0
selected
-
1.
Real-world case series and summary of current literature of infants and toddlers with severe hemophilia A with inhibitor on prophylaxis with emicizumab.
Garcia, J, Zia, A
Pediatric blood & cancer. 2021;(5):e28942
Abstract
Emicizumab is a recombinant, humanized, and a bispecific monoclonal antibody that bridges activated factor (F) IX and FX in place of FVIII to restore hemostasis in persons with hemophilia A (PHA). Data on the efficacy and safety of emicizumab in young children is limited. Immunologic naivety, physiologically decreased production of vitamin K dependent proteins, specifically FIX, and enhanced clearance of emicizumab in infants may support decreased emicizumab effectiveness. We report on the facilitation of care rendered by using emicizumab in young PHA with inhibitors and extend data on the efficacy and safety in PHA < 3 years.
-
2.
Haemophilic arthropathy: A narrative review on the use of intra-articular drugs for arthritis.
Buccheri, E, Avola, M, Vitale, N, Pavone, P, Vecchio, M
Haemophilia : the official journal of the World Federation of Hemophilia. 2019;(6):919-927
Abstract
INTRODUCTION Intra-articular injections of various drugs are commonly used in patients with degenerative osteoarthritis and also in haemophilic patients. Haemophilic arthropathy is a particular type of secondary osteoarthritis (OA), but the degeneration of strong synovial, cartilaginous and subchondral constituents is provoked by the direct action of iron and blood in the joint. AIM OF THE STUDY The aim of this study is to review the literature regarding the use of various intra-articular drugs in joints affected by haemophilic arthropathy. METHODS We reviewed the data from the literature; the search was performed on three medical electronic databases (PubMed, Cochrane Library and Scopus Web of Science) by three authors (B. E., A. M. and V. N.) from 3 December 2018 till 15 December 2018. The search string was as follows: (hyaluronic acid OR viscosupplementation OR platelet-rich plasma OR corticosteroid OR mesenchymal stem cells) AND (haemophilia OR haemophilic arthropathy OR haemophilic arthritis). RESULTS Once the research was performed, a total of 300 articles were identified. 47 selected articles were analysed by the reviewers, and the eligibility of the study inclusion was assessed independently. Twelve papers were included based on clear fulfilment of the inclusion criteria. Thirty-five articles were excluded for the following reasons: no full text or accessible data for 14 of them, 15 involved surgery or rehabilitation therapy as the primary topic and 6 were systematic reviews (the main topics were beyond the haemophilic arthropathy). CONCLUSION Although the degree of scientific evidence of the publications on intra-articular injections of various drugs (hyaluronic acid, corticosteriods, PRP and MSCs) in haemophilia is very low, it seems that intra-articular injections of hyaluronic acid can relieve joint pain for months and can be repeated every 6-12 months, which is why they can be recommended. Corticosteroid injections seem to relieve joint pain for a few weeks, but their routine use is not recommended in haemophilia. The efficacy of PRP and MSCs in haemophilic arthropathy is pending confirmation, which is why they are not currently recommended.
-
3.
Acquired haemophilia A in a patient with breast cancer and lung carcinoma: a case report and literature review.
Biesheuvel, V, Hiddema, SM, Levenga, H, Eikenboom, J, van der Deure, WM
The Netherlands journal of medicine. 2019;(4):153-155
Abstract
Acquired haemophilia A is a rare disorder caused by spontaneous formation of auto-antibodies (inhibitors) against coagulation factor VIII. This can lead tolife-threatening haemorrhages. Six to twenty-two percent of patients with acquired haemophilia have an underlying malignancy. We describe a 69-year-old woman with metastatic breast cancer and non-small cell lung carcinoma who presented at the emergency room with spontaneous bruising, and who was using a vitamin K antagonist. She had a prolonged activated partial thromboplastin time (aPTT) due to a coagulation factor VIII deficiency caused by factor VIII antibodies. She was treated with prednisone and cyclophosphamide.
-
4.
