Recurrent Hemarthrosis Research Articles

Early Outcome of a Contemporary Unicondylar Knee System.

In 2019, a new fixed-bearing implant for unicondylar knee arthroplasty (UKA) was introduced that incorporated a round-on-flat design featuring an Oxinium femoral component coupled with a highly crosslinked polyethylene bearing surface. Compared to prior implants, the design featuredsmaller size increments coupled with medial and lateral-specific tibial baseplates. The objective of this study is to describe our institution's early experience with this UKA implant system by evaluating survivorship, reasons for revision, and patient-reported outcome measures (PROMs). The 944 UKAs that comprise the study population, including 814 medial and 130 lateral joint replacements, were performed by six surgeons from September 2019 through the end of December 2023. All UKA components were cemented, the mean age at surgery was 67.1±10.0 years, 57% (537/944) of the UKAs were performed among women, and the mean body mass index was 30.3±6.2 kg/m2. Outcome measures included Kaplan-Meier survivorship using reoperation for any reason as an endpoint, reasons for reoperation, range of motion, and PROMs that were collected preoperatively and postoperatively at 4 weeks, 4 months, 1 year, and 2 years. Using reoperation for any reason as an endpoint, 1-year survivorship was 99.3% (95% CI, 98.7 to 99.9%) and 2-year survivorship was 98.2% (95% CI, 96.9 to 99.5%). There were nine reoperations among the 944 UKAs, including three for infection, two for tibial loosening, one for femoral loosening, one for progression of arthritis, one for patellar instability, and one for recurrent hemarthrosis. The mean time to reoperation was 0.82±0.68 years and all were performed among medial UKAs. Range of motion increased from 117±8 degrees preoperatively to 122±6 degrees at 1-year follow-up. PROMs, including the Knee Injury and Osteoarthritis Outcome Score for Joint Replacement (KOOS JR) and the Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health Physical score, demonstrated progressive increases from the preoperative assessment through 2-year follow-up. For UKAs with preoperative and 2-year KOOS JR scores, the mean change was 31±17. As new implants and technologies are introduced, documenting the early outcome from high volume centers can offer valuable insights to validate the effectiveness of implant systems before they are adopted by the broader orthopedic community. This study demonstrates encouraging early outcome data associated with a contemporary UKA system based on survivorship and PROMs. At this early stage, there are no implant-related concerns but obtaining additional follow-up will be important to quantify how revisions and PROMs evolve over time.

Patient Experience With Efanesoctocog Alfa for Severe Hemophilia A: Results From the XTEND-1 Phase 3 Clinical Study Exit Interviews

PurposeHemophilia A is a rare bleeding disorder that leads to recurrent hemarthrosis, which can ultimately result in reduced mobility and poor quality of life. Qualitative exit interviews provide insights into patient perspectives and support the interpretation of quantitative trial data, such as patient-reported outcome measures. In the Phase 3 XTEND-1 study (NCT04161495) of efanesoctocog alfa in participants with severe hemophilia A, exit interviews were conducted to understand pre- and post-study experiences with pain and physical functioning and to evaluate participants’ treatment experiences. MethodsIn XTEND-1, participants (≥12 years old) received once-weekly efanesoctocog alfa prophylaxis 50 IU/kg for 52 weeks (Arm A) or on-demand efanesoctocog alfa 50 IU/kg for 26 weeks followed by 26 weeks once-weekly prophylaxis (50 IU/kg; Arm B). Optional qualitative exit interviews were conducted using a semi-structured guide in a subset of participants following study completion. Interviews included open-ended questions about participants’ pre- and post-study experiences with hemophilia A and targeted questions relating to improvements in patient-reported outcomes assessed during XTEND-1, including the Haemophilia Quality of Life Questionnaire for Adults Physical Health subscale (Haem-A-QoL PH). Content validity of the Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Intensity 3a measure was also assessed, particularly the worst pain item. FindingsExit interviews were conducted with 29 of 159 patients enrolled in XTEND-1 (mean [range] age 40 [16−73] years). Of 17 participants enrolled in Arm A, 13 (76.5%) reported a “wearing off” feeling with pre-study treatment, including more aches/pain, breakthrough bleeds, and limited physical activities. Joint pain was the most reported pre-study symptom (96.6%; n = 28/29), followed by a reduced ability to move without pain (89.7%, n = 26/29). Improvements following efanesoctocog alfa prophylaxis in ≥1 Haem-A-QoL PH domain were reported by 89.7% (n = 26/29) of participants, with improvements in joint pain, the ability to move without pain, and painful swellings reported by at least 21 (84%) participants. Participants reported that the PROMIS Pain Intensity 3a items were relevant, clear, and easy to answer. Most participants (96.6%) were “quite satisfied” or “very satisfied” with efanesoctocog alfa prophylaxis. All participants preferred efanesoctocog alfa over pre-study treatment. ImplicationsThe exit interviews demonstrated that once-weekly efanesoctocog alfa prophylaxis resulted in patient-relevant and meaningful improvements in pain and physical functioning, consistent with the quantitative findings from XTEND-1. These results support the validity of the Haem-A-QoL PH and PROMIS Pain Intensity 3a assessed during XTEND-1, demonstrating the potential for change with efficacious treatment. Trial RegistryClinicalTrials.gov Trial Registration NumberNCT04161495 Registry URLhttps://clinicaltrials.gov/study/NCT04161495

Stability, Balance, and Physical Variables in Patients with Bilateral Hemophilic Arthropathy of the Ankle versus Their Healthy Peers: A Case-Control Study.

