Tranexamic Acid Use in Knee and Shoulder Arthroscopy Leads to Improved Outcomes and Fewer Hemarthrosis-Related Complications: A Systematic Review of Level I and II Studies.

PURPOSE: To systematically review the literature to compare the efficacy and safety of tranexamic acid (TXA) as a means to minimize hemarthrosis-related complications after arthroscopic procedures of the knee, hip, and shoulder. METHODS: A systematic review according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was performed by searching PubMed, Cochrane Library, and Embase databases to locate randomized controlled trials comparing the clinical outcomes and postoperative complications of patients undergoing arthroscopy with and without TXA. Search terms used were "tranexamic acid," "arthroscopy," "knee," "hip," and "shoulder." Patients were evaluated based on early (<6 weeks) postoperative signs of hemarthrosis using the Coupens and Yates classification, postoperative complications (myocardial infarction, stroke, venous thromboembolism events), range of motion (ROM), and patient-reported outcome scores (Visual analog scale, Subjective International Knee Documentation Committee, Lysholm, and Tegner activity scores). RESULTS: Five studies (2 level I and 3 level II) met inclusion criteria, including a total of 299 patients undergoing arthroscopy with TXA and 299 patients without TXA. The average follow-up duration for all patients was 43.9 days. Procedures performed were partial meniscectomy, anterior cruciate ligament reconstruction, and rotator cuff repair. No studies evaluating TXA use in hip arthroscopy were identified. Coupens-Yates hemarthrosis grades significantly improved in the TXA groups across all studies. Three studies found TXA patients to experience significantly less postoperative pain at latest follow-up, 1 study found TXA patients to have significantly better postoperative Lysholm scores, and 1 study found TXA patients to have significantly more ROM at latest follow-up compared with non-TXA patients (P < .05). CONCLUSION: Patients undergoing arthroscopy, particularly arthroscopic meniscectomy, arthroscopic-assisted anterior cruciate ligament reconstruction, and arthroscopic rotator cuff repair, with TXA can be expected to experience improved outcomes and less hemarthrosis-related complications in the early postoperative period compared with non-TXA patients. LEVEL OF EVIDENCE: II, systematic review of level I and II studies.

Blood in the joint: effects of hemarthrosis on meniscus health and repair techniques.

Injury to the meniscus is common and frequently leads to the development of post-traumatic osteoarthritis (PTOA). Many times meniscus injuries occur coincident with anterior cruciate ligament (ACL) injuries and lead to a bloody joint effusion. Hemarthrosis, or bleeding into the joint, has been implicated in degeneration of joint tissues. The goal of this review paper is to understand the pathophysiology of blood-induced joint damage, the possible effects of blood on meniscus tissue, and the implications for current meniscus repair techniques that involve the introduction of blood-derived products into the joint. In this review, we illustrate the similarities in the pathophysiology of joint damage due to hemophilic arthropathy (HA) and osteoarthritis (OA). Although numerous studies have revealed the harmful effects of blood on cartilage and synovium, there is currently a gap in knowledge regarding the effects of hemarthrosis on meniscus tissue homeostasis, healing, and the development of PTOA following meniscus injury. Given that many meniscus repair techniques utilize blood-derived and marrow-derived products, it is essential to understand the effects of these factors on meniscus tissue and the whole joint organ to develop improved strategies to promote meniscus tissue repair and prevent PTOA development.

EPCR deficiency or function-blocking antibody protects against joint bleeding-induced pathology in hemophilia mice.

