| 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. |
- Benson, Gary, et al.
(författare)
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Immune tolerance induction in patients with severe hemophilia with inhibitors: expert panel views and recommendations for clinical practice.
- 2012
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Ingår i: European Journal of Haematology. - : Wiley. - 1600-0609 .- 0902-4441. ; 88:5, s. 371-379
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Tidskriftsartikel (refereegranskat)abstract
- For hemophilia patients with inhibitors, immune tolerance induction (ITI) may help to restore clinical response to Factor (F) VIII or FIX concentrates. Several ITI regimens and protocols exist; however, despite 30 yr of progressive investigation, the ITI evidence base relies mainly on observational data. Expert opinion, experience, and interpretation of the available evidence are therefore valuable to support clinical decision-making. At the Sixth Zürich Haemophilia Forum an expert panel considered recent data and consensus to distill key practice points relating to ITI. The panel supported current recommendations that, where feasible, ITI should be offered early to children and adults (ideally ≤5 yr of inhibitor detection) when inhibitor titers are <10 Bethesda Units, and should be stopped when successful tolerance is achieved. For hemophilia A inhibitor patients, ITI can be founded on recombinant FVIII at high doses. The panel considered that patients with a high bleeding frequency should be offered additional prophylaxis with a bypassing agent. For hemophilia B patients, there may be a benefit to genetic testing to indicate the risk for inhibitors. ITI is often less effective and associated with a greater risk of side effects in these patients. For high-titer inhibitor (≥5 Bethesda Units) hemophilia B patients, the panel advised that bypassing agents could be offered on demand in addition to ITI. Within future ITI regimens there may be a role for additional immunosuppressant therapies. Participants agreed that research is needed to find alternatives to ITI therapy that offer durable and sustained effects and reduced rates of complications. © 2012 John Wiley & Sons A/S.
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| 4. |
- Berntorp, Erik, et al.
(författare)
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A systematic overview of the first pasteurised VWF/FVIII medicinal product, Haemate P/ Humate -P: history and clinical performance.
- 2008
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Ingår i: European Journal of Haematology. Supplementum. - : Wiley. - 0902-4506 .- 0902-4441 .- 1600-0609. ; 80:s70, s. 3-35
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Forskningsöversikt (refereegranskat)abstract
- Patients with von Willebrand disease (VWD) and haemophilia A (HA) lack, to varying degrees, the von Willebrand factor (VWF) and coagulation factor VIII (FVIII) that are critical for normal haemostasis. These conditions in turn make patients prone to uncontrolled bleeding. Historically, patients with severe forms of VWD or HA were crippled before adulthood and their life expectancy was significantly reduced. Over the past decades, specific coagulation factor replacement therapies including Haemate P, have been developed to help patients achieve and maintain normal haemostasis. Haemate P is a human, plasma-derived VWF/FVIII medicinal product, which was first licensed in Germany in 1981 for the treatment of HA-associated bleeding. It has since then come to be accepted as the gold standard for both the treatment and prophylaxis of bleeding in VWD, especially in cases where desmopressin [1-deamino-8-D-arginine vasopressin (DDAVP)] has been ineffective. Haemate P was the first effectively virus-inactivated (pasteurisation: 60 degrees C for 10 h in aqueous solution) FVIII product, whereby the risk of potentially threatening infective complications of plasma-derived products was reduced. Haemate P was also shown to have a VWF multimer profile remarkably close to that of normal plasma. This bibliographic review presents previously unpublished clinical data of Haemate P, based upon internal clinical study reports of the proprietor, CSL Behring, in addition to data already presented in other publications. The data demonstrate a predictable and well-characterised pharmacokinetic profile, and a proven record of short- and long-term safety, while effectively correcting the haemostatic defects in VWD and HA. Recently available data have also shown Haemate P to be of haemostatic value in exceptional clinical circumstances including surgical interventions. By virtue of its plasma-derived combination of VWF and FVIII, in addition to its high VWF:FVIII content ratio (2.4:1), Haemate P is also associated with successful immune tolerance induction in those patients developing inhibitor antibodies. Although the theoretical risk of thromboembolic complications does exist while receiving Haemate P, as it does with any FVIII replacement therapy, the incidence of such complications has remained notably low. Given the robust data that have accumulated for the use of Haemate P, dosing recommendations are also described in this review; the recommendations are tailored to patient-specific contexts including baseline VWF and FVIII levels in plasma and the type of surgical intervention being undertaken. A wide variety of studies have also provided data on paediatric and geriatric populations, all of which have suggested that Haemate P can be safely and effectively used in a wide variety of clinical circumstances.