(1) Background: The recurrence of hemarthrosis in patients with hemophilia triggers a pathophysiological process of degenerative, progressive, and irreversible joint destruction. This hemophilic arthropathy is characterized by chronic pain, muscle atrophy, loss of mobility, and proprioceptive alterations. As the same joint undergoes repeated hemarthrosis, the function of the mechanical receptors deteriorates, causing a pathophysiological modulation and deterioration of the musculoskeletal system. The objective was to analyze the differences in stability and balance, as well as in ankle dorsal flexion, functionality, and muscle strength, between patients with bilateral hemophilic arthropathy and their healthy peers. (2) Methods: A cross-sectional descriptive case-control study was performed. Twenty-two participants were recruited: 10 adult patients with bilateral hemophilic arthropathy of the knee and ankle and 12 healthy subjects. The variables were balance (Rs Scan pressure platform), ankle dorsiflexion range of motion (Leg Motion), functionality (2-Minute Walk Test), and ankle dorsal strength (dynamometry). (3) Results: Statistically significant differences (p < 0.05) were found in the balance without visual support in the Max-Y variable (MD = 2.83; CI95%: 0.33;5.33; Effect size (d) = 0.67), ankle dorsiflexion (MD = 16.00; CI95%: 14.30; 20.0; d = 7.46), and strength of the ankle flexor muscles (MD = 128.50; CI95%: 92.50; 153.60; d = 2.76). (4) Conclusions: Ankle range of motion in dorsal flexion, functionality, and muscle strength in dorsal flexion is poorer in patients with bilateral lower limb hemophilic arthropathy than in their healthy peers. Patients with bilateral hemophilic ankle arthropathy have statistically poorer stability and balance without visual support than their healthy peers.

Anesthetic considerations for joint replacement surgery in hemophilic arthropathy: a comprehensive review.

Managing hemophilia in patients undergoing joint replacement surgery requires a comprehensive approach encompassing preoperative assessment, meticulous intraoperative care, and tailored postoperative management. Evaluation of joint integrity, bleeding history, and inhibitor presence guides surgical planning and hemostatic therapy selection to optimize outcomes. During surgery, careful attention to factor replacement, antibiotic prophylaxis, anesthetic techniques, and orthopedic strategies minimizes bleeding risk and enhances surgical success. Postoperatively, effective pain management, continued hemostatic therapy, and individualized rehabilitation programs are vital for facilitating recovery and preventing complications. Close monitoring for potential complications, such as periprosthetic joint infection and recurrent hemarthrosis, allows for prompt intervention when necessary. Overall, a collaborative approach involving hematologists, orthopedic surgeons, anesthesiologists, and rehabilitation specialists ensures comprehensive care tailored to the unique needs of patients with hemophilia undergoing joint replacement surgery, ultimately optimizing outcomes and improving quality of life. This holistic approach addresses the multifaceted challenges posed by hemophilia and joint replacement surgery, providing patients with the best possible chance for successful outcomes and long-term joint function. By integrating specialized expertise from multiple disciplines and implementing evidence-based strategies, healthcare providers can effectively manage hemophilia in the context of joint replacement surgery, mitigating risks and maximizing benefits for patients.

Stromal cell-derived factor 1 alpha (SDF-1alfa) and cartilage oligomeric matrix protein (COMP): Two potential signature biomarkers of radiological detectable hemophilic arthropathy.

Hemophilia is a rare constitutional bleeding disorder due to a deficiency in Factor VIII or Factor IX. Recurrent hemarthroses, one of the major complications of the disease, lead to hemophilic arthropathy, a disabling condition that requires early diagnosis. Traditionally, clinical examination and plain film radiography have been used to diagnose hemophilic arthropathy. Magnetic resonance imaging (MRI) and ultrasound can be more useful for diagnosing soft-tissue changes. However, but each of these methods has limitations and diagnosis of arthropathy can be delayed. The aim of this project was to assess plasmatic biomolecules indicative of osteo-cartilaginous damage in patients with hemophilia with or without known arthropathy, in order to improve the diagnosis of this major complication of the disease. In this monocentric retrospective study, 40 patients with hemophilia A or B, for whom a plasma sample was available, provided informed consent for further analyses (multiplex immunoassays and ELISA) and collection of relevant clinical information in their medical files. Correlations were sought for between biomarkers of interest and the severity of joint lesions assessed according to Pettersson's radiologic score. Two biomarkers were identified, respectively SDF-1α and COMP. Their plasmatic levels were significantly increased in patients with arthropathy compared to controls and patients without arthropathy. These values correlated significantly with the Pettersson score in patients under regular prophylaxis. Two plasma biomarkers have been identified that could help assess the presence and severity of hemophilic arthropathy.

Non-surgical correction of knee flexion deformity in persons with haemophilia: A staged multidisciplinary approach.

