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Journal of Thrombosis and Haemostasis :... Sep 2021Hemophilia A and B are rare X-linked inherited bleeding disorders caused by complete or partial deficiency in or the absence of coagulation factors VIII and IX.... (Review)
Review
Hemophilia A and B are rare X-linked inherited bleeding disorders caused by complete or partial deficiency in or the absence of coagulation factors VIII and IX. Recurrent joint bleeding (hemarthrosis) is the most frequent clinical manifestation of severe hemophilia. Unless appropriately managed, even subclinical hemarthrosis can lead to the development of hemophilic arthropathy, a disabling condition characterized by joint remodelling, chronic pain, and a reduced quality of life, and eventually requires joint replacement. Given the lack of specific treatments to reduce blood-induced synovitis, the prevention of bleeding is pivotal to the maintenance of joint health. Prophylactic coagulation factor replacement therapy using extended half-life recombinant drugs has significantly improved patients' quality of life by reducing the burden of intravenous injections, and the more recent introduction of nonreplacement therapies such as subcutaneous emicizumab injections has improved treatment adherence and led to the greater protection of patients with hemophilia A. However, despite these advances, chronic arthropathy is still a significant problem. The introduction of point-of-care ultrasound imaging has improved the diagnosis of acute hemarthrosis and early hemophilic arthropathy, and allowed the better monitoring of progressive joint damage, but further research into the underlying mechanisms of the disease is required to allow the development of more targeted treatment. In the meantime, patient management should be based on the risk factors for the onset and progression of arthropathy of each individual patient, and all patients should be collaboratively cared for by multidisciplinary teams of hematologists, rheumatologists, orthopedic surgeons, and physiotherapists at comprehensive hemophilia treatment centers.
Topics: Factor VIII; Hemarthrosis; Hemophilia A; Humans; Quality of Life; Synovitis
PubMed: 34197690
DOI: 10.1111/jth.15444 -
Knee Surgery, Sports Traumatology,... Mar 2021The posterior cruciate ligament (PCL) represents an intra-articular structure composed of two distinct bundles. Considering the anterior and posterior meniscofemoral... (Review)
Review
The posterior cruciate ligament (PCL) represents an intra-articular structure composed of two distinct bundles. Considering the anterior and posterior meniscofemoral ligaments, a total of four ligamentous fibre bundles of the posterior knee complex act synergistically to restrain posterior and rotatory tibial loads. Injury mechanisms associated with high-energy trauma and accompanying injury patterns may complicate the diagnostic evaluation and accuracy. Therefore, a thorough and systematic diagnostic workup is necessary to assess the severity of the PCL injury and to initiate an appropriate treatment approach. Since structural damage to the PCL occurs in more than one third of trauma patients experiencing acute knee injury with hemarthrosis, background knowledge for management of PCL injuries is important. In Part 1 of the evidence-based update on management of primary and recurrent PCL injuries, the anatomical, biomechanical, and diagnostic principles are presented. This paper aims to convey the anatomical and biomechanical knowledge needed for accurate diagnosis to facilitate subsequent decision-making in the treatment of PCL injuries.Level of evidence V.
Topics: Adult; Biomechanical Phenomena; Female; Hemarthrosis; Humans; Knee; Knee Injuries; Knee Joint; Ligaments, Articular; Magnetic Resonance Imaging; Male; Posterior Cruciate Ligament; Posterior Cruciate Ligament Reconstruction; Radiography; Recurrence; Rotation; Tibia; Young Adult
PubMed: 33201271
DOI: 10.1007/s00167-020-06357-y -
Blood May 2022
Topics: Animals; Anticoagulants; Arthritis; Hemarthrosis; Hematologic Diseases; Hemophilia A; Mice; Protein C
PubMed: 35511191
DOI: 10.1182/blood.2022015776 -
Journal of Clinical Medicine Jun 2017Spontaneous joint bleeding and repeated hemarthroses lead to hemophilic arthropathy-a debilitating disease with a significant negative impact on mobility and quality of... (Review)
Review
Spontaneous joint bleeding and repeated hemarthroses lead to hemophilic arthropathy-a debilitating disease with a significant negative impact on mobility and quality of life. Iron, cytokines, and angiogenic growth factors play a pivotal role in the onset of the inflammatory process that involves the synovial tissue, articular cartilage, and subchondral bone, with early damages and molecular changes determining the perpetuation of a chronic inflammatory condition. Synovitis is one of the earliest complications of hemarthrosis, and is characterized by synovial hypertrophy, migration of inflammatory cells, and a high degree of neo-angiogenesis with subsequent bleeding. The pathogenic mechanisms and molecular pathways by which blood in the joint cavity causes articular cartilage and subchondral bone destruction have yet to be fully elucidated. Both cytokines and matrix metalloproteinases and hydroxyl radicals may induce chondrocyte apoptosis. Members of the tumor necrosis factor receptor superfamily (such as the molecular triad: osteoprotegerin-OPG; receptor activator of nuclear factor κB-RANK; RANK ligand-RANKL) seem instead to play a major role in the inflammatory process. These pathogenic processes interact with each other and ultimately lead to a fibrotic joint and the disabling condition characteristic of hemophilic arthropathy.