Joint disease in haemophilia: Pathophysiology, pain and imaging.
van Vulpen, LFD, Holstein, K, Martinoli, C
Haemophilia : the official journal of the World Federation of Hemophilia. 2018;:44-49
Abstract
Haemarthroses cause major morbidity in patients with haemophilia. Blood has devastating effects on all joint components, resulting in synovitis, osteochondral degeneration and ultimately end-stage haemophilic arthropathy. Key players in this process are iron and inflammation. Preventing joint bleeds is of utmost importance to maintain joint health as targeted therapies directed against blood-induced inflammation and iron-mediated processes are lacking. Joint bleeds result in acute pain as well as chronic pain due to synovitis or arthropathy. Acute pain originates from nociceptors activated by tissue damage. In chronic inflammation, central and peripheral sensitization of nociceptors might occur resulting in chronic pain. This also triggers a series of brain disorders such as emotional fear, anxiety, mood depression and impairment of cognitive functions. Treatment of haemophilia-related pain not only consists of analgesics, but also of exercise, education and in selected cases antidepressants and anticonvulsants. For objective assessment of joint structural outcome and detecting earlier changes of haemophilic arthropathy, both ultrasound (US) and magnetic resonance (MR) imaging have shown valuable. Both can be considered equally able to reveal signs of disease activity. MR imaging is able to visualize haemosiderin deposition and is more comprehensive in depicting osteochondral changes. Disadvantages of MR imaging are the duration of the examination, evaluation of a single joint at a time, costs and may require sedation, and it may need intraarticular contrast injection to depict initial osteochondral changes with accuracy. As such, US is a more useful screening tool and can be used for repeated follow-up examinations.
-
5.
Refining strategies to translate genome editing to the clinic.
Cornu, TI, Mussolino, C, Cathomen, T
Nature medicine. 2017;(4):415-423
Abstract
Recent progress in developing programmable nucleases, such as zinc-finger nucleases, transcription activator-like effector nucleases (TALENs) and clustered regularly interspaced short palindromic repeat (CRISPR)-Cas nucleases, have paved the way for gene editing to enter clinical practice. This translation is a result of combining high nuclease activity with high specificity and successfully applying this technology in various preclinical disease models, including infectious disease, primary immunodeficiencies, hemoglobinopathies, hemophilia and muscular dystrophy. Several clinical gene-editing trials, both ex vivo and in vivo, have been initiated in the past 2 years, including studies that aim to knockout genes as well as to add therapeutic transgenes. Here we discuss the advances made in the gene-editing field in recent years, and specify priorities that need to be addressed to expand therapeutic genome editing to further disease entities.
-
6.
Engineering less immunogenic and antigenic FVIII proteins.
Pratt, KP
Cellular immunology. 2016;:12-7
-
-
Free full text
-
Abstract
The development of neutralizing antibodies against blood coagulation factor VIII (FVIII), referred to clinically as "inhibitors", is the most challenging and deleterious adverse event to occur following intravenous infusions of FVIII to treat hemophilia A. Inhibitors occlude FVIII surfaces that must bind to activated phospholipid membranes, the serine proteinase factor IXa, and other components of the 'intrinsic tenase complex' in order to carry out its important role in accelerating blood coagulation. Inhibitors develop in up to one of every three patients, yet remarkably, a substantial majority of severe hemophilia A patients, who circulate no detectable FVIII antigen or activity, acquire immune tolerance to FVIII during initial infusions or else after intensive FVIII therapy to overcome their inhibitor. The design of less immunogenic FVIII proteins through identification and modification ("de-immunization") of immunodominant T-cell epitopes is an important goal. For patients who develop persistent inhibitors, modification of B-cell epitopes through substitution of surface-exposed amino acid side chains and/or attachment of bulky moieties to interfere with FVIII attachment to antibodies and memory B cells is a promising approach. Both experimental and computational methods are being employed to achieve these goals. Future therapies for hemophilia A, as well as other monogenic deficiency diseases, are likely to involve administration of less immunogenic proteins in conjunction with other novel immunotherapies to promote a regulatory cellular environment promoting durable immune tolerance.
-
7.
The Role of Angiogenesis in Haemophilic Arthropathy: Where Do We Stand and Where Are We Going?
Agapidou, A, Stavrakis, T, Vlachaki, E, Anagnostis, P, Vakalopoulou, S
Turkish journal of haematology : official journal of Turkish Society of Haematology. 2016;(2):88-93
Abstract
Haemophilia is an inherited bleeding disorder that can lead to degenerative joint arthropathy due to recurrent bleeding episodes affecting the musculoskeletal system of the patient. The cause of bleeding can be either traumatic or spontaneous. The pathogenesis of haemophilic arthropathy is unclear as many factors like iron, inflammatory cytokines, and angiogenic factors contribute to this process. Blood into joints can deteriorate the bone to such an extent that the patient experiences pain, reduction of the range of movement, and deformity of the joint, conditions that could have a great impact on quality of life. Over the years, management of haemophilic arthropathy has changed. Nowadays, early diagnosis with high resolution imaging like magnetic resonance imaging along with application of prophylaxis regimens can reduce the extent of damage to the joints. However, not all haemophilia patients have access to these interventions as cost may be prohibitive for some of them. The need for new, easy, and cost-effective strategies with the ability to identify early changes could be beneficial and could make a difference in the management of haemophilic arthropathy. Understanding the mechanism of processes like angiogenesis in the mechanism of developing arthropathy could be innovative for these patients and could help in the detection of new early diagnostic and therapeutic markers.
