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Pediatric Blood & Cancer May 2021Hemophilia A and B are inherited hemorrhagic disorders that result from alterations in the coagulation cascade. Aside from spontaneous bleeding, the main complication of... (Review)
Review
Hemophilia A and B are inherited hemorrhagic disorders that result from alterations in the coagulation cascade. Aside from spontaneous bleeding, the main complication of hemophilia is hemarthrosis. Progress over the last three decades, specifically prophylaxis using recombinant factor, has prevented hemarthrosis and lengthened patient life expectancies. However, many treatments require frequent dosing up to three times a week, and alloantibodies (inhibitors) against replacement factor continues to be an issue. These problems call for novel treatments for patients with hemophilia. Although there has been progress in extended half-life factors and mimetics of factor VIII, an alternative treatment methodology is to rebalance the activities of pro- and anticoagulant factors through inhibition of the natural anticoagulants: antithrombin, tissue factor pathway inhibitor, protein C, and protein S. This review will explore the efficacy of targeting these inhibitory pathways from preclinical development through clinical trials, and delve into concerns of thrombotic risk.
Topics: Animals; Blood Coagulation; Coagulants; Hemophilia A; Humans
PubMed: 33577709
DOI: 10.1002/pbc.28934 -
The New England Journal of Medicine Aug 2007Effective ways to prevent arthropathy in severe hemophilia are unknown. (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
Effective ways to prevent arthropathy in severe hemophilia are unknown.
METHODS
We randomly assigned young boys with severe hemophilia A to regular infusions of recombinant factor VIII (prophylaxis) or to an enhanced episodic infusion schedule of at least three doses totaling a minimum of 80 IU of factor VIII per kilogram of body weight at the time of a joint hemorrhage. The primary outcome was the incidence of bone or cartilage damage as detected in index joints (ankles, knees, and elbows) by radiography or magnetic resonance imaging (MRI).
RESULTS
Sixty-five boys younger than 30 months of age were randomly assigned to prophylaxis (32 boys) or enhanced episodic therapy (33 boys). When the boys reached 6 years of age, 93% of those in the prophylaxis group and 55% of those in the episodic-therapy group were considered to have normal index-joint structure on MRI (P=0.006). The relative risk of MRI-detected joint damage with episodic therapy as compared with prophylaxis was 6.1 (95% confidence interval, 1.5 to 24.4). The mean annual numbers of joint and total hemorrhages were higher at study exit in the episodic-therapy group than in the prophylaxis group (P<0.001 for both comparisons). High titers of inhibitors of factor VIII developed in two boys who received prophylaxis; three boys in the episodic-therapy group had a life-threatening hemorrhage. Hospitalizations and infections associated with central-catheter placement did not differ significantly between the two groups.
CONCLUSIONS
Prophylaxis with recombinant factor VIII can prevent joint damage and decrease the frequency of joint and other hemorrhages in young boys with severe hemophilia A. (ClinicalTrials.gov number, NCT00207597 [ClinicalTrials.gov].).
Topics: Child; Child, Preschool; Drug Administration Schedule; Factor VIII; Follow-Up Studies; Hemarthrosis; Hemophilia A; Hemorrhage; Humans; Infant; Infusions, Intravenous; Joint Diseases; Male; Treatment Outcome
PubMed: 17687129
DOI: 10.1056/NEJMoa067659 -
American Journal of Blood Research 2021Hemophilia is a bleeding disorder characterized by the deficiency of a coagulation factors. The hemarthrosis is the most common and earliest manifestation. Repeated... (Review)
Review
Hemophilia is a bleeding disorder characterized by the deficiency of a coagulation factors. The hemarthrosis is the most common and earliest manifestation. Repeated hemarthrosis over time causes the development of hemophilic arthropathy. Among most involved joints, the ankle is the one where much uncertainty remains about the best course of action in managing the various degrees of hemophilia manifestations. These manifestations range from simple acute swelling and pain to devastating deformity. The purpose of our review is to draw a comprehensive picture of ankle hemophilic arthropathy epidemiology, pathophysiology, clinical symptoms and signs, radiological features and all the treatments available at present days. This review confirms that the first line of treatment considered should be the replacement therapy of the coagulation deficient factors that, preventing hemarthrosis, stops the development and progression of ankle's joint damage. The treatments proposed in literature for advanced stage of arthropathy are many and vary according to the severity of the case. They range from conservative ones such as physiotherapy, orthosis, intra-articular injections, laser therapy, external beam radiation therapy, radio-synovectomy and oral drug to invasive surgical treatment such as ankle arthrodesis and total ankle replacement. Whatever is the chosen treatment, according to the arthropathy severity we believe that it must be carried out in reference centers for foot and ankle surgery assisted by expert hematologists.
