Chronic hemophilic synovitis (CHS), driven by hemosiderin-laden macrophages from recurrent hemarthrosis, is a major cause of joint damage in hemophilia. Platelet-rich plasma (PRP) is a promising regenerative therapy for joint diseases. This study investigated PRP’s ability to modulate macrophage polarization from a pro-inflammatory (M1) to a pro-resolving, tissue-repairing (M2) phenotype in CHS. We analyzed synovial fluid (SF) from CHS patients (N = 22), both pre- and post-PRP treatment. Ex vivo analysis revealed a predominant M1 profile with an increased proportion of CD11+CD14+CD64hi compared with CD206+ or CD163+ M2 macrophages in CHS SF. In vitro experiments showed that CHS SF skewed monocyte-derived macrophages toward an M1 inflammatory program, evaluated by flow cytometry, qPCR, and ELISA. However, adding PRP significantly modulated the pro-inflammatory macrophage program, promoting an M2 tissue repair profile. Furthermore, a random forest machine learning algorithm, applied to public scRNAseq data, confirmed PRP’s macrophage reprogramming effect. Functional assays also showed increased TGF-β secretion and macrophage fusion when challenged with neutrophil extracellular traps (NETs). A small patient follow-up cohort treated with intra-articular PRP showed similar results, including normalization of cellular content and reduced CD64/CD206 expression. These findings indicate that PRP treatment effectively shifts SF-associated M1 macrophages to an M2-like phenotype, highlighting its potential as a therapeutic strategy for CHS.

Intra-articular blood, iron and hemosiderin, hydroxyl radical cytokines, and neo-angiogenesis cause synovial inflammation, which leads to cartilage and joint damage. Platelet-rich plasma (PRP) inhibits most of the mediators that produce and maintain synovitis. We compile here our work showing the clinical effectiveness of intra-articular PRP injections and their potential role in stopping articular cartilage damage due to bleeding and its possible repair. A total of 116 joints, including knees (63%), elbows (19.8%), and ankles (17.2%), were treated with intra-articular injections of PRP. Moreover, we also show here the number of extracellular DNA traps (ETs) and the PRP effect in the synovial fluid of patients at the time of treatment and six months after. Clinically, it is demonstrated that PRP is effective in reducing bleeding episodes (p < 0.001) and pain (p < 0.0001) and improving the hemophilia joint health score (HJHS) (p < 0.001) at one year of follow-up. Furthermore, our results demonstrate that PRP inhibits ET formation in vitro and reconstitutes the immune system’s cellular components in the synovial fluid of patients after treatment. We conclude that PRP can be considered an effective, safe, and easy treatment for hemophilic synovitis.

INTRODUCTION:The impact of joint damage on functional capacity in patients with mild haemophilia (PwMH) has yet to be well studied. The primary aim of this study was to investigate the effect of joint impairment on the functional capacity of the lower limb in PwMH. The secondary aim was to identify physical predictors of lower limb functional capacity.METHOD:Forty-nine PwMH were evaluated. Dynamic balance was assessed using Time Up and Go (TUG). Thirty-second sit-to-stand (30-STS) and 60-second-STS (60-STS) were used to assess muscle power and endurance, respectively. Haemophilia Early Arthropathy Detection with Ultrasound (HEAD-US) was used to assess joint damage. PwMH were divided based on HEAD-US: with joint damage (≥3 points) and without or with very low joint damage (0-2 points). Univariate ANOVA and multiple regression analyses were performed to identify differences in functional capacity and potential physical predictors.RESULTS:Only 30-STS showed significant differences between groups (p = .002). TUG and 60-STS were primarily explained by age (r2  = .21 and r2  = .44, respectively), while for 30-STS, age combined with joint damage and pain level explains 54% of the variance.CONCLUSION:Our findings indicate that the 30-STS is useful for assessing functional deterioration in people with early-stage haemophilia-related arthropathy. Our results also indicate that joint damage, combined with ageing and pain, may impact 30-STS outcomes in PwMH. Furthermore, our findings show that the loss in TUG and 60-STS performance in PwMH is related to ageing.

