| 1. |
- Astermark, Jan, et al.
(author)
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Considerations for shared decision management in previously untreated patients with hemophilia A or B
- 2023
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In: Therapeutic advances in hematology. - 2040-6207. ; 14
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Research review (peer-reviewed)abstract
- 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 professionals are tasked with helping children achieve an inclusive quality of life and maintain good joint health into adulthood. Primary prophylaxis is the gold standard to optimize outcomes and is recommended to start before 2 years of age. A range of topics need to be discussed with parents to aid their understanding of the decisions they can make and how these will affect the management of their child/children. For those with a family history of hemophilia, prenatal considerations include the possibility of genetic counseling, prenatal investigations, and planning for delivery, together with monitoring of the mother and neonate, as well as diagnosis of the newborn and treatment of any birth-associated bleeding. Subsequent considerations, which are also applicable to families where infant bleeding has resulted in a new diagnosis of sporadic hemophilia, involve explaining bleed recognition and treatment options, practical aspects of initiating/continuing prophylaxis, dealing with bleeds, and ongoing aspects of treatment, including possible inhibitor development. Over time, optimizing treatment efficacy, in which individualizing therapy around activities can play a role, and long-term considerations, including retaining joint health and tolerance maintenance, become increasingly important. The evolving treatment landscape is creating a need for continually updated guidance. Multidisciplinary teams and peers from patient organizations can help provide relevant information. Easily accessible, multidisciplinary comprehensive care remains a foundation to care. Equipping parents early with the knowledge to facilitate truly informed decision-making will help achieve the best possible longer-term health equity and quality of life for the child and family living with hemophilia. Plain language summary: Points to be taken into account to help families make decisions to best care for children born with hemophilia Medical advances are providing a range of treatment options for adults and children with hemophilia. There is, however, relatively limited information about managing newborns with the condition. Doctors and nurses can help parents to understand the choices for infants born with hemophilia. We describe the various points doctors and nurses should ideally discuss with families to enable informed decision-making. We focus on infants who require early treatment to prevent spontaneous or traumatic bleeding (prophylaxis), which is recommended to start before 2 years of age. Families with a history of hemophilia may benefit from discussions before pregnancy, including how an affected child would be treated to protect against bleeds. When mothers are pregnant, doctors can explain investigations that can provide information about their unborn child, plan for the birth, and monitor mother and baby to minimize bleed risks at delivery. Testing will confirm whether the baby is affected by hemophilia. Not all infants with hemophilia will be born to families with a history of the condition. Identification of hemophilia for the first time in a family (which is ‘sporadic hemophilia’) occurs in previously undiagnosed infants who have bleeds requiring medical advice and possibly hospital treatment. Before any mothers and babies with hemophilia are discharged from hospital, doctors and nurses will explain to parents how to recognize bleeding and available treatment options can be discussed. Over time, ongoing discussions will help parents to make informed treatment decisions: • When and how to start, then continue, prophylaxis. • How to deal with bleeds (reinforcing previous discussions about bleed recognition and treatment) and other ongoing aspects of treatment. ○ For instance, children may develop neutralizing antibodies (inhibitors) to treatment they are receiving, requiring a change to the planned approach. • Ensuring treatment remains effective as their child grows, considering the varied needs and activities of their child.
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| 2. |
- Astermark, Jan, et al.
(author)
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New Inhibitors in the Ageing Population : A Retrospective, Observational, Cohort Study of New Inhibitors in Older People with Hemophilia
- 2022
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In: Thrombosis and Haemostasis. - : Georg Thieme Verlag KG. - 0340-6245 .- 2567-689X. ; 122:6, s. 905-912
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Journal article (peer-reviewed)abstract
- Introduction A second peak of inhibitors has been reported in patients with severe hemophilia A (HA) aged >50 years in the United Kingdom. The reason for this suggested breakdown of tolerance in the aging population is unclear, as is the potential impact of regular exposure to the deficient factor by prophylaxis at higher age. No data on hemophilia B (HB) have ever been reported. Aim The ADVANCE Working Group investigated the incidence of late-onset inhibitors and the use of prophylaxis in patients with HA and HB aged ≥40 years. Methods A retrospective, observational, cohort, survey-based study of all patients aged ≥40 years with HA or HB treated at an ADVANCE hemophilia treatment center. Results Information on 3,095 people aged ≥40 years with HA or HB was collected. Of the 2,562 patients with severe HA, the majority (73% across all age groups) received prophylaxis. In patients with severe HA, the inhibitor incidence per 1,000 treatment years was 2.37 (age 40-49), 1.25 (age 50-59), and 1.45 (age 60 +). Overall, the inhibitor incidence was greatest in those with moderate HA (5.77 [age 40-49], 6.59 [age 50-59], and 4.69 [age 60 + ]) and the majority of inhibitor cases were preceded by a potential immune system challenge. No inhibitors in patients with HB were reported. Conclusion Our data do not identify a second peak of inhibitor development in older patients with hemophilia. Prophylaxis may be beneficial in older patients with severe, and possibly moderate HA, to retain a tolerant state at a higher age.
