| 1. |
- Auerswald, Günter, et al.
(författare)
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Pain and pain management in haemophilia
- 2016
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Ingår i: Blood Coagulation and Fibrinolysis. - 0957-5235. ; 27:8, s. 845-854
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Forskningsöversikt (refereegranskat)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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| 2. |
- Benson, Gary, et al.
(författare)
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Diagnosis and care of patients with mild haemophilia : practical recommendations for clinical management
- 2018
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Ingår i: Blood Transfusion. - 1723-2007. ; , s. 535-544
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Forskningsöversikt (refereegranskat)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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| 3. |
- Dolan, Gerry, et al.
(författare)
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Haemophilia B : Where are we now and what does the future hold?
- 2018
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Ingår i: Blood Reviews. - : Elsevier BV. - 0268-960X. ; 32:1, s. 52-60
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Forskningsöversikt (refereegranskat)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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| 4. |
- Dolan, Gerry, et al.
(författare)
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Principles of Care for Acquired Hemophilia
- 2021
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Ingår i: European Journal of Haematology. - : Wiley. - 1600-0609 .- 0902-4441. ; 106:6, s. 762-773
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Tidskriftsartikel (refereegranskat)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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| 5. |
- Hermans, Cedric, et al.
(författare)
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Outcome measures for adult and pediatric hemophilia patients with inhibitors
- 2017
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Ingår i: European Journal of Haematology. - : Wiley. - 0902-4441. ; 99:2, s. 103-111
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Forskningsöversikt (refereegranskat)abstract
- Recent advancements in almost all aspects of hemophilia treatment have vastly improved patient care and management, and new and emerging treatments hold the promise of further progress. However, there remains a scarcity of data on long-term outcomes in hemophilia, particularly among those patients with inhibitors, for whom no validated outcome assessment tools are currently available. At the 15th Zürich Haemophilia Forum, an expert panel reviewed the most important outcome measures in inhibitor patients and considered the challenges associated with assessing outcomes in this population. A framework for outcome assessment in inhibitor patients incorporates traditional hemophilia outcome measures, such as bleed frequency and mortality, alongside measures of health, functioning, disability, social participation, quality of life, and economic considerations. It is important to remember that inhibitor patients differ in their clinical needs, perspectives, and priorities according to age, inhibitor status, degree of joint disease, and activity levels; as a result, the relative importance of different outcome measures will change throughout an inhibitor patient's life. Challenges inherent in measuring long-term outcomes in inhibitor patients include the small number of known patients, the subjective nature of many outcome assessment tools, and the risk of overburdening patients with repeated requests to complete questionnaires or participate in studies. Therefore, there is an urgent need to reach consensus on the most important and appropriate assessment tools for measuring outcomes in this population. These tools should ideally be standardized, easily applied, and internationally applicable in order to collect and generate quality outcome data.
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| 6. |
- Jiménez-Yuste, Victor, et al.
(författare)
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Practical considerations for nonfactor-replacement therapies in the treatment of haemophilia with inhibitors
- 2021
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Ingår i: Haemophilia. - : Wiley. - 1351-8216 .- 1365-2516. ; 27:3, s. 340-350
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Forskningsöversikt (refereegranskat)abstract
- 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), and inhibition of anticoagulant proteins such as tissue factor pathway inhibitor (eg PF-06741086) and antithrombin (eg fitusiran). These agents are administered subcutaneously and should significantly reduce treatment burden and increase the ability to deliver prophylaxis for patients. Limited real-world data and validated practical guidance on these recently licensed/upcoming treatments resulted in the authors convening to discuss recommendations on their use. Emicizumab is currently the only licenced nonfactor therapy; thus, our recommendations focus on this product. Target candidates for emicizumab prophylaxis are difficult-to-treat patients with haemophilia A and inhibitors and/or venous access issues, frequent bleeds and target joints. In case of breakthrough bleeding while receiving emicizumab, patients still require treatment with bypassing agents; the adjunct treatment of choice is recombinant activated factor VII. This treatment is also recommended to prevent bleeds in patients with inhibitors undergoing surgery. Our recommendations on suitable laboratory assays and monitoring new products, as well as the benefit of patient-reported outcomes (such as pain and physical activity levels), are included. We also briefly discuss future treatment options for patients with haemophilia B and inhibitors. Although these nonfactor treatments offer great promise, further data and real-world evidence are needed.
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| 7. |
- Lambert, Thierry, et al.
(författare)
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Practical aspects of extended half-life products for the treatment of haemophilia
- 2018
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Ingår i: Therapeutic advances in hematology. - : SAGE Publications. - 2040-6207 .- 2040-6215. ; 9:9, s. 295-308
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Forskningsöversikt (refereegranskat)abstract
- Haemophilia A and haemophilia B are congenital X-linked bleeding disorders caused by deficiency of coagulation factor VIII (FVIII) and IX (FIX), respectively. The preferred treatment option for patients with haemophilia is replacement therapy. For patients with severe disease, prophylactic replacement of coagulation factor is the treatment of choice; this has been shown to reduce arthropathy significantly, reduce the frequency of bleeds and improve patients' quality of life. Prophylaxis with standard recombinant factor requires regular intravenous infusion at least two (FIX) to three (FVIII) times a week. Recombinant FVIII and FIX products with an extended half-life are in development, or have been recently licensed. With reported mean half-life extensions of 1.5-1.8 times that of standard products for FVIII and 3-5 times that of standard products for FIX, these products have the potential to address many of the unmet needs of patients currently treated with standard factor concentrates. For example, they may encourage patients to switch from on-demand treatment to prophylaxis and improve the quality of life of patients receiving prophylaxis. Indeed, extended half-life products have the potential to reduce the burden of frequent intravenous injections, reducing the need for central venous lines in children, promote adherence, improve outcomes, potentially allow for more active lifestyles and, depending on the dosing regimen, increase factor trough levels. Members of the Zürich Haemophilia Forum convened for their 19th meeting to discuss the practicalities of incorporating new treatments into the management of people with haemophilia. This review of extended half-life products considers their introduction in haemophilia treatment, including the appropriate dose and schedule of infusions, laboratory monitoring, patient selection, safety considerations, and the economic aspects of care.