We recently showed that clotting factor VIIa (FVIIa) binding to endothelial cell protein C receptor (EPCR) induces anti-inflammatory signaling and protects vascular barrier integrity. Inflammation and vascular permeability are thought to be major contributors to the development of hemophilic arthropathy following hemarthrosis. The present study was designed to investigate the potential influence of FVIIa interaction with EPCR in the pathogenesis of hemophilic arthropathy and its treatment with recombinant FVIIa (rFVIIa). For this, we first generated hemophilia A (FVIII-/-) mice lacking EPCR (EPCR-/-FVIII-/-) or overexpressing EPCR (EPCR++ FVIII-/-). Joint bleeding was induced in FVIII-/-, EPCR-/-FVIII-/-, and EPCR++FVIII-/- mice by needle puncture injury. Hemophilic synovitis was evaluated by monitoring joint bleeding, change in joint diameter, and histopathological analysis of joint tissue sections. EPCR deficiency in FVIII-/- mice significantly reduced the severity of hemophilic synovitis. EPCR deficiency attenuated the elaboration of interleukin-6, infiltration of macrophages, and neoangiogenesis in the synovium following hemarthrosis. A single dose of rFVIIa was sufficient to fully prevent the development of milder hemophilic synovitis in EPCR-/-FVIII-/- mice. The development of hemophilic arthropathy in EPCR-overexpressing FVIII-/- mice did not significantly differ from that of FVIII-/- mice, and 3 doses of rFVIIa partly protected against hemophilic synovitis in these mice. Consistent with the data that EPCR deficiency protects against developing hemophilic arthropathy, administration of a single dose of EPCR-blocking monoclonal antibodies markedly reduced hemophilic synovitis in FVIII-/- mice subjected to joint bleeding. The present data indicate that EPCR could be an attractive new target to prevent joint damage in hemophilia patients.

Magnetic Resonance Imaging of Hemophilic Joints: Correlations with the Bleeding Phenotype and Physical Examination.

INTRODUCTION: Blood-induced joint damage as a hallmark of haemophilia continues to occur despite the widespread prophylaxis. Pre-cise assessment and follow-up of joint status are crucial for tailoring their treatment. AIM: To study the correlation between the bleeding phenotype, the functional joint status, and the magnetic resonance imaging score in pediatric patients with haemophilia. MATERIALS AND METHODS: Eighty-six joints (ankles, knees, and elbows) in patients aged 10.7±0.5 (range 4 - 20) years with severe/moderate haemophilia A, severe haemophilia B and haemophilia A with inhibitors were included in the study. The joints were assessed by Haemophilia Joint Health Score 2.1 (HJHS2.1) one month after the last hemarthrosis in a non-bleeding state. The magnetic reso-nance imaging was performed on 40 (46.5%) of the examined hemophilic joints (16 ankles, 11 knees and 13 elbows). RESULTS: Joint bleeds were present in 37 (38.9%) of the joints with ankles being the most commonly affected. Sixty joints (69.8%) had normal HJHS2.1 score. Only the loss of flexion score differed significantly between the joints and the ankles had highest score. The cumulative number of hemarthrosis in the joint correlated moderately with hemosiderin deposition and strongly with the formation of subchondral cysts on magnetic resonance imaging. The magnetic resonance imaging scores for soft tissue and osteochondral domains correlated moderately with the cumulative number of hemarthrosis in the joint and only with the presence of pain and crepitus of mo-tion from the physical examination. CONCLUSIONS: Magnetic resonance imaging is more sensitive than the bleeding phenotype and physical examination in detecting early signs of haemophilic arthropathy.

[Radionuclide synoviorthesis in hemophilia: experience in 107 patients]. / Sinoviortesis con radioisótopos en hemofilia: Experiencia de un centro en Chile.

BACKGROUND: In patients with hemophilia, radionuclide synoviorthesis, or the intra-articular injection of a radionuclide to decrease the synovial hypertrophy tissue, aims to decrease or avoid hemarthrosis. AIM: To evaluate the effectiveness of radionuclide synoviorthesis in hemophilia. MATERIAL AND METHODS: Observational retrospective study of the evolution of 107 male patients aged 3 to 54 years who were subjected to radionuclide synoviorthesis between 2007 and 2015. RESULTS: Of 164 treated joints, in 65% treatment was successful, (defined as zero to two hemarthroses and absence of synovitis during the follow up period), in 17% it was partially successful (defined as two or less hemarthroses, but persistence of the synovitis) and failed in 18% of the procedures. No important complications were recorded. CONCLUSIONS: Radionuclide synoviorthesis has an overall 82% success rate, is minimally invasive, can be used at any age and is inexpensive We recommend its implementation in Chilean hemophilia treatment centers.