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| 3. |
- Astermark, Jan, et al.
(author)
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Recombinant factor IX Fc prophylaxis reduces pain and increases levels of physical activity, with sustained, long-term improvements in patients with hemophilia B : post hoc analysis of phase III trials using patient-reported outcomes
- 2023
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In: Therapeutic advances in hematology. - 2040-6207. ; 14
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Journal article (peer-reviewed)abstract
- Background: Pain is a common symptom of hemophilia that may adversely affect patients’ quality of life (QoL). Previous post hoc analyses of prophylaxis with recombinant factor IX Fc fusion protein (rFIXFc) have been published for adults and adolescents, demonstrating improvements in health-related QoL (HRQoL) when assessed by the haemophilia-specific QoL (HaemAQoL) questionnaire. Objective: To describe in depth the evolution of QoL, pain- and activity-related domains and questions for pediatric, adolescent, and adult patients with hemophilia B treated with rFIXFc prophylaxis. Design: A post hoc analysis of data from a series of clinical trials. Methods: This post hoc, long-term analysis assessed patient-reported outcomes (PROs) from the Kids B-LONG (NCT01440946: pediatric) and B-LONG (NCT01027364: adults and adolescents) parent studies and the B-YOND (NCT01425723: all age groups) extension study. Results: Ninety-two adult and adolescent patients that started in the B-LONG study were assessed, with a median (range) duration of follow-up of 58.9 (0.0–78.4) months. The Haem-A-QoL total score was significantly reduced from baseline by 4.45 (p ⩽ 0.01), as were the subdomains ‘physical health’ (9.10; p = 0.001), ‘sports and leisure’ (11.25; p ⩽ 0.01), ‘treatment’ (2.69; p = 0.05), and ‘view of self’ (5.81; p = 0.002). Thirty pediatric patients that started in the Kids B-LONG study were assessed, with a median (min–max) duration of follow-up of 36.7 (9.0–59.9) months. The high level of satisfaction demonstrated by the PROs at baseline was maintained. Conclusion: rFIXFc prophylaxis reduced perceived pain and increased levels of physical activity with sustained, long-term improvements in QoL in adult and adolescent patients with hemophilia B and maintained high QoL scores in pediatric patients.
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| 4. |
- Astermark, Jan, et al.
(author)
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rFIXFc prophylaxis improves pain and levels of physical activity in haemophilia B : Post hoc analysis of B-LONG using haemophilia-specific quality of life questionnaires
- 2022
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In: Haemophilia. - : Wiley. - 1351-8216 .- 1365-2516. ; 28:1, s. 18-26
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Journal article (peer-reviewed)abstract
- Introduction: Recurrent bleeding in severe haemophilia B causes painful hemarthroses and reduces capacity for physical activity. Recombinant factor IX Fc fusion protein (rFIXFc) prophylaxis results in low annualised bleeding rates, with the potential to improve patients’ health-related quality of life (HRQoL). Aim: To present a post hoc analysis of data from B-LONG describing change over time in patient-reported outcomes associated with pain and physical activity. Methods: Patients (≥12 years) who received weekly dose-adjusted or interval-adjusted rFIXFc prophylaxis and completed the Haemophilia-Specific QoL questionnaire for adolescents (Haemo-QoL) or adults (Haem-A-QoL) at baseline (BL) and end of study (EoS). Individual level changes in items of the ‘Physical Health’ and ‘Sports and Leisure’ domains, categorised as ‘never/rarely/seldom’ or ‘sometimes/often/all the time’, were analysed using McNemar's test to compare distribution of responses at EoS versus BL. Results: At EoS versus BL, a significantly greater proportion of patients did not experience painful swellings (64% vs. 44%; P =.004), painful joints (44% vs. 28%; P =.003) or pain when moving (54% vs. 41%; P =.026). Additionally, at EoS versus BL, patients were less likely to avoid participating in sports like football (30% vs. 8%; P =.002), avoid sports due to their haemophilia (47% vs. 27%; P =.007), or experience difficulty walking as far as they wanted (63% vs. 43%; P =.001). The proportion of patients who played sports as much as the general population was numerically increased (52% vs. 37%; P =.033) at EoS versus BL. Conclusion: Results of the analysis suggest that over time, rFIXFc prophylaxis is associated with significant improvements in pain and physical functioning. This contributes to previous evidence of overall HRQoL improvements in patients with haemophilia B treated with rFIXFc.