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| 8. |
- Ljung, Rolf, et al.
(författare)
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Inhibitors in haemophilia A and B : Management of bleeds, inhibitor eradication, and strategies for difficult-to-treat patients
- 2019
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Ingår i: European Journal of Haematology. - : Wiley. - 1600-0609 .- 0902-4441. ; 102:2, s. 111-122
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Forskningsöversikt (refereegranskat)abstract
- The standard therapy for patients with haemophilia is prophylactic treatment with replacement factor VIII (FVIII) or factor IX (FIX). Patients who develop inhibitors against FVIII/FIX face an increased risk of bleeding, and the likelihood of early development of progressive arthropathy, alongside higher treatment-related costs. Bypassing agents can be used to prevent and control bleeding, as well as the recently-licensed prophylaxis, emicizumab, but their efficacy is less predictable than that of factor replacement therapy. Antibody eradication, by way of immune tolerance induction (ITI), is still the preferred management strategy for treating patients with inhibitors. This approach is successful in most patients, but some are difficult to tolerize and/or are unresponsive to ITI, and they represent the most complicated patients to treat. However, there are limited clinical data and guidelines available to help guide physicians in formulating the next treatment steps in these patients. This review summarizes currently available treatment options for patients with inhibitors, focussing on ITI regimens and those ITI strategies that may be used in difficult-to-treat patients. Some alternative, non-ITI approaches for inhibitor management are also proposed. This article is protected by copyright. All rights reserved.
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| 9. |
- Šalek, Silva Zupančić, et al.
(författare)
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Beyond stopping the bleed: short-term episodic prophylaxis with recombinant activated factor FVII in haemophilia patients with inhibitors.
- 2017
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Ingår i: Blood Transfusion. - 1723-2007. ; 15, s. 77-84
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Tidskriftsartikel (refereegranskat)abstract
- Preventing haemarthroses and arthropathy is a major challenge in patients with haemophilia and inhibitors, as treatment options are limited. One potential strategy is short-term episodic prophylaxis, which extends bypassing agent therapy beyond the resolution of bleeding to include the post-bleed inflammatory phase. At the 13(th) Zürich Haemophilia Forum, an expert panel reviewed the rationale behind this strategy, explored its current use with recombinant activated factor VII (rFVIIa) and considered treatment monitoring and optimisation. Two protocols are currently used for short-term episodic prophylaxis, both of which stipulate on-demand rFVIIa until resolution of bleeding, followed by daily dosing for ≥3 days to prevent re-bleeds. Short-term episodic prophylaxis should be individualised to optimise outcomes, perhaps through early treatment initiation or by combining rFVIIa with other treatments (e.g. factor VIII, tranexamic acid). Encouraging treatment compliance can also improve outcomes. Additionally, there is a need to develop objective clinical outcome measures, biomarkers and imaging protocols that can monitor treatment outcomes and joint disease in patients with inhibitors. A proactive approach incorporating a systematic package of care is needed. Currently, short-term episodic prophylaxis with rFVIIa may be an alternative treatment option to on-demand treatment for patients with inhibitors.
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| 10. |
- Santagostino, Elena, et al.
(författare)
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Switching treatments in haemophilia: is there a risk of inhibitor development?
- 2015
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Ingår i: European Journal of Haematology. - : Wiley. - 1600-0609 .- 0902-4441. ; 94:4, s. 284-289
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Forskningsöversikt (refereegranskat)abstract
- Patients with haemophilia A (and their physicians) may be reluctant to switch factor VIII (FVIII) concentrates, often due to concerns about increasing the risk of inhibitors; this reluctance to switch may contribute to patients missing the clinical benefits provided by the arrival of new factor VIII products. This topic was explored at the Eleventh Zurich Haemophilia Forum. Clinical scenarios for which product switching may be cause for concern were discussed; when there is a clinical need, there are no absolute contraindications to switching, but some patients (e.g. previously untreated patients and those undergoing elective surgery) may require more careful consideration. Both patient and physician surveys indicate that the reluctance to switch, and the fear of inhibitor development, does not appear to be evidence based. The evaluation of more recent data did not support previous studies suggesting that particular products (e.g. recombinant vs. plasma-derived and full length vs. B-domain modified) may be associated with increased risk. In addition, data from three national product switches showed that switching was not associated with increased inhibitor risk, but highlighted the need for regular inhibitor testing and for a centralised, unbiased database of inhibitor incidence. To conclude, current evidence does not suggest that switching products significantly influences inhibitor development.
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