Mechanisms of vascular permeability and remodeling associated with hemarthrosis in factor VIII-deficient mice.

BACKGROUND: Vascular remodeling associated with hemophilic arthropathy (HA) may contribute to bleed propagation, but the mechanisms remain poorly understood. OBJECTIVES: To explore molecular mechanisms of HA and the effects of hemostasis correction on synovial vascular remodeling after joint injury in hypocoagulable mice. METHODS: Factor VIII (FVIII)-deficient mice +/- FVIII treatment and hypocoagulable wild-type mice (Hypo BALB/c) were subjected to subpatellar puncture. Hypo BALB/c mice were treated with warfarin and anti-FVIII before injury, after which warfarin was continued for 2 weeks or reversed +/- continuous anti-FVIII until harvest. Synovial vascularity was analyzed at baseline and 2 to 4 weeks post injury by histology, musculoskeletal ultrasound with power Doppler (microvascular flow), and Evans blue extravasation (vascular permeability). Synovial gene expression and systemic markers of vascular collagen turnover were studied in FVIII-deficient mice by RNA sequencing and enzyme-linked immunosorbent assay. RESULTS: Vascular changes occurred in FVIII-deficient and Hypo BALB/c mice after injury with minimal effect of hemostasis correction. Increased vascular permeability was only significant in FVIII-deficient mice, who exhibited more pronounced vascular remodeling than Hypo BALB/c mice despite similar bleed volumes. FVIII-deficient mice exhibited a strong transcriptional response in synovium that was only partially affected by FVIII treatment and involved genes relating to angiogenesis and extracellular matrix remodeling, with vascular collagen turnover markers detected systemically. CONCLUSIONS: Intact hemostasis at the time of hemarthrosis and during healing are both critical to prevent vascular remodeling, which appears worse with severe and prolonged FVIII deficiency. Unbiased RNA sequencing revealed potential targets for intervention and biomarker development to improve management of HA.

Sinoviortesis con radioisótopos en hemofilia: Experiencia de un centro en Chile / Radionuclide synoviorthesis in hemophilia: experience in 107 patients

Background: In patients with hemophilia, radionuclide synoviorthesis, or the intra-articular injection of a radionuclide to decrease the synovial hypertrophy tissue, aims to decrease or avoid hemarthrosis. Aim: To evaluate the effectiveness of radionuclide synoviorthesis in hemophilia. Material and Methods: Observational retrospective study of the evolution of 107 male patients aged 3 to 54 years who were subjected to radionuclide synoviorthesis between 2007 and 2015. Results: Of 164 treated joints, in 65% treatment was successful, (defined as zero to two hemarthroses and absence of synovitis during the follow up period), in 17% it was partially successful (defined as two or less hemarthroses, but persistence of the synovitis) and failed in 18% of the procedures. No important complications were recorded. Conclusions: Radionuclide synoviorthesis has an overall 82% success rate, is minimally invasive, can be used at any age and is inexpensive We recommend its implementation in Chilean hemophilia treatment centers.

Assessment of Kinect V2 for elbow range of motion estimation in people with haemophilia using an angle correction model.

INTRODUCTION: The joint range of motion (ROM) is an important clinical parameter used to assess the loss of functionality resulting from joint bleedings in people with haemophilia. These episodes require a close follow-up and, to decrease patients' hospital dependence, telemedicine tools are needed. Therefore, this study is aimed to analyse the validity of the Microsoft Kinect V2 sensor with corrected angle measurement to be used in the monitoring of elbow ROM in people with haemophilia. METHODS: A convenience sample of 10 healthy controls (CG) and 10 patients with haemophilia with elbow arthropathy (HG) participated in this study. Full ROM of elbow joints was measured in the frontal view with a 10-degree sweep using: (a) a clinical goniometer; (b) the Kinect V2; (c) the Kinect V2 with angle correction; and (d) using a photograph. Bland-Altman graphs (mean and 95% Limits of Agreement [LOA]) and Wilcoxon test were used to determine differences between measurements and groups. RESULTS: The angle-corrected Kinect V2 measurement removed the skew in the original data, reducing the average errors from 7.9° (LoA = -10.3°; 26.0°; CG) and 9.5° (LoA = -7.9°; 26.9°; HG) to -0.1° (LoA = -8.1°; 7.9°; CG) and -0.7° (LoA = -10.7°; 9.3°; HG). CONCLUSIONS: These error levels allow the use of Kinect V2 in the clinical practice. Kinect V2 with angle correction can complement the classical goniometry allowing an efficient and touchless measurement of ROM.