IntroductionPeople with mild haemophilia (PWMH) experience sporadic bleeds and are less likely to receive an early diagnosis, appropriate treatment and medical care. Arthropathy is a key determinant of health-related quality of life (QoL), producing pain, limitations in mobility and daily activities. The aim of this study is to evaluate the incidence, risk factors and QoL associated with arthropathy in PWMH. Materials and MethodsObservational, cross-sectional cohort study. Data were collected in a single interview and evaluated by a physiotherapist and an orthopaedist and analysed on demographics; baseline factor levels; as well as clinical (Haemophilia Joint Health Score [HJHS]), ultrasound (Haemophilia Early Arthropathy Detection with Ultrasound [HEAD-US]), radiological (Pettersson score [PS]), pain (visual analogue scale [VAS]) and QoL evaluations. We defined arthropathy when at least one of the joints shown with a HEAD-US score >= 1. ResultsEighty-five patients and 510 joints were included. Patients' mean age was 35.9 years-old. Median age was 44.2 in patients with arthropathy versus 14.9 in patients without; the difference was statistically significant (p < .001). In patients over 20 years old, 90.5% shown arthropathy. Only 24 (28%) patients had no joint damage (HEAD-US = 0), and 61 (72%) had at least one joint with a HEAD-US >= 1. The ankle was the most affected joint. Patient age was found to be the most important risk factor associated with the development of arthropathy. ConclusionsJoint damage as a result of prior hemarthrosis was the most relevant factor associated with lower QoL, and emphasised the importance of early diagnosis and appropriate management in this particular population.

Prophylaxis is the gold standard treatment for children with haemophilia (CWH). MRI studies revealed joint damage, even with this treatment; this suggests the presence of subclinical bleeding.In the case of children with haemophilia, it is relevant to detect early signs of joint damage, as this allows the medical team to provide the appropriate treatment and follow-up, in order to avoid arthropathy development and its consequences. The aim of this study is to detect the hidden joint in children with haemophilia on prophylaxis (CWHP) and analyse, by age group, which joint is the most affected. We define the hidden joint in CWH on prophylaxis as the joint that presents joint damage secondary to repetitive bleeding episodes and is detected in the joint evaluation, despite being asymptomatic or with mild symptoms. It is most commonly caused by repetitive subclinical bleeding.Methods: This was an observational, analytical, cross-sectional study of 106 CWH on prophylaxis treated in our centre. Patients were divided according to age and type of treatment. Joint damage was defined as a HEAD-US score ≥1. Results: Patients’ median age was 12 years. All had severe haemophilia. The median age of onset of prophylaxis was 2.7. Forty-seven (44.3 %) patients received primary prophylaxis (PP) and 59 (55.7 %), secondary prophylaxis. Six hundred and thirty-six joints were analysed. Type of prophylaxis and joint involvement showed statistically significant differences (p<0.001). However, patients on PP had a greater number of damaged joints at older ages. Twenty- two percent (140) of the joints scored ≥ 1 on HEAD-US. Cartilage was most frequently involved, followed by synovitis, and bone damage. We observed a greater frequency and degree of arthropathy in subjects aged 11 and above. Sixty (12.7 %) joints showed a HEAD-US score ≥ 1, with no history of bleeding. The ankle was the most affected joint, representing the hidden joint according to our definition.Prophylaxis is the best treatment for CWH. However, symptomatic or subclinical joint bleeding may occur. The routine evaluation of joint health is relevant, particularly, of the ankle. In our study, early signs of arthropathy according to age and type of prophylaxis were detected by HEAD-US.