Flexion deformity of the knee is a common complication following recurrent haemarthrosis in persons with haemophilia (PWH) on episodic factor replacement therapy, restricting independent mobility. There is limited literature on the comprehensive management of this condition. This report provides the outcome of a staged multidisciplinary approach for the correction of knee flexion deformity (KFD) even in limited resource settings. The data of 49 consecutive PWH who were treated for KFD were analysed. The approach included graded physical therapy (PT), followed by serial casting and/or mobilisation under anaesthesia (MUA). MUA was done in carefully selected knees. Surgical correction was opted when non-surgical methods failed. Of the 49 patients (55 knees), with a median KFD of 40 degrees (range: 10-90), 26/55 (47%) were corrected by graded PT. With serial casting, 9/19 (47%) knees had their KFD corrected. MUA was done for 11 knees of which five achieved correction (45%). Surgical correction was required for only seven knees (12.7%). Following this approach, KFD improved from 40 degrees (range: 10-90) to 15 degrees (range: 0-40), with only minor loss of flexion from 105 (range: 60-155) to 90degrees (range: 30-150). Out of 55 KFD, 46 (83.6%) KFD were corrected; non-surgical, 39 (70.9%) and surgery, seven (12.7%). The remaining patients (nine KFD; 16.4%) were able to achieve their functional goal despite not meeting the correction criteria. This study shows that in PWH, functionally significant KFD correction can be achieved in about 71%, through non-surgical methods, even without prophylactic factor replacement.

Predicting the development of hemophilic arthropathy in patients with hemophilia based on patient age: a retrospective single-center database study

ABSTRACT Background Patients with hemophilia (PWH) develop hemophilic arthropathy of the major joints due to recurrent hemarthrosis. This study retrospectively estimated the age at which PWH may expect to develop hemophilic arthropathy and undergo joint replacement surgery. Research design and methods Using retrospective data from PWH at a Czech orthopedic center, Kaplan Meier analyses were used to estimate the cumulative proportions of patients with hemophilic arthropathy and undergoing joint replacement surgery as a function of age. Results Based on 1028 joint examinations in 167 PWH, hemophilic arthropathy of the knees, elbows, ankles and hips was estimated to develop by a median age of 48, 51, 52 and 61 years, respectively, with ≈80% of patients having such damage by ≈70 years of age. Hemophilic arthropathy of the shoulder occurred much later (median >80 years). In patients undergoing knee or hip replacement surgery, hemophilic arthropathy of the knee and hip occurred at a median age of ≈50 and ≈60 years, respectively, with replacement surgery occurring at a median of ≈70 and >75 years. Conclusions In PWH, the risk of developing hemophilic arthropathy accumulates continuously over the patient’s lifetime, allowing predictions about the ages at which such damage and joint replacement surgery may occur.

Stromal Cell-Derived Factor 1 Alpha (SDF-1α), Cartilage Oligomeric Matrix Protein (COMP) and Circulating microRNAs 208a-3p and 221-3p: Potential Signature Biomarkers of Hemophilic Arthropathy

Introduction. Hemophilia A is a rare constitutional bleeding disorder due to a deficiency in Factor VIII. Recurrent hemarthroses, one of the major complications of the disease, lead to hemophilic arthropathy, a disabling condition difficult to diagnose with current strategies (ultrasound and magnetic resonance imaging [MRI]), with possible delayed diagnosis. MRI, the gold standard, is not of easy access nor cheap and requires sedation in young children. Ultrasound is liable to inter-operator variability and difficult to apply to such joints as ankles, especially in children for whom this is the most frequently involved location of hemophilic arthropathy. Circulating MicroRNAs are a group of endogenous, small, non-coding RNA molecules that regulate gene expression ; and knowledge on the potential roles of miRNAs in haemophilia is very limited. Aim. The aim of this project was to assess plasmatic biomolecules indicative of osteo-cartilaginous damage in patients with hemophilia with or without known arthropathy, in order to improve the diagnosis of this major complication of the disease. We also investigated microRNA expression in patients with haemophilia A with and without inhibitors, compared to healthy controls. Methods In this monocentric retrospective study, 40 patients with hemophilia A or B, for whom a plasma sample was available, provided informed consent for further analyses (multiplex immunoassays and ELISA) and collection of relevant clinical information in their medical files. Correlations were sought for between biomarkers of interest and the severity of joint lesions assessed according to Pettersson radiologic score. For miRNAs analysis, all RNAs were extracted from plasma samples. We synthesised complementary DNA from the RNA samples, and used to quantitative PCR and microarray analysis to allow us to look at changes in expression levels. Results Two biomarkers were identified, respectively SDF-1α and COMP. Their plasmatic levels were significantly increased in patients with arthropathy compared to controls and patients without arthropathy. These values correlated significantly with the Pettersson score in patients under regular prophylaxis. We also identified two microRNAs of interest, the microRNA 208a-3p was significantly downregulated in hemophilia patients with arthropathy but not in patients without arthropathy and the microRNA 221-3p had a clear tendency for statistically significant down regulation in hemophiliacs with arthropathy. Interestingly, miRNA 221-3p has been shown to be involved in rheumatoid arthritis. Dysregulation of this microRNA leads to a reduced anti-inflammatory response and drives macrophages into a pro-inflammatory state. Conclusion Two plasma proteins SDF-1 alfa and COMP and two circulating micro-RNAs have been identified as potential biomarkers that could help physicians to assess the presence and severity of hemophilic arthropathy.

