. This is a retrospective monocentric study. Pharmaceutical and clinical data were captured using medical records. Main outcome measures are CFCs use and clinical data in paediatrics. Eighty haemophiliacs A or B under 12 years old with a factor level less than 2% were included (74% of HA), from pharmaceutical outpatient data. Global use of CFCs followed the evolution of the patients' number and regimen type introduced: increase of prophylaxis and decrease of on demand regimen. The average age at the prophylaxis introduction is significantly different according to the birth year. Prophylaxis introduction was made earlier with an increase of prophylactic regimen joined to an increase of CFCs use. The significant reduction of haemarthrosis in our cohort can be linked to a first infusion age and a prophylaxis introduction much earlier.

A novel protocol for accurate and reliable postoperative bolus administration of recombinant factor VIIa using an automated mini-pump system.

INTRODUCTION: Recombinant FVIIa (rFVIIa) is widely used to manage bleeding risk during and after surgery in patients with haemophilia complicated by inhibitors. In the postoperative period, rFVIIa must be delivered frequently and regularly to maintain haemostasis, considering its short half-life. Preparation and manual administration of bolus doses of rFVIIa at regular intervals may place a strain on available nursing resources. A programmable mini-pump may offer an approach to facilitate regular administration of bolus doses of rFVIIa at specified intervals. AIM: To investigate if a mini-pump is a practical and effective way to deliver rFVIIa in the postoperative period. METHODS: It was first necessary to establish that rFVIIa remains stable and sterile in the mini-pump reservoir for an extended period. Four days after loading the mini-pump under sterile conditions no evidence of bacterial or fungal growth was observed and in vitro procoagulant activity of rFVIIa remained stable. The mini-pump was used to deliver rFVIIa as bolus doses to two patients with inhibitors who had undergone surgery. Nurses were asked to report their satisfaction with the use of the mini-pump using a specific questionnaire. RESULTS: Haemostasis was evaluated as excellent in both cases; nurses were satisfied with use of the mini-pump. CONCLUSION: This pilot study shows that intermittent delivery of rFVIIa at fixed intervals using an automated mini-pump offers accurate and reliable administration in the postoperative setting. This approach may reduce burden on nursing staff, potentially minimize the risk of human error and avoid delay in administration of rFVIIa.

Access to treatment among persons with hemophilia: A spatial analysis assessment in the Rhone-Alpes region, France.

OBJECTIVES: In France, only hospital pharmacies can dispense clotting factor concentrates to persons with hemophilia, which limits the access to care for the treatment and the prevention of bleeding episodes. Moreover, the cost of clotting factor concentrates may restrain the maintenance of sufficient stocks in hospital pharmacies. The aim of this study was to investigate the accessibility of clotting factor concentrates to persons with hemophilia in the context of long-term prophylaxis and emergency treatment in the Rhone-Alpes region of France. METHODS: A geographic information system was used for evaluating accessibility of clotting factor concentrates. Persons with hemophilia and hospital pharmacies were geolocalized with the use of postal data, and the evaluation of accessibility was based on the road network. RESULTS: Approximately 72% of the study area was accessible in less than 30 minutes to a hospital pharmacy. Eighty-five percent of persons with hemophilia had access to clotting factor concentrates for prophylactic treatment in less than 20 minutes. Most of them were patients with severe or moderate hemophilia. Regarding emergency doses, factor VIII was accessible in less than 30 minutes in 45.6% of the study area, and factor IX in 30.5%. CONCLUSION: This study highlights that spatial access to clotting factor concentrates by persons with hemophilia in the Rhône-Alpes region is good for prophylactic treatment but is more uneven for emergency doses.

Management of bleeding and invasive procedures in haemophilia A patients with inhibitor treated with emicizumab (Hemlibra® ): Proposals from the French network on inherited bleeding disorders (MHEMO), the French Reference Centre on Haemophilia, in collaboration with the French Working Group on Perioperative Haemostasis (GIHP).

INTRODUCTION: Emicizumab (Hemlibra® ) recently became available and requires an adaptation for managing bleeding, suspected bleeding and emergency or scheduled invasive procedures in haemophilia A patients with inhibitor. This implicates a multidisciplinary approach and redaction of recommendations for care that must be regularly adapted to the available data. AIM: The following text aims to provide a guide for the management of people with haemophilia A with inhibitor treated with emicizumab in case of bleeding or invasives procedures. METHODS: The French network on inherited bleeding disorders (MHEMO), the French Reference Centre on Haemophilia (CRH), in collaboration with the French Working Group on Perioperative Haemostasis (GIHP) have been working together to make proposals for the management of these situations. RESULTS: Haemostatic treatment and other medications should be given stepwise, according to the severity and location of the bleeding or the risk of bleeding of the procedure as well as the haemostatic response obtained at each step in order to ensure an optimal benefit/risk ratio. CONCLUSION: The lack of data means that it is only possible to issue proposals rather than recommendations.