INTRODUCTION:Hemarthrosis causes chronic haemophilic synovitis (CHS). Although neutrophils are major immune cells infiltrating joints after bleeding, their role on the pathogenesis of CHS is unknown. Neutrophils release extracellular DNA traps (ETs), structures of DNA with bound granular enzymes that were associated with tissue damage.AIMS:To evaluate the presence of ETs as pathogenic biomarker and the protective effect of intraarticular injection of platelet-rich plasma (PRP) in patients with CHS.METHODS:Haemophilia Joint Health Score (HJHS) and bleeding episodes (BE) were measured and correlated with ETs indicators (DNA/DNA-Elastase) in synovial fluids (SF), PRP and plasma of 21 patients.RESULTS:Soluble DNA and DNA-Elastase were detected in SF and plasma of patients. The synovial and plasma levels of DNA-Elastase positively correlated with worse HJHS/BE. Interestingly, remaining ETs-inducer factors were present in SF that induced the in vitro release of ETs from blood-isolated neutrophils. This phenomenon was impaired by adding plasma or PRP. Finally, preliminary data obtained from five patients indicate that levels of DNA-Elastase and HJHS/BE decreased after receiving intraarticular injection of PRP.CONCLUSIONS:The synovial and plasma levels of DNA-Elastase correlated with worse HJHS/BE suggesting that ETs formation could be a biomarker and potential therapeutic target for CHS. The intraarticular injection of PRP underlined a new potential alternative therapy, decreasing ETs formation in synovia of patients with CHS. However, our hypotheses must be confirmed in the future with better designed and more statistical power studies. Meanwhile, the use of intraarticular injections of PRP for the treatment of CHS remains controversial.

Background: Platelet-rich plasma is an autologous blood product defined by a concentration of platelets higher than baseline. Enough evidence supports its application for the treatment of orthopedic disorders. Objectives: The aim of this study was to report the absence of infection and/or complication events related to platelet-rich plasma treatment in patients with musculoskeletal disorders of diverse etiologies. Methods: This transversal and descriptive study included a total of 513 patients, presenting either common orthopedic disorders or hemophilic synovitis/arthropathy. Peripheral whole blood was collected in the presence of anticoagulant and centrifuged. Platelet-rich fraction was separated under sterile conditions. Before injection, the affected area was sanitized and covered with sterile field drapes. Injections were performed in the procedure room under ultrasound image. No anesthesia or antibiotics were administered. Data were analyzed using Pearson’s chi-square test and Cramer’s V test. Results: Of the 923 procedures, 63.2% were intra-articular, and 36.8% were performed in soft tissues. Intra-articular injections were more common in patients with hemophilia, compared with patients without hemophilia (P < 0.001). The most commonly affected anatomical sites were: the knee, the ankle, the hip, and the elbow, with a higher prevalence of ankle and elbow disorders in patients with hemophilia, compared with patients without hemophilia (P < 0.001). Among patients with hemophilia, 13 presented HCV infection, one presented HIV infection, and three were coinfected with HCV and HIV. Twelve patients presented inhibitors. No complications were observed during blood extraction or after platelet-rich plasma injection. No infections occurred at the site of injection. Conclusions: Our platelet-rich plasma preparation and administration protocol under sterile conditions considerably reduce the chances of contamination and further complications associated with it. The occurrence of infection after intra-articular or soft tissue injection was nil in this study, even in patients with hemophilia.

Background: Inhibitor development is the main treatment-related complication in patients with hemophilia. Degenerative joint lesions caused by repeated bleeding episodes are more common in patients with inhibitors than in those without inhibitors. We introduced Platelet-rich Plasma (PRP) treatment to reduce joint damage and provide symptomatic relief. Objectives: The aim of this study was to compare PRP treatment outcomes in two groups of patients with hemophilia presenting synovitis, with or without inhibitors, at 3- and 6-month follow-ups. Methods: We treated 87 patients with 143 affected joints divided into two groups: 78 patients without inhibitors with 129 affected joints and a mean age of 25.8 years, and 9 patients with inhibitors with 14 affected joints and a mean age of 16.3 years. Results: The difference in mean age between the two groups was statistically significant (P=0.007). The number of bleeding episodes, Visual Analogue Scale (VAS), and Hemophilia Joint Health Score (HJHS) before treatment and after three and six months showed no statistically significant differences between groups. We demonstrated that PRP treatment decreased the number of bleeding episodes, pain levels, and HJHS in the whole study population (P<0.001). No differences were found between patients with and without inhibitors. Conclusion: PRP was proved to be effective for synovitis treatment in patients with hemophilia with and without inhibitors.