Experiences with Efanesoctocog Alfa: Exit Interviews with Caregivers of Previously Treated Patients with Hemophilia A from the XTEND-Kids Phase 3 Clinical Trial

Introduction Hemophilia A is a rare, genetic bleeding disorder that leads to recurrent hemarthrosis, causing debilitating pain and joint deterioration, and ultimately results in reduced mobility and a poor quality of life. The aim of this study was to gain insight into caregivers' perspectives on the impact of hemophilia and its treatment as well as experiences with efanesoctocog alfa prophylaxis, by conducting optional qualitative exit interviews with caregivers of children with severe hemophilia A exiting the XTEND-Kids study. Methods XTEND-Kids (NCT04759131) was a Phase 3, open-label, multicenter study evaluating the safety, efficacy, and pharmacokinetics of once-weekly efanesoctocog alfa (50 IU/kg) for 52 weeks, in previously treated children aged &amp;lt;12 years with severe hemophilia A. Semi-structured exit interviews were conducted with caregivers of children from 12 clinical sites across four countries (Canada, France, United Kingdom, and the United States) at their 52-week end-of-treatment (EOT) visit and before end-of-study (EOS) was declared. All caregivers of children across these countries were given the option of participating in the exit interviews. In addition to open-ended questions about the caregiver and their child's experience with hemophilia A, more targeted questions relating to hemophilia-related symptoms and experience with treatments before and during the XTEND-Kids study were queried (Yes/No; Likert Scale). Interviews were conducted by experienced moderators in each country's native language using translated guides where applicable and lasted approximately 60 minutes. Interviews were audio recorded and transcribed for analysis. Descriptive statistics of select items from the qualitative data were computed and summarized. Results Seventy-two children completed their Week 52 EOT or EOS visit; 19 caregivers (18 mothers; 1 father) of 20 children completed exit interviews (one caregiver was the parent of two children in the study). Mean (SD) age of the children was 6.5 (3.1) years, and all were male. All children were receiving FVIII replacement prophylaxis prior to study entry, except for one in the 6 to &amp;lt;12 years of age cohort who was receiving an on-demand regimen. Regarding pre-study treatment experiences, nine caregivers (47.4%) reported that their child's bleeds had a negative impact on their own day-to-day life and eight caregivers (42.1%) reported their child's bleeds had a negative impact on their own mood and emotions . According to caregivers, the most significant impact of hemophilia A and its treatment on their children was on mood and emotions (n=19/20 children; 95.0%) and their physical health/activity (n=14/20 children; 70.0%). When queried about what bothered their children most about their hemophilia and its treatment pre-study, caregivers reported that six children were most bothered about being more cautious or less active than other children due to their condition and 12 children were most bothered about the number of treatment infusions per week. In the XTEND-Kids study, all caregivers (n=19; 100%) reported at least one improvement in their child as a result of efanesoctocog alfa prophylaxis, with eight caregivers (40.0%) stating their child had longer or better protection due to higher factor levels. All caregivers (n=19; 100%) reported noticing a positive effect on their child's daily life and functioning, with most caregivers (n=18; 94.7%) reporting that treatment with efanesoctocog alfa had improved their child's mood and emotions (Figure 1). Efanesoctocog alfa prophylaxis also led to positive changes in caregivers' daily life and functioning, with improvements (out of those who reported the impact at baseline) seen by caregivers in managing treatment (n=16; 100%), impact on family (n=11; 100%), mood/emotions (n=15; 93.8%), and work (n=11; 91.7%) (Figure 2). All caregivers (n=19; 100%) preferred efanesoctocog alfa over their children's previous hemophilia treatment; 18 (94.7%) were “very satisfied”, with one (5.3%) caregiver “satisfied”. Conclusion Caregivers of children with severe hemophilia A reported major impacts at study baseline on both daily life and functioning with prior treatments. Efanesoctocog alfa prophylaxis provided improvements in both children and their caregiver's daily life and functioning, and all caregivers preferred efanesoctocog alfa to their child's previous treatment.

Incidence of Postoperative Venous Thromboembolism, Hemorrhage, and Infection in Patients with Bleeding Disorders after Hip and Knee Arthroplasty