PubMed: 34322283
DOI: No ID Found -
Pain and Therapy Mar 2022Hemophilia is an inherited bleeding hematological disorder characterized by the partial or complete deficiency of clotting factor VIII or IX. Hemophilic arthropathy is... (Review)
Review
INTRODUCTION
Hemophilia is an inherited bleeding hematological disorder characterized by the partial or complete deficiency of clotting factor VIII or IX. Hemophilic arthropathy is the consequence of repeated joint bleeding (hemarthrosis) and its management is based on the prevention of acute bleeding through the administration of the deficient clotting factor concentrate or non-factor therapies. In addition, the management of acute and chronic pain is pivotal in hemophilic arthropathy in order to restore function and allow rehabilitation of the joint.
METHODS
We conducted a qualitative review of the literature regarding current and emerging strategies for pain treatment in hemophilic arthropathy. This review considers systemic and local pharmacological and non-pharmacological interventions for acute and chronic pain management.
RESULTS
In hemophilic arthropathy, pain management is based on analgesics such as paracetamol, which represents the first choice for acute and chronic pain in adults and children, in association with opioids for adults. Non-steroidal anti-inflammatory drugs inhibit platelet function, so that the currently preferred drugs are short courses of cyclooxygenase 2 inhibitors. Local treatment with intra-articular injections of corticosteroids is an option for refractory cases and physiotherapy has an important role after hemarthrosis and for the long-term management of chronic pain for both pediatric and adult patients.
CONCLUSIONS
The management of pain in hemophilia requires more standardization. Meanwhile, the safest drugs should be used at the lowest effective dosage and for periods as short as possible. For the non-pharmacological management of pain in these patients, a multidisciplinary team including hematologists, orthopedic surgeons, rheumatologists, and physiotherapists is warranted.
PubMed: 35020184
DOI: 10.1007/s40122-021-00345-x -
The Quarterly Journal of Nuclear... Dec 2022Radiosynoviorthesis (RSO) or radiation synovectomy has been practiced for more than half a century, but in many parts of the world, it is still relatively unknown and... (Review)
Review
Radiosynoviorthesis (RSO) or radiation synovectomy has been practiced for more than half a century, but in many parts of the world, it is still relatively unknown and not used to its full potential in the standard care for chronic, persistent or recurrent synovitis. The working mechanism of RSO is simple yet elegant. Radiopharmaceutical particles are, after injection in the affected synovial joint, gobbled up by phagocytizing subsynovial inflammatory cells. As a consequence, the synovium will be irradiated locally resulting in synovial cell necrosis and inhibition of cell proliferation, which eventually leads to a decrease in the inflammatory response in the joint cavity. In this review RSO is once again brought to the attention and common indications for RSO are discussed. Also, appropriate activities of the administrated radiopharmaceuticals and coadministrated glucocorticoids are provided. Furthermore, a detailed database-assisted chronological overview of published literature of RSO in inflammatory and non-inflammatory diseases, like rheumatoid arthritis, psoriatic arthritis, osteoarthritis and osteochrondomatosis, hemophilic hemarthrosis and pigmented villonodular synovitis (PVNS) is provided. Based upon the published literature an indication of level of evidence of RSO is discussed. There is evidence that RSO is effective in persistent synovitis in patients with a variety of causes for synovitis, although the effectiveness seems to decrease over time. In these patients, RSO may not be used to its full potential in many parts of the world. Results in of RSO in hemophilia patients with hemarthrosis are favourable, however the evidence for the effectiveness of RSO in these patients is less firm and mainly based on case series. The evidence for the efficacy of RSO as adjuvant therapy in PVNS is, at best, of very low quality.
Topics: Humans; Hemarthrosis; Synovitis, Pigmented Villonodular; Synovitis; Arthritis, Rheumatoid; Radiopharmaceuticals
PubMed: 35708601
DOI: 10.23736/S1824-4785.22.03470-7 -
The Cochrane Database of Systematic... Dec 2016Haemophilia is a bleeding disorder associated with haemorrhaging into joints and muscles. Exercise is often used to aid recovery after bleeds, and to improve joint... (Review)
Review
BACKGROUND
Haemophilia is a bleeding disorder associated with haemorrhaging into joints and muscles. Exercise is often used to aid recovery after bleeds, and to improve joint function in the presence of arthropathy.
OBJECTIVES
Our objective was to systematically review the available evidence on the safety and effectiveness of exercise for people with haemophilia.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Coagulopathies Trials Register and electronic databases PubMed, OVID-Embase, and CINAHL. We hand searched abstracts from congresses of the World Federation of Hemophilia and the European Hematology Association, trial registries and the reference lists of relevant articles.Date of the last search of the Cochrane Cystic Fibrosis and Genetic Disorders Group's Coagulopathies Trials Register: 14 December 2016.