Anterior osteophyte resection of the ankle joint to increase range of motion in haemophilic ankle arthropathy.

INTRODUCTION: Haemophilic ankle arthropathy may cause joint bleeding, pain, stiffness, erosion and progressive motion limitations, including a decreased range of motion (ROM) secondary to anterior osteophyte impingement. AIM: The purpose of this study was to investigate changes in the ROM and symptoms after synovectomy and anterior osteophyte resection for haemophilic ankle arthropathy. METHODS: We retrospectively reviewed 41 ankles in 35 patients with haemophilic arthropathy who underwent arthroscopic and/or open synovectomy. The mean follow-up period was 59.5 months. Indications for the procedure included a lack of improvement with conservative management, and the presence of haemarthrosis and arthralgia. We assessed radiographic images, ankle joint range of motion, the American Orthopaedic Foot and Ankle Society (AOFAS) Ankle-Hindfoot score and patients' subjective satisfaction preoperatively and at the last follow-up. RESULTS: Arthroscopic synovectomy was performed in 32 ankles, open synovectomy in 6, and arthroscopic synovectomy with additional mini-open debridement in 3. Ankle dorsiflexion improved from a mean of 2.7° preoperatively to a mean of 7.5° at the final follow-up (P = 0.003), whereas plantar flexion improved from a mean of 30.7° preoperatively to a mean of 32.7° at the final follow-up (P = 0.276). The AOFAS score improved from 62.2 preoperatively to 79.1 at the final follow-up (P < 0.001). Patient satisfaction was "excellent" in 11 ankles, "good" in 22, "fair" in 3 and "poor" in 5. CONCLUSION: Arthroscopic and/or open synovectomy with anterior osteophyte resection and early rehabilitation in adolescents and adults with haemophilic ankle arthropathy showed improved ankle dorsiflexion and AOFAS scores.

Assessment of haemophilic arthropathy through balance analysis: a promising tool.

The purpose of this study was to develop a tool able to distinguish between subjects who have haemophilic arthropathy in lower limbs and those who do not by analyzing the centre of pressure displacement. The second objective was to assess the possible different responses of haemophiliacs and healthy subjects by creating a classifier that could distinguish between both groups. Fifty-four haemophilic patients (28 with and 26 without arthropathy) and 23 healthy subjects took part voluntarily in the study. A force plate was used to measure postural stability. A total of 276 centre of pressure displacement parameters were calculated under different conditions: unipedal/bipedal balance with eyes open/closed. These parameters were used to design a Quadratic Discriminant Analysis classifier. The arthropathy versus non-arthropathy classifier had an overall accuracy of 97.5% when only 10 features were used in its design. Similarly, the haemophiliac versus non-haemophiliac classifier had an overall accuracy of 97.2% when only 7 features were used. In conclusion, an objective haemophilic arthropathy in lower limbs evaluation system was developed by analyzing centre of pressure displacement signals. The haemophiliac vs. non-haemophiliac classifier designed was also able to corroborate the existing differences in postural control between haemophilic patients (with and without arthropathy) and healthy subjects.

Using the Hemophilia Joint Health Score for assessment of children: Reliability of the Spanish version.