Introduction: Patients undergoing hip or knee arthroplasty (HA or KA) developed asymptomatic postoperative (post-op) venous thromboembolism (VTE) in around 30% of cases without any pharmacologic thromboprophylaxis (ThPPx). The use of pharmacological ThPPx after HA or KA has reduced the incidence of post-op VTE within 90 days to around 0.6-1.5%. People with bleeding disorders tend to have chronic joint damage from recurrent hemarthroses and frequently require HA or KA. This was especially true in the era before chronic factor prophylaxis. The exact risk estimate of post-op VTE in this population is unclear. Furthermore, the exact risk benefit for pharmacologic ThPPx is also unknown. Methods: A retrospective cohort study was conducted by looking at patients who underwent HA or KA and stratifying them based upon whether they had bleeding disorder diagnosis. Data was collected from the Health Facts database, which contains de-identified information from the electronic medical records of all US hospitals in which Cerner© has a data use agreement. Patients with bleeding disorders included Hemophilia A, B, C and Von Willebrand disease. Incidence rates of post-op VTE, hemorrhage (Hge) and infection (Inf) were calculated and compared between patients with bleeding disorders and those without bleeding disorders regardless of pharmacologic ThPPx. The same outcomes were obtained and compared between patients with/without bleeding disorders who received ThPPx. Chi-square and Fischer exact test were used to determine statistical significance. Results: 333,584 patients underwent HA or KA. Out of these, 438 patients had bleeding disorder. The incidence rates of post-op VTE were 0.01% in patients with bleeding disorders vs 0.02% in those without (p=0.1850) regardless of ThPPx which was not statistically significant. The incidence rate of post-op Hge was higher in patients with bleeding disorders (0.01%) compared to patients without bleeding disorder (0.004%; p=0.0404). The difference in incidence rate of Inf was not statistically significant between the two groups (p=0.1768). Out of total patients, 202,936 patients who underwent KA or HA received ThPPx. The difference in incidence rates of VTE as well as Inf were not statistically significant between patients with and without bleeding disorders who received ThPPx (p=0.2357 for VTE and p=0.2519 for Inf). The incidence rate of post-op Hge in patients who received ThPPX and had bleeding disorder was 0.014% in contrast to 0.004% in patients without bleeding disorder, though, it did not reach statistical significance (p=0.0684). Conclusion: Patients with bleeding disorders have a similar risk of post-op VTE as the general population after HA or KA. Patients with bleeding disorders have higher post-op hemorrhagic complications. However, when comparing only those patients who received ThPPx, the difference in incidence of post-op Hge was not statistically significant. This implies that all patients including the ones with bleeding disorders, undergoing HA or KA may be treated with a similar ThPPx approach. Patients with bleeding disorders undergoing HA or KA do not have a higher predisposition to infections compared to the general population and may not require additional infection control measures. We did not look at the differences in factor treatment perioperatively which would have been standard for all bleeding disorder patients if they followed in a hemophilia treatment center. Our study limitation was its retrospective nature as well as all HA, KA, post-op VTE, Hge and Inf were identified by CPT and ICD codes.

A Rare Cause of Recurrent Pain in Athletes: Synovial Hemangioma

Background: Synovial hemangioma is a rare neoplastic lesion, which can result in recurrent hemarthrosis and pain. It can affect any joint, tendon, or bursa, withal those around the knee. The intra-articular lesion is more prevalent and is more frequently diagnosed in female children or young adults. Indications: Surgery is indicated when patients present with recurrent painful hemarthrosis that affect daily living and functionality. Technique Description: Diagnostic knee arthroscopy, initially without tourniquet inflation, was performed to detect and study the extent of the lesion. Afterwards, the tourniquet was inflated to proceed with the surgical excision. Medial parapatellar approach was performed, and limits of the hemangioma were identified. Wide resection was performed taking care to not damage the medial meniscus and medial condyle cartilage. Neoplastic lesion was sent to pathology analysis. The tourniquet was deflated and hemostasis checked because these lesions can present extensive bleeding. Results: Localized, well-circumscribed, and encapsulated lesions have been reported to usually present low recurrence rate when completely excised. Discussion/Conclusion: It is a rare disease, and around 200 cases have been reported; therefore, conclusions about treatment and outcomes rely mostly on case series and case reports. Early diagnosis and treatment are paramount to prevent degenerative changes secondary to recurrent hemarthrosis. Patient Consent Disclosure Statement: The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication.

Mobilization under anaesthesia for correction of knee flexion deformity in haemophilia.

Haemophilia patients not treated with primary or secondary prophylaxis, often present with recurrent haemarthrosis. Knee is the most frequently involved joint leading to disabling knee flexion deformity (KFD). Here, we present a retrospective study of our experience on the role of mobilization under general anaesthesia in the correction of KFD. To study the effectiveness of mobilization under anaesthesia (MUA) for correction of knee flexion deformity (KFD) in persons with haemophilia (PWH). Outcome of all patients managed with MUA in our multidisciplinary haemophilia clinic from 2008 to 2019 were included for analysis. PWH with KFD>20 degree who underwent MUA were included in the study. Under general anaesthesia and cover of clotting factor replacement, gentle joint mobilization was done to achieve maximal correction in flexion deformity, followed by above knee casting in this position. The outcome measures assessed were reduction in knee flexion deformity following MUA and complications, if any. Thirty patients (34 knees) with knee flexion deformity were included in the study. Mean age of the study population was 14.23 years ± 8.3. Study population was analysed in two groups, Group 1 included patients who underwent single MUA and Group 2, patients who underwent two or more MUA. There was significant improvement in KFD correction in both groups. [Group 1; Mean difference: 22 ± 13.7, p value -0.01, 95% CI (16.4-27.5) and Group 2; Mean difference 48.8 ± 19.8, p value -0.00, 95% CI (34.2-64.5)]. MUA can be effective in the short-term correction of KFD in PWH particularly those below 15 years of age. It should be done judiciously when target correction is not achieved with other physical methods.