PubMed: 28672826
DOI: 10.3390/jcm6070063 -
Journal of Thrombosis and Haemostasis :... Nov 2014
Topics: Coagulants; Disease Progression; Hemarthrosis; Hemophilia A; Hemophilia B; Humans; Predictive Value of Tests; Severity of Illness Index; Terminology as Topic; Treatment Outcome
PubMed: 25059285
DOI: 10.1111/jth.12672 -
British Journal of Haematology Jan 2023Marstacimab, an investigational human monoclonal antibody targeting tissue factor pathway inhibitor, demonstrated safety and efficacy in preventing bleeding episodes in...
Marstacimab, an investigational human monoclonal antibody targeting tissue factor pathway inhibitor, demonstrated safety and efficacy in preventing bleeding episodes in patients with haemophilia. This multicentre, open-label study investigated safety, tolerability, and efficacy of long-term weekly prophylactic marstacimab treatment in participants with severe haemophilia A and B, with or without inhibitors. Adult participants were enrolled from a previous phase Ib/II study or de novo and assigned to one of two subcutaneous (SC) marstacimab doses: once-weekly 300 mg or a 300-mg loading dose followed by once-weekly 150-mg doses, for up to 365 days. Study end-points included safety assessments and annualised bleeding rates (ABRs). Of 20 enrolled participants, 18 completed the study. Overall, 70% of participants had treatment-emergent adverse events, including injection site reactions, injection site haematoma, and haemarthrosis. No treatment-related serious adverse events or thrombotic events occurred. Across all dose cohorts, mean and median on-study ABRs ranged from 0 to 3.6 and 0 to 2.5 bleeding episodes/participant/year respectively, demonstrating comparable efficacy to that observed in the short-term parent study. No treatment-induced anti-drug antibodies were detected. Once-weekly SC marstacimab prophylaxis was well tolerated, with an acceptable safety profile, and maintained long-term efficacy up to 365 days. (Clinicaltrials.gov identifier, NCT03363321).
Topics: Adult; Humans; Hemophilia A; Antibodies, Monoclonal, Humanized; Hemorrhage; Hemarthrosis
PubMed: 36220152
DOI: 10.1111/bjh.18495 -
Reumatologia Clinica 2017
Topics: Adult; Animals; Ascorbic Acid; Feeding Behavior; Gingivitis; Hemarthrosis; Humans; Knee Joint; Magnetic Resonance Imaging; Male; Malnutrition; Milk; Schizophrenia, Paranoid; Scurvy; Yogurt
PubMed: 28433625
DOI: 10.1016/j.reuma.2017.03.001 -
Journal of Blood Medicine 2022Hemophilia is a congenital coagulopathy characterized by a deficiency of one of the clotting factors. It is characterized by the development of hematomas and... (Review)
Review
Hemophilia is a congenital coagulopathy characterized by a deficiency of one of the clotting factors. It is characterized by the development of hematomas and hemarthrosis, either spontaneously or after minor trauma. The recurrence of hemarthroses leads to progressive and degenerative joint damage from childhood (hemophilic arthropathy). This arthropathy is characterized by disabling physical effects that limit the functionality and quality of life of these patients. Medical progress achieved over the last decade in the drug treatment of hemophilia has improved the medium and long-term prospects of patients with more effective and long-lasting drugs. The universal use of safer, more effective and prolonged prophylactic treatments may promote the prevention of bleeding, and also therefore, of the development of hemarthrosis and joint damage. A number of imaging instruments have been developed for the assessment of hemarthrosis and hemophilic arthropathy, using ultrasound, magnetic resonance imaging and simple radiology. Different physical examination scores and questionnaires allow the assessment of joint health, self-perceived activity and functionality of patients with hemophilia. The approach to these patients should be interdisciplinary. Assessment of the processes that affect pain in these patients and the development of pain education models should be implemented. Expert advice and information to patients with hemophilia should be based on individual functional prevention diagnoses, advice on available therapies and sports practice, as well as health recommendations.
PubMed: 36277171
DOI: 10.2147/JBM.S343924