INTRODUCTION: Numerous measuring instruments for the evaluation of hemophilic arthropathy have been developed. One of the most used systems is the Hemophilia Joint Health Score (HJHS) given its sensitivity to clinical changes appearing in the joints because of recurrent hemarthrosis. OBJECTIVE: Assessing the interrater reliability, using the Spanish version of the HJHS (version 2.1) in children with hemophilia. DESIGN: Reliability study to assess the interrater reliability of the Spanish version of HJHS. METHODS: A sample of 36 children aged 7-13 years diagnosed with hemophilia A or B was used. Two physiotherapists performed physical assessments with the Spanish version of the HJHS. Descriptive statistics (range, mean, standard deviation) and the analysis of interrater reliability were calculated. RESULTS: The interrater reliability was heterogeneous since the Kappa coefficient range (ĸ), although significant (p < 0.001), ranged 0.31-1.00 in the variables of HJHS (swelling, duration of swelling, muscle atrophy, crepitus on motion, flexion loss, extension loss, joint pain, strength, and global gait). In assessing the bias of observers with the Bland and Altman method, the observer 1 scored 0.41 (CI [-0.67, 1.49]) units above observer 2, and the difference between the two was significant (t(36) = 4.48), p < 0.001). CONCLUSIONS: The interrater reliability of the Spanish population version of the HJHS is high. This scale should be used generically in evaluating musculoskeletal pediatric patients with hemophilia.

Rapid inflammation and early degeneration of bone and cartilage revealed in a time-course study of induced haemarthrosis in haemophilic rats.

OBJECTIVES: Detailed knowledge of the sequential cell and tissue responses following haemarthrosis is important for a deep understanding of the pathological process initiated upon extensive bleeding into the joint causing haemophilic arthropathy (HA). The underlying pathobiology driving haemarthrosis towards HA has been difficult to establish in detail, although animal models have shed light on some processes. Previous studies have focused on a single or a few distant time points and often only characterizing one tissue type of the joint. The objective of this study was, therefore, to carefully map early onset of synovitis and HA following induced haemarthrosis. METHODS: One hundred and thirty haemophilia A rats were subjected to induced haemarthrosis or a sham procedure in full anaesthesia and euthanized from 30 min to 7 days after the procedure. Pathological changes of the joints were visualized using micro-computed tomography, histology and immunohistochemistry. RESULTS: Synovitis developed within 24 h and was dominated by myeloid cell infiltrations. Cartilage and bone pathology were evident as early as 48-96 h after haemarthrosis, and the pathology rapidly progressed with extensive periosteal bone formation and formation of subchondral cysts. CONCLUSION: Fast, extensive and simultaneous cartilage and bone degeneration developed shortly after haemarthrosis, as shown by the detailed mapping of the early pathogenesis of HA. The almost immediate loss of cartilage and the pathological bone turnover suggest a direct influence of blood on these processes and are unlikely to be attributed simply to an indirect effect of inflammation.

Investigating the relationship between the HJHS and HAL in routine clinical practice: A retrospective review.

INTRODUCTION: Comprehensive musculoskeletal assessment for monitoring joint health in haemophilia includes both physical assessment with Haemophilia Joint Health Score (HJHS) and assessment of self-reported function by Haemophilia Activities List (HAL). METHODS: Correlation between physical assessment and joint function was undertaken between HJHS and HAL in patients with SHA and SHB who had both assessments at the same visit over a one-year period. RESULTS: Data from 120 patients (96-SHA/24 = SHB) with a median age 33 years (range 19-73) were included. Median total HJHS was 19, increasing with age: 18-30 years-7, 31-50 years-25 and 51-73 years-44. Similarly, median total HAL score was 80 with decreased function associated with increasing age: 18-30 years-90.4, 31-59 years-71.7, 51-73 years-49.5. Median Total HJHS and HAL demonstrated strong correlation (rs  = 0.66, P < 0.01). Moderate-to-strong correlations were seen across the entire age group between the HJHS LL and UL subtotals and corresponding limb HAL domains. Within age groups, correlations were less significant particularly for the upper UL domains in HAL and the UL HJHS score. The wide range of ROM in joints categorized as markedly affected (ie, ROM loss score = 3) highlights the potential ceiling effect of this domain score and its use in chronically damaged joints. CONCLUSION: HJHS and HAL showed moderate-to-strong correlation with discrepancy in some individual patients. Prospective studies are required to better understand the clinical utility of both especially in severe joint disease where HAL may have a potential advantage.