Evaluation of collagen turnover biomarkers as an objective measure for efficacy of treatment with rurioctocog alfa pegol in patients with hemophilia A: a secondary analysis of a randomized controlled trial

BackgroundPatients with hemophilia who have recurrent hemarthroses develop hemophilic arthropathy (HA). Regular prophylaxis with factor (F) VIII (FVIII) can reduce HA, but there is a need for objective outcome measures to evaluate treatment efficacy. ObjectivesEvaluate and assess collagen turnover biomarkers in patients with hemophilia A to determine the efficacy of rurioctocog alfa pegol treatment and understand their potential as tools for guiding treatment decisions and monitoring outcomes. MethodsJoint remodeling was assessed by analyzing serum levels of collagen remodeling products at baseline and months 3, 6, 9, and 12 in a 98 patient subset receiving pharmacokinetics-guided prophylaxis with rurioctocog alfa pegol, targeting FVIII trough levels of 1 to 3 International Units (IU)/dL or 8 to 12 IU/dL (PROPEL study, NCT0285960). ResultsBasement membrane metabolism-related type 4 collagen remodeling products (C4M and PRO-C4) decreased after 3 months at all time points by up to 25% at 1 to 3 IU/dL (P = .049, P < .0001) and 8 to 12 IU/dL FVIII trough levels (P = .0002, P < .0001). Interstitial tissue metabolism-related type 3 (C3M) and 5 (PRO-C5) collagen remodeling products decreased after 3 months, by up to 19% at 1 to 3 IU/dL FVIII trough level (P = .0001, P = .009) and 23% at 8 to 12 IU/dL FVIII trough level (P = .0002, P = .001). An increase of up to 12% was seen for cartilage metabolism-related type 2 collagen product (PRO-C2, not C2M) after 6 months at both trough levels (P = .01, P = .005). When stratified by prior treatment, changes in C3M (P = .03) and C4M (P = .02) levels were observed between trough levels for prior on-demand treatment but not for prophylaxis prior to study entry. ConclusionJoint improvement measured by collagen remodeling biomarkers specific to the basement membrane, interstitial matrix, and cartilage was seen with pharmacokinetics-guided prophylaxis. These collagen remodeling biomarkers warrant further exploration as biomarkers to guide treatment toward improvement in HA.

T2 mapping magnetic resonance imaging of cartilage in hemophilia

BackgroundIn hemophilia, recurrent hemarthrosis may lead to irreversible arthropathy. T2 mapping MRI may reflect cartilage changes at an earlier reversible stage of arthropathy as opposed to structural MRI. ObjectivesTo evaluate interval changes of T2 mapping compared with the International Prophylaxis Study Group (IPSG) structural MRI scores of ankle cartilage in boys with hemophilia receiving prophylaxis. MethodsEight boys with hemophilia A (median age, 13; range, 9-17 years), 7 age- and sex-matched healthy boys (controls, median age, 15; range, 7-16 years). A multiecho spin-echo T2-weighted MRI sequence at 3.0T was used to obtain T2 maps of cartilage of boys with hemophilia and controls. Structural joint status was evaluated using the IPSG MRI score. ResultsT2 relaxation times of ankle cartilage increased significantly over time in both persons with hemophilia and controls (P = .002 and P = .00009, respectively). Changes in T2 relaxation time strongly correlated with changes in IPSG cartilage scores (rs = 0.93 to rs = 0.78 [P = .0007 to P = .023]), but not with changes in age (P = .304 to P = .840). Responsiveness of T2 relaxation times were higher than that of IPSG cartilage scores, with standardized response means >1.4 for T2 mapping in all regions-of-interest compared with 0.84 for IPSG cartilage scores. Baseline T2 relaxation time strongly correlated with timepoint 2 IPSG cartilage score (rs = 0.93 to rs = 0.82 [P = .001 to P = .012]) and T2 relaxation time (rs = 0.98 to rs = 0.88 [P = .00003 to P = .004]) changes in most regions-of-interest. ConclusionT2 mapping shows sensitivity to biochemical changes in cartilage prior to detectable damage using conventional MRI, offering potential for early detection of bleed-related cartilage damage in boys with hemophilia.

Mesenchymal Stromal Cells Prevent Blood-induced Degeneration of Chondrocytes in a New Model of Murine Hemarthrosis

Hemophilia is a rare congenital bleeding disorder caused by deficiency in coagulation factors VIII or IX, which is treated with prophylactic clotting factor concentrates. Nevertheless despite prophylaxis, spontaneous joint bleedings or hemarthroses still occur. The recurrent hemarthroses lead to progressive degradation of the joints and severe hemophilic arthropathy (HA) in patients with moderate and even mild forms of the disease. In absence of disease modifying treatment to stop or even delay HA progression, we aimed at evaluating the therapeutic potential of mesenchymal stromal cells (MSCs)-based therapy. We first developed a relevant and reproducible in vitro model of hemarthrosis relying on blood exposure of primary murine chondrocytes. We found that 30% whole blood for 4 days allowed to induce the characteristic features of hemarthrosis including low survival of chondrocytes, apoptosis induction, and dysregulation of chondrocyte markers in favor of a catabolic and inflammatory phenotype. We then evaluated the potential therapeutic effects of MSCs in this model using different conditions of coculture. Addition of MSCs improved the survival of chondrocytes when added either during the resolution or the acute phases of hemarthrosis and exerted a chondroprotective effect by enhancing the expression of anabolic markers, and reducing the expression of catabolic and inflammatory markers. We here provide the first proof-of-concept that MSCs may exert a therapeutic effect on chondrocytes under hemarthrosis conditions using a relevant in vitro model, thereby confirming a potential therapeutic interest for patients with recurrent joint bleedings.