SELECTION CRITERIA
Randomized or quasi-randomized controlled studies comparing any exercise intervention considered relevant in haemophilia management including supervised, unsupervised, aquatic, strengthening, aerobic or cardiovascular, stretching, proprioceptive and balance training exercise programs in males of any age with haemophilia A or B of any severity (those with co-morbidities were not excluded).
DATA COLLECTION AND ANALYSIS
Two authors reviewed the identified abstracts to determine their eligibility. For studies meeting the inclusion criteria, full articles were obtained. The two authors extracted data and assessed the risk of bias. Any disagreements were resolved by discussion. The authors contacted study investigators to obtain any missing data.
MAIN RESULTS
Eight studies were included, which represented 233 males with all severities of haemophilia A and B, ranging in age from eight years to 49 years. Study duration ranged from four to 12 weeks. Exercise interventions varied greatly and included resistance exercises, isometric exercises, bicycle ergometry, treadmill walking and hydrotherapy; therefore, comparison between studies was difficult.None of the studies measured or reported adverse effects from the interventions. None of the studies reported outcomes regarding bleed frequency, quality of life or aerobic activity. Overall risk of bias across all studies was assessed as unclear.Very few studies provided sufficient information for comparison. None of the studies reported data that favoured the control group. One study reported that six weeks of resistance training improved joint health status (Colorado score) compared to controls. The addition of pulsed electromagnetic fields also improved ankle scores compared to exercises alone, but this was not seen in the elbows or knees.Two studies reported statistically significant improvements in pain intensity after exercise interventions compared to controls. Hydrotherapy exercises produced significant decreases in pain compared to controls and land-based exercise groups.Two studies found improvement in joint motion in the exercise group compared to controls. One study compared land- and water-based exercises; there was no difference in the range of motion between the two groups; however, the water-based exercise group did show improvement over the control group.One study, comparing joint traction and proprioceptive neuromuscular facilitation for the elbow to a control group, showed no differences in biceps girth or strength after 12 weeks of intervention.Some studies reported comparisons between interventions. In one study, treadmill training significantly improved balance in children compared to bicycle ergometry. Another study added partial weight bearing exercises to quadriceps exercises and showed improved walking tolerance.Four studies evaluated quadriceps or hamstring strength (or both). The addition of bicycle ergometry and exercises with weights was more effective than static exercises and treadmill walking for strengthening knee flexors and extensors. Partial weight-bearing exercises through range were more effective than static and short arc exercises for improving knee extensor strength. The addition of treadmill walking to ultrasound, stretching and strengthening exercises showed increased peak torque of knee flexors and extensors and decrease in knee effusion.The results should be interpreted with caution due to the quality of evidence (GRADE) as outlined in the summary of findings tables, which demonstrates that all but one of the outcomes assessed were rated as low or very low due to the small sample sizes and potential bias.
AUTHORS' CONCLUSIONS
These results must be considered with caution. There is a lack of confidence in the results due to the small number of included studies and the inability to pool the results due to the heterogeneity of outcome measures. Most exercise interventions produced improvement in one or more of the measured outcomes including pain, range of motion, strength and walking tolerance. Hydrotherapy may be more effective than land exercises for pain relief in adults. Functional exercises such as treadmill walking and partial weight bearing exercises seem to be more effective than static or short arc exercises for improving muscle strength. These findings are consistent with the many non-controlled intervention reports in the haemophilia literature. No adverse effects were reported as a result of any of the interventions. However, some groups used prophylactic factor prior to exercise and other groups studied only subjects with moderate haemophilia. Therefore, the safety of these techniques for persons with severe haemophilia remains unclear.
Topics: Adolescent; Adult; Child; Exercise Therapy; Hemarthrosis; Hemophilia A; Hemophilia B; Humans; Hydrotherapy; Male; Middle Aged; Muscle Strength; Muscle Stretching Exercises; Pain; Pain Measurement; Randomized Controlled Trials as Topic; Range of Motion, Articular; Resistance Training
PubMed: 27992070
DOI: 10.1002/14651858.CD011180.pub2 -
Journal of Blood Medicine 2014Hemophilia is a hematological disorder characterized by a partial or complete deficiency of clotting factor VIII or IX. Its bleeding complications primarily affect the... (Review)
Review
Hemophilia is a hematological disorder characterized by a partial or complete deficiency of clotting factor VIII or IX. Its bleeding complications primarily affect the musculoskeletal system. Hemarthrosis is a major hemophilia-related complication, responsible for a particularly debilitating chronic arthropathy, in the long term. In addition to clotting factor concentrates, usually prescribed by the hematologist, managing acute hemarthrosis and chronic arthropathy requires a close collaboration between the orthopedic surgeon and physiotherapist. This collaboration, comprising a coagulation and musculoskeletal specialist, is key to effectively preventing hemarthrosis, managing acute joint bleeding episodes, assessing joint function, and actively treating chronic arthropathy. This paper reviews, from a practical point of view, the pathophysiology, clinical manifestations, and treatment of hemarthrosis and chronic hemophilia-induced arthropathy for hematologists, orthopedic surgeons, and physiotherapists.