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| 5. |
- Auerswald, Günter, et al.
(author)
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Pain and pain management in haemophilia
- 2016
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In: Blood Coagulation and Fibrinolysis. - 0957-5235. ; 27:8, s. 845-854
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Research review (peer-reviewed)abstract
- Joint pain is common in haemophilia and may be acute or chronic. Effective pain management in haemophilia is essential to reduce the burden that pain imposes on patients. However, the choice of appropriate pain-relieving measures is challenging, as there is a complex interplay of factors affecting pain perception. This can manifest as differences in patients’ experiences and response to pain, which require an individualized approach to pain management. Prophylaxis with factor replacement reduces the likelihood of bleeds and bleed-related pain, whereas on-demand therapy ensures rapid bleed resolution and pain relief. Although use of replacement or bypassing therapy is often the first intervention for pain, additional pain relief strategies may be required. There is an array of analgesic options, but consideration should be paid to the adverse effects of each class. Nevertheless, a combination of medications that act at different points in the pain pathway may be beneficial. Nonpharmacological measures may also help patients and include active coping strategies; rest, ice, compression, and elevation; complementary therapies; and physiotherapy. Joint aspiration may also reduce acute joint pain, and joint steroid injections may alleviate chronic pain. In the longer term, increasing use of prophylaxis or performing surgery may be necessary to reduce the burden of pain caused by the degenerative effects of repeated bleeds. Whichever treatment option is chosen, it is important to monitor pain and adjust patient management accordingly. Beyond specific pain management approaches, ongoing collaboration between multidisciplinary teams, which should include physiotherapists and pain specialists, may improve outcomes for patients.This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License, where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially. http://creativecommons.org/licenses/by-nc-nd/4.0
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| 6. |
- Benson, Gary, et al.
(author)
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Diagnosis and care of patients with mild haemophilia : practical recommendations for clinical management
- 2018
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In: Blood Transfusion. - 1723-2007. ; , s. 535-544
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Research review (peer-reviewed)abstract
- Mild haemophilia is defined by factor levels between 0.05 and 0.40 IU/mL and is characterised by traumatic bleeds. Major issues associated with mild haemophilia are that it may not present for many years after birth, and that awareness, even within families, may be low. Methodological problems exist in diagnosis, such as inconsistencies in results obtained from different assays used to measure factor levels in mild haemophilia. Advances in genetic testing provide insight into diagnosis as well as the likelihood of inhibitor development, which is not uncommon in patients with mild or moderate haemophilia and can increase morbidity. The management of patients with mild haemophilia is a challenge. This review includes suggestions around formulating treatment plans for these patients, encompassing the full spectrum from clinical care of the newly diagnosed neonate to that of the ageing patient with multiple comorbidities. Management strategies consider not only the vast differences in these patients' needs, but also risks of inhibitor development and approaches to optimally engage patients.
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| 7. |
- Berntorp, Erik, et al.
(author)
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Optimising prophylaxis in haemophilia A : The ups and downs of treatment
- 2021
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In: Blood Reviews. - : Elsevier BV. - 0268-960X. ; 50
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Research review (peer-reviewed)abstract
- 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, and may change for the same individual over time, meaning that a standardised dose and regimen may not provide optimal protection to all patients. Here we review the evolving treatment landscape for haemophilia A, and discuss how an increased understanding of the pharmacology and pharmacokinetics underlying FVIII replacement and non-factor replacement therapies could improve patient outcomes. We also review the strengths and weaknesses of current treatments and explore the benefits of personalised therapy and review how this may best be achieved with current treatment options. The key points of our review are summarised in this accompanying short video.