Repeated joint bleeding leads to chronic synovitis, cartilage damage and bone alterations which result in haemophilic arthropathy and are associated with pain, functional impairment and poor quality of life. There are evidence that Hyaluronic Acid (HA) and Platelet-rich Plasma (PRP) have different mechanisms of action in the treatment of arthropathy for this reason we decided to use both components. The aim of this study is to compare, the efficacy, safety and duration of a single intra-articular injection of PRP against PRP+HA for pain, bleeding episodes and joint health, in the same patient with bilateral hemophilic knee arthropathy. Twenty-one men patients (42 knee joints) were treated with intra- articular injections of PRP or PRP+HA. All of them were haemophilia type A severe. The mean age was 36.6 years (21-72). All patients were evaluated for: Haemophilia Joint Health Score (HJHS), pain (VAS), the number of bleeding episodes (BE) in the last 30 days, before treatment, at three and six months after treatment. Statistically significant improvement were shown for both knee joints at three and six months after treatment for VAS and BE (P < 0.00001). The HJHS score did not significantly improve for either knee in the 6-month period after injection. A single PRP or PRP+HA injection is safe and effective in treating haemophilic arthropathy of the knee for up to 6 months follow-up, reducing pain, bleeding episodes and delaying total knee arthroplasty.

Introduction Primary prophylaxis is the current gold standard in haemophilia care for the prevention of bleeding and ensuing joint damage. Early detection of joint bleeding, whether symptomatic or subclinical, preferably during childhood, helps prevent joint deterioration and subsequent disability. The aim of this study is to evaluate the level of agreement between the Haemophilia Joint Health Score and the Haemophilia Early Arthropathy Detection with Ultrasound tools in children with severe haemophilia on primary and secondary prophylaxis. Materials and Methods All patients were followed up regularly at our centre. Elbows, knees and ankles were evaluated by physical examination using the Haemophilia Joint Health Score 2.1 (HJHS 2.1), and by ultrasound with HEAD-US score. Results A total of 80 children with haemophilia on prophylaxis were included in this study. Mean age was 10.8 years (range 4-18). We evaluated 480 joints, of which 423 (88.1%) were concordant with both tools, whereas 57 (11.9%) were discordant; 377 (78.5%) joints scored 0 on HJHS, 370 (77%) on HEAD-US and 345 (72%) on both tools. The overall Kappa concordance coefficient was .656. For elbows, knees and ankles the respective values were .783, .522 and .589. For HJHS scores greater than 3, all joints scored >= 1 on HEAD-US. Conclusion HJHS and HEAD-US are used to assess joint health in children with haemophilia on prophylaxis. In this study, the level of agreement between both tools was consistent with literature values only for the elbow joint.

Introduction: Hemophilia is a coagulation disorder; it is a recessive disease linked to the X chromosome.In patients with hemophilia (PWH), regional anesthetic blocks have been considered a contraindication.Safety has been increased by performing them guided by Ultrasound.The objective of our work is to show our experience in PWH and peripheral nerve blocks.Material and Method: 41 PWH were operated under regional analgesia with Ultrasound-Guided Peripheral Nerve Blocks associated with general anesthesia in the period 2006-2019.All patients were Hemophilia A. Three patients had inhibitors.The mean age was 35 years.40 lower limb blocks and 2 upper limb blocks were performed.The Sonosite ® equipment model Micromaxx was used.Results: All patients presented adequate peripheral nerve block for an average time of 12.5 hours (8-24).There were no complications.Conclusion: The present study shows that Ultrasound-Guided Peripheral Nerve Blocks in PCH is a safe procedure, which reduces the requirements of opioids and the side effects of them, improving the postoperative period and the recovery of patients.