Orthopedic surgical procedures in people with hemophilia.

People with hemophilia tend to develop joint lesions secondary to the recurrent hemarthroses typical of their condition. These usually include chronic synovitis and arthropathy chiefly affecting their ankles, knees, and elbows. In addition, muscular hematomas, albeit less frequently, may also result in complications such as acute compartment syndrome, pseudotumors, bone cysts and peripheral nerve compression. Joint lesions may require some of the following surgical interventions: arthroscopic synovectomy (in cases of synovitis), arthroscopic joint debridement, radial head resection, opening-wedge tibial osteotomy, arthrodesis, arthrodiastasis (of the ankle), tendon lengthening (hamstrings, Achilles tendon), progressive extension of the knee by placing an external fixator in cases of flexion contracture of the knee, supracondylar femoral extension osteotomy in cases of knee flexion contracture and, eventually, a total joint arthroplasty when the affected joint has been destroyed and the patient experiences severe joint pain. Total knee arthroplasty in hemophilic patients is associated with a high infection risk (7% on average). As regards the complications following muscle hematomas, acute compartment syndrome requires urgent performance of a fasciotomy when hematological treatment is incapable of resolving the problem. Surgical resection of hemophilic pseudotumors is the best solution, with those affecting the pelvis (secondary to iliopsoas hematomas) being particularly difficult to resolve. Peripheral nerve lesions can often be effectively addressed with hematological treatment, although a surgical neurolysis of the ulnar nerve is indicated if nonoperative treatment fails.

Hemophilic Arthropathy of the Knee and Its Association with Reduced Muscle Strength and Activation and the Pressure Pain Threshold: A Case-Control Study.

(1) Background: Hemophilia is characterized by recurrent hemarthrosis leading to degenerative arthropathy. The aim was to evaluate the differences in muscle strength and activity and the pressure pain threshold between patients with knee arthropathy and their healthy peers; (2) Methods: A case-control study in which 23 adult patients with knee arthropathy and 24 healthy peers matched in terms of characteristics were recruited. The study variables were quadriceps muscle strength, muscle activation and the pressure pain threshold; (3) Results: There were significant differences between the two groups in quadriceps strength on the dominant (CI95%: 64.69, 129.2) and non-dominant (CI95%: 29.95, 93.55) sides and in the pressure pain threshold on the dominant (CI95%: 3.30, 43.54) and non-dominant (CI95%: 3.09, 45.25) sides. There were differences in neuromuscular fatigue on the non-dominant side in the vastus medialis (CI95%: 8.72, 21.51), vastus lateralis (CI95%: 4.84, 21.66) and rectus femoris (CI95%: 6.48, 24.95) muscles; (4) Conclusions: Muscle strength and the pressure pain threshold are lower in patients with hemophilia. Quadriceps muscle activation in patients with hemophilic knee arthropathy does not in any way differ from activation in healthy subjects. However, muscle fatigue is greater in patients with knee arthropathy. Strength training in patients with hemophilia should focus on the activation of the vastus medialis and lateralis muscles.

What is the Effect of Bevacizumab on Cartilage and Synovium in a Rabbit Model of Hemophilic Arthropathy?