-
8.
Haemophilia A and B as a cause for secondary osteoporosis and increased fracture risk.
Anagnostis, P, Karras, S, Paschou, SA, Goulis, DG
Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis. 2015;(6):599-603
Abstract
Despite the increasing evidence regarding its association with low bone mineral density (BMD) both in adults and children, haemophilia A or B has not yet been considered among the classic causes of secondary osteoporosis. Although the exact mechanisms are not fully elucidated, physical inactivity and vitamin D deficiency seem to play a fundamental role for such an association. Viral infections and arthropathy further compromise bone mass. Except for low BMD, patients with haemophilia seem to be at increased risk for fracture and falls. The FRAX tool may be of value in this population, for the estimation of fracture risk. Regular exercise, prophylactic factor replacement therapy in severe haemophilia, fall prevention strategies and optimization of calcium and vitamin D intake are recommended. In any case, individualized multidisciplinary approach and careful assessment and management of fracture risk are recommended.
-
9.
Bone health in persons with haemophilia.
Kempton, CL, Antoniucci, DM, Rodriguez-Merchan, EC
Haemophilia : the official journal of the World Federation of Hemophilia. 2015;(5):568-77
Abstract
INTRODUCTION As the population of patients with haemophilia (PWH) ages, healthcare providers are required to direct greater attention to age-related co-morbidities. Low bone mineral density (BMD) is one such co-morbidity where the incidence not only increases with age, but also occurs with greater frequency in PWH. AIM: To review risk factors for low BMD, and strategies to promote bone health and identify patients who would benefit from screening for osteoporosis and subsequent treatment. METHODS A narrative review of the literature was performed in MEDLINE with keywords haemophilia, bone density, osteoporosis and fracture. Reference lists of retrieved articles were also reviewed. RESULTS Low BMD occurs more commonly in PWH than the general population and is most likely the result of a combination of risk factors. Steps to promote bone health include preventing haemarthrosis, encouraging regular exercise, adequate vitamin D and calcium intake, and avoiding tobacco and excessive alcohol intake. Adults 50 years of age and older with haemophilia and those younger than 50 years with a fragility fracture or increased fracture risk based on FRAX (The Fracture Risk Assessment Tool), regardless of haemophilia severity, should be screened for low BMD using dual x-ray absorptiometry (DXA). Once osteoporosis is diagnosed based on DXA, fracture risk should guide treatment. Currently, treatment is similar to those without haemophilia and most commonly includes bisphosphonates. CONCLUSION Haemophilia care providers should promote adequate bone formation during childhood and reduce bone loss during adulthood as well as identify patients with low BMD that would benefit from therapy.
-
10.
Radiosynovectomy: review of the literature and report from two haemophilia treatment centers.
Rampersad, AG, Shapiro, AD, Rodriguez-Merchan, EC, Maahs, JA, Akins, S, Jimenez-Yuste, V
Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis. 2013;(5):465-70
Abstract
Haemophilic arthropathy occurs due to recurrent bleeding into joints leading to swelling, inflammation, destruction of cartilage and bone, and development of arthritis. Although prophylactic replacement therapy assists in preventing arthropathy, it is not always adequate or affordable. Radiosynovectomy is a minimally invasive intervention for treatment of synovitis in haemophilic joints. The procedure utilises locally injected radioisotopes (Y, P, Rh) to ablate abnormal synovium with the goal of decreasing bleeding, slowing progression of cartilage and bone damage and preventing arthropathy. The objective of this review is to summarize the radiosynovectomy literature and to present patient outcomes associated with radiosynovectomy over the past 17 years from two haemophilia treatment centers (HTCs), one in the United States and one in Spain. Articles from these two centers support the current literature. A retrospective medical records review was performed by the two reporting HTCs on patients who underwent radiosynovectomy prior to 2009. Data review included: site of procedure, isotope utilized, bleeding frequency, and procedure complications. Radiosynovectomy is a cost-effective, minimally invasive, well tolerated procedure. As the paradigm for care in haemophilia shifts towards prevention of joint disease, the number of target joints with synovitis will likely decrease, except in patients who develop inhibitors. We propose early consideration of radiosynovectomy for patients with haemophilic synovitis prior to appearance of articular cartilage damage.