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| 5. |
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| 6. |
- Gretenkort Andersson, Nadine, et al.
(författare)
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Intracranial haemorrhage in children and adolescents with severe haemophilia A or B - the impact of prophylactic treatment
- 2017
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Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048. ; 179:2, s. 298-307
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Tidskriftsartikel (refereegranskat)abstract
- The discussion of prophylactic therapy in haemophilia is largely focused on joint outcomes. The impact of prophylactic therapy on intracranial haemorrhage (ICH) is less known. This study aimed to analyse ICH in children with haemophilia, with a focus on different prophylaxis regimens and sequelae of ICH. We conducted a multicentre retrospective and prospective study that included 33 haemophilia centres from 20 countries. Inclusion criteria were children and adolescents born between 1993 and 2014, with severe haemophilia A or B without inhibitors. Participants were categorized by prophylaxis regimen: full, partial or none, based on dose and dose frequency of regular infusions. The cohort study included 1515 children: 29 cases of ICH over 8038 patient years were reported. The incidence of ICH in the prophylaxis group, 0·00033 cases of ICH/patient year, was significantly lower compared to the no prophylaxis group, 0·017 cases of ICH/patient year (RR 50·06; P < 0·001) and the partial prophylaxis group, 0·0050 cases of ICH/patient year (RR 14·92; P = 0·007). In the on-demand-group, 8% (2/24) children with ICH died and 33% had long-term sequelae, including intellectual and behavioural problems, paresis and epilepsy. Children on regular, frequent prophylaxis have a low risk of ICH compared to those using non-frequent or no prophylaxis.
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| 7. |
- 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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| 8. |
- 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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| 9. |
- Lambert, Thierry, et al.
(författare)
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Joint disease, the hallmark of haemophilia: What issues and challenges remain despite the development of effective therapies?
- 2014
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Ingår i: Thrombosis Research. - : Elsevier BV. - 1879-2472 .- 0049-3848. ; 133:6, s. 967-971
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Forskningsöversikt (refereegranskat)abstract
- Although effective therapies for haemophilia have been available for decades, the prevention and treatment of joint disease remain major clinical concerns for all haemophilia patients. Early identification of joint disease is vital to initiate or modify treatment, and prevent arthropathy. However, there remains a need for more sensitive and accurate methods, which may also detect improvement in patient outcome with new therapies or different prophylaxis regimens. These topics were explored at the Ninth Zürich Haemophilia Forum. A summary of our shared views on the limitations of current assessment methods, and the potential advantages of more recently developed tools, is provided. Ultrasonography enables more frequent routine monitoring and the early detection of joint disease. In addition, serological markers may provide suitable biomarkers of early arthropathy. To prevent arthropathy, in our opinion, prophylaxis is key to prevent joint bleeds and subsequent initiation of the 'vicious circle of joint disease'. However, issues remain, including when prophylaxis should be started, stopped, and if it is efficacious for inhibitor patients. Once joint bleeding has occurred, enhanced on-demand treatment should be considered. For more advanced stages of joint disease, the issues regarding the treatment options available are explored. Radiosynovectomy should be performed to treat chronic synovitis, and may prevent the need for elective orthopaedic surgery (EOS). Ultimately, however, EOS can be considered once all other treatment options have been explored. While, bypassing agents have facilitated the use of EOS in inhibitor patients, a multidisciplinary approach and careful surveillance is required for good patient outcome.
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| 10. |
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