Hemophilic arthropathy can cause recurrent hemarthroses and severe damage to the synovium and articular cartilage. Previous studies have shown that vascular endothelial growth factor (VEGF) plays an essential role in neoangiogenesis. Bevacizumab, a monoclonal VEGF inhibitor, is used clinically to prevent angiogenesis. However, its effects on hemophilic arthropathy are unknown. Using a hemophilic arthropathy rabbit model, we asked: Does an intra-articular injection of bevacizumab (1) inhibit VEGF, (2) decrease signal intensity in dynamic contrast-enhanced MRI (DCE-MRI) as an assessment of capillary permeability and neoangiogenesis, (3) reduce cartilage damage, (4) reduce synovial changes, and (5) affect macroscopic changes during the development of hemophilic arthropathy? Twenty-five male New Zealand rabbits were divided into four groups. Eight knees from four rabbits were used as the control group. We used an established animal model for hemophilic arthropathy in the remaining 21 rabbits. Animals were assigned randomly to three groups with seven rabbits in each group. One group was used to establish mild arthropathy, and the other two were used to establish severe arthropathy. Autologous blood from the rabbits' ears was injected into the right and left knees twice per week for 8 weeks to represent mild arthropathy and for 16 weeks to represent severe arthropathy. In the mild arthropathy group, bevacizumab was injected into the right knee once every 2 weeks. Bevacizumab was injected into the right knee of rabbits in one of the severe arthropathy groups once every 2 weeks for 16 weeks, and intra-articular bevacizumab injections were administered to the right knees of rabbits in the other severe arthropathy group once every 2 weeks after the eighth week. An equal volume of 0.9% saline was injected into the left knee of rabbits in all arthropathy groups. To explore the efficacy of bevacizumab, joint diameters were quantitatively measured, and cartilage and synovial changes were examined. Degeneration of articular cartilage was evaluated with the semiquantitative Osteoarthritis Research Society International grading system. Synovial damage was analyzed with a semiquantitative microscopic scoring system. In addition, we evaluated perfusion and angiogenesis using DCE-MRI (quantitative signal intensity changes). Immunohistochemical testing was used to measure VEGF levels (analyzed by Western blotting). Intra-articular bevacizumab treatment inhibited VEGF in our rabbit model of hemophilic arthropathy. VEGF protein expression levels were lower in the mild arthropathy group that received intra-articular bevacizumab (0.89 ± 0.45) than the mild arthropathy control group (1.41 ± 0.61) (mean difference -0.52 [95% CI -0.898 to -0.143]; p = 0.02). VEGF levels were lower in the severe arthropathy group that received treatment for 16 weeks (0.94 ± 0.27) than in the control knees (1.49 ± 0.36) (mean difference -0.55 [95% CI -0.935 to -0.161]; p = 0.01). In the severe arthropathy group, the Osteoarthritis Research Society International score indicating cartilage damage was lower in the group that received intra-articular bevacizumab treatment from the beginning than in the control group (median 17 [range 13 to 18] versus 18 [range 17 to 20]; difference of medians 1; p = 0.02). Additionally, the scores indicated synovial damage was lower in the group that received intra-articular bevacizumab treatment from the beginning than the control group (median 5 [range 4 to 9] versus 9 [range 8 to 12]; difference of medians 4; p = 0.02). The mean of mean values for signal intensity changes was higher in the nontreated severe groups than in the group of healthy knees. The signal intensity changes were higher in the severe arthropathy control groups (Groups BC and CC) (median 311.6 [range 301.4 to 361.2] and 315.1 [range 269.7 to 460.4]) than in the mild arthropathy control group (Group AC) (median 234.1 [range 212.5 to 304.2]; difference of medians 77.5 and 81, respectively; p = 0.02 and p = 0.04, respectively). In the severe arthropathy group, discoloration caused by hemosiderin deposition in the cartilage and synovium was more pronounced than in the mild arthropathy group. In the severe arthropathy group treated with intra-articular bevacizumab, joint diameters were smaller than in the control group (Group BT median 12.7 mm [range 12.3 to 14.0] versus Group BC median 14.0 mm [range 13.1 to 14.5]; difference of medians 1.3 mm; p = 0.02). Hemarthrosis damages the synovial tissues and cartilage in the knees of rabbits, regardless of whether they are treated with intra-articular bevacizumab. However, intra-articular injection of bevacizumab may reduce cartilage and synovial damage in rabbits when treatment is initiated early during the development of hemophilic arthropathy. If the findings in this study are replicated in larger-animal models that consider the limitations of our work, then a trial in humans might be appropriate to ascertain whether intra-articular injection of bevacizumab could reduce cartilage damage and synovial changes in patients with hemophilia whose hemarthroses cannot otherwise be controlled.

Geniculate Artery Endovascular Embolization Post-Total Knee Arthroplasty for Hemarthrosis Treatment: A Systematic Review of the Literature

Purpose: To provide an updated systematic review on the use of geniculate artery embolization (GAE) in the management of recurrent hemarthrosis post-total knee arthroplasty (TKA). Materials and Methods: A systematic literature review was conducted, and all clinical reports in the English language from inception to July 2022 were identified. References were manually reviewed to identify additional studies. Demographics, procedural techniques, post-procedural complications, and follow-up data were extracted and analyzed using STATA 14.1. Results: A total of 20 studies (9 case reports, 11 case series; n= 214) were included for review. In all cases, patients underwent coil embolization of one or more geniculate arteries. Procedure success was reported in 94.8% (n=203/214) of cases without perioperative adverse events. Improvement of symptoms was seen in 72.6% (n=119/164) of cases, with 30.7% (n=58/189) of cases requiring repeat embolization. Recurrent hemarthrosis occurred in 22.2% (n=22/99) of cases over a mean follow-up of 48 months. Conclusion: GAE appears to be a safe and effective treatment for recurrent hemarthrosis following TKA. Future studies in the form of randomized controlled trials should be conducted to further evaluate such embolization techniques and compare outcomes between GAE and standard techniques. Clinical Impact Conservative management of post total knee arthroplasty (TKA) hemarthrosis is successful in only one third of cases. Geniculate artery embolization (GAE) has recently gained attention due to its minimally invasive nature compared to open or arthroscopic synovectomy promising faster rehabilitation, decreased infection rates and less additional surgeries. The purpose of this article was to summarize current literature, provide an updated review on the use of GAE in the management of recurrent hemarthrosis post-TKA and describe immediate and long-term outcomes in an effort to help optimize current treatment algorithms.

Artritis séptica de rodilla por Serratia marcescens en paciente con hemofilia A

We present the case of a 24-year-old male patient with hemophilia A of 14 years of evolution. The patient presented recurrent hemarthrosis in the right knee, who developed septic arthritis in knee due to Serratia marcescens with a satisfactory response to intra-articular lavage with saline solution and 28 days of treatment whith carbapenems. In patients with septic arthritis, previous hemarthrosis and multiple hospital admissions, the presence of this germ should be suspected. The treatment is surgical and with broad-spectrum antibiotics.