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| 8. |
- Dolan, Gerry, et al.
(author)
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Haemophilia B : Where are we now and what does the future hold?
- 2018
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In: Blood Reviews. - : Elsevier BV. - 0268-960X. ; 32:1, s. 52-60
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Research review (peer-reviewed)abstract
- Research has been lacking on the natural history, complications, and treatment of haemophilia B, which is less common than haemophilia A and was recognized as a distinct clinical entity in 1947. Although the two diseases share the same clinical manifestations, they differ in causative mutation, risk of inhibitor development, and patient quality of life. Frequently debated is whether haemophilia B is as clinically severe as haemophilia A, with much of the published data on overall and haemophilia-specific health outcomes suggesting that haemophilia B may have a less severe clinical phenotype. However, although fewer haemophilia B than haemophilia A patients appear to experience bleeding, bleeds are just as severe. We review distinguishing characteristics of haemophilia B and its treatment, including management strategies for neonates, therapeutic approaches for patients who develop inhibitors, pharmacokinetics of factor IX concentrates administered as replacement therapy, and potential future treatments.
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| 9. |
- Dolan, Gerry, et al.
(author)
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Principles of Care for Acquired Hemophilia
- 2021
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In: European Journal of Haematology. - : Wiley. - 1600-0609 .- 0902-4441. ; 106:6, s. 762-773
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Journal article (peer-reviewed)abstract
- 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 specialists.RESULTS: The 10 proposed principles for AHA care are as follows: 1) Improving initial diagnosis of AHA; 2) Differential diagnosis of AHA: laboratory assessment of patients with unusual bleeding; 3) Effective communication between laboratories, physicians, and specialists; 4) Improving clinical care: networking between healthcare professionals in the treating hospital and specialist hemophilia centers; 5) Comprehensive assessment of bleeding; 6) Appropriate use of bypassing agents; 7) Long-term follow-up and monitoring for efficacy and safety of immunosuppressive treatment; 8) Inpatient/outpatient settings; 9) Access to innovative and disruptive treatments; 10) Promotion of international collaborative research.CONCLUSION: The proposed principles for holistic AHA care aim to ensure swift diagnosis and optimal patient management. Key to achieving this goal is training for healthcare personnel in non-specialist hospitals and collaboration between different specialists. We hope these principles will increase awareness of AHA in the wider medical community and catalyze efforts towards improving its practical, multidisciplinary management.
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| 10. |
- Dolan, Gerard, et al.
(author)
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Recombinant FVIIa in elective non-orthopaedic surgery of adults with haemophilia and inhibitors : A systematic literature review
- 2021
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In: Haemophilia. - : Wiley. - 1351-8216 .- 1365-2516. ; 27:3, s. 314-330
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Research review (peer-reviewed)abstract
- Aim: To assess available evidence on the use of rFVIIa in non-orthopaedic surgery including dental surgery in adult patients with congenital haemophilia with inhibitors (PWHI). Methods: A systematic literature search was performed according to a prespecified search string; prespecified criteria were used to select applicable studies including PWHI ≥18 years of age who underwent any non-orthopaedic surgery using rFVIIa. Results: Thirty-three publications met the eligibility criteria, of which 26 publications – including 46 procedures in 44 patients – were selected for the qualitative analysis. Most publications were case reports or case series (21/26). Primary authors assessed rFVIIa as effective in maintaining haemostasis during and after most major surgeries (22/32). rFVIIa dose was mainly on label, with higher doses used in 4 cases, and a lower dose in 1 case. Duration of treatment was mostly 5–10 days (range: 3 days to 1 month post-operatively). Adverse events related to rFVIIa were rare. Conclusions: Assessing non-orthopaedic surgery in this patient population is hampered by a paucity of published data; nevertheless, the current evidence indicates that rFVIIa is effective in achieving haemostasis in haemophilia patients with inhibitors undergoing elective non-orthopaedic or dental surgery. rFVIIa was generally well tolerated in these patients, with thrombotic events occurring rarely. These data, generated to help clinicians manage congenital haemophilia with inhibitors, highlight the need for more systematic reporting of rFVIIa and all other therapeutic agents in non-orthopaedic surgery and dental surgery in patients with congenital haemophilia and inhibitors.
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