PubMed: 25378964
DOI: 10.2147/JBM.S50644 -
International Journal of Molecular... Oct 2020Hemophilia A and B are X-linked congenital bleeding disorders characterized by recurrent hemarthroses leading to specific changes in the synovium and cartilage, which... (Review)
Review
BACKGROUND
Hemophilia A and B are X-linked congenital bleeding disorders characterized by recurrent hemarthroses leading to specific changes in the synovium and cartilage, which finally result in the destruction of the joint: this process is called hemophilic arthropathy (HA). This review highlights the most prominent molecular biomarkers found in the literature to discuss their potential use in the clinical practice to monitor bleeding, to assess the progression of the HA and the effectiveness of treatments.
METHODS
A review of the literature was performed on PubMed and Embase, from 3 to 7 August 2020. Study selection and data extraction were achieved independently by two authors and the following inclusion criteria were determined a priori: English language, available full text and articles published in peer-reviewed journal. In addition, further articles were identified by checking the bibliography of relevant articles and searching for the studies cited in all the articles examined.
RESULTS
Eligible studies obtained at the end of the search and screen process were seventy-three (73).
CONCLUSIONS
Despite the surge of interest in the clinical use of biomarkers, current literature underlines the lack of their standardization and their potential use in the clinical practice preserving the role of physical examination and imaging in early diagnosis.
Topics: Biomarkers; Genes, X-Linked; Hemarthrosis; Hemophilia A; Hemophilia B; Hemorrhage; Humans; Joint Diseases; Synovial Membrane
PubMed: 33023246
DOI: 10.3390/ijms21197292 -
Frontiers in Medicine 2022Knee injuries such as anterior cruciate ligament ruptures and meniscal injury are common and are most frequently sustained by young and active individuals. Knee injuries... (Review)
Review
Knee injuries such as anterior cruciate ligament ruptures and meniscal injury are common and are most frequently sustained by young and active individuals. Knee injuries will lead to post-traumatic osteoarthritis (PTOA) in 25-50% of patients. Mechanical processes where historically believed to cause cartilage breakdown in PTOA patients. But there is increasing evidence suggesting a key role for inflammation in PTOA development. Inflammation in PTOA might be aggravated by hemarthrosis which frequently occurs in injured knees. Whereas mechanical symptoms (joint instability and locking of the knee) can be successfully treated by surgery, there still is an unmet need for anti-inflammatory therapies that prevent PTOA progression. In order to develop anti-inflammatory therapies for PTOA, more knowledge about the exact pathophysiological mechanisms and exact course of post-traumatic inflammation is needed to determine possible targets and timing of future therapies.
PubMed: 36072956
DOI: 10.3389/fmed.2022.973870 -
The American Journal of Managed Care Mar 2015Hemophilia is characterized by genetic mutations resulting in the deficiency of factors critical to the normal process of coagulation, sometimes resulting in spontaneous... (Review)
Review
Hemophilia is characterized by genetic mutations resulting in the deficiency of factors critical to the normal process of coagulation, sometimes resulting in spontaneous bleeding into soft tissue, joints, and internal organs. The 2 most common subtypes are hemophilia A, or factor VIII deficiency, and hemophilia B, or factor IX deficiency. Hemophilia affects an estimated 20,000 individuals in the United States. The diagnosis and management of patients with severe hemophilia is complex, and requires preventive treatment (prophylaxis) to avoid bleeding episodes and related complications and the use of replacement therapy with coagulation factors during acute bleeding episodes. To achieve optimal long-term results, the treatment of patients with hemophilia requires a comprehensive approach coordinated by a multidisciplinary team of specialists. Hemophilia imposes a substantial burden from economic, societal, and patient perspectives.
Topics: Antibodies; Blood Coagulation Factors; Factor VIII; Factor XI; Hemarthrosis; Hematoma; Hemophilia A; Hemophilia B; Humans; Patient Care Team
PubMed: 26168206
DOI: No ID Found