Impact of Exercise/Sport on Well-being in Congenital Bleeding Disorders.

Physical activity provides many benefits in patients with congenital bleeding disorders. Patients with hemophilia are encouraged to participate in exercise and sports, especially those patients receiving prophylaxis. Several publications and guidelines have explored this issue in hemophilia patients, evaluating in particular the impact of physical activity on patients' well-being and quality of life. The other rare congenital bleeding disorders are less studied; they are heterogeneous in terms of clinical bleeding phenotype, incidence of hemarthrosis, and arthropathy. Furthermore, prophylaxis in these patients is less common than in hemophilia patients, which must be considered when choosing the type of physical and sporting activity. In this review, the authors have analyzed the literature focusing their attention on those rare coagulation disorders that may be complicated by arthropathy and the role of exercise and sports in this context.

Physiotherapy Treatments in Musculoskeletal Pathologies Associated with Haemophilia.

The aim of this study is to offer physiotherapists a synthesis of the main therapeutic tools available for the treatment of musculoskeletal pathologies in patients with haemophilia, according to the scientific literature. Although bleeds are recognised as no longer being a cause of death for people with haemophilia, the accompanying musculoskeletal injuries now represent the main problem associated with this disorder. There is a lack of clear guidelines to date regarding the physiotherapy treatment of these disorders. We performed a keyword searches of Pubmed, Scopus, Sciencedirect, Cochrane and PEDro databases. In total, 555 references were retrieved, of which only 55 fulfilled the inclusion criteria. Publications were grouped by the main symptoms caused by haemophilia and the physiotherapy treatments available. The literature reviewed shows that physiotherapists have a range of therapeutic tools at their disposal for the treatment of the main musculoskeletal disorders suffered by patients with haemophilia. Physiotherapy interventions act upon inflammation and pain, as well as favouring the reabsorption of haematomas, preventing muscle fibrosis and joint ankylosis and recovering the joint range from prior to the lesions. Also, these interventions help prevent muscle atrophy and provide patients with the optimal physical conditions for facing the small and repetitive injuries that, over time, can have a detrimental effect on their quality of life. CONCLUSION: Haemophilic patients suffer from a series of musculoskeletal disorders, which are associated with important functional disability. Physiotherapy and adapted sports are essential for decreasing disability and improving the quality of life of affected patients.

Nano-evidence for joint microbleeds in hemophilia patients.

The concept of joint microbleeding in hemophilia patients was first proposed over 10 years ago. This was based on unexpected abnormalities found in medical imaging studies of asymptomatic joints. Since then, there have been no published studies confirming the presence of joint microbleeds. This critique will review the evidence for and against joint microbleeding in hemophilia patients and the potential implications.

Vascular Permeability and Remodelling Coincide with Inflammatory and Reparative Processes after Joint Bleeding in Factor VIII-Deficient Mice.

Vascular remodelling is a prominent feature of haemophilic arthropathy (HA) that may underlie re-bleeding, yet the nature of vascular changes and underlying mechanisms remain largely unknown. Here, we aimed to characterize synovial vascular remodelling and vessel integrity after haemarthrosis, as well as temporal changes in inflammatory and tissue-reparative pathways. Thirty acutely painful joints in patients with haemophilia (PWH) were imaged by musculoskeletal ultrasound with Power Doppler (MSKUS/PD) to detect vascular abnormalities and bloody effusions. Nineteen out of 30 painful joint episodes in PWH were associated with haemarthrosis, and abnormal vascular perfusion was unique to bleeding joints. A model of induced haemarthrosis in factor VIII (FVIII)-deficient mice was used for histological assessment of vascular remodelling (α-smooth muscle actin [αSMA] expression), and monitoring of in vivo vascular perfusion and permeability by MSKUS/PD and albumin extravasation, respectively. Inflammatory (M1) and reparative (M2) macrophage markers were quantified in murine synovium over a 10-week time course by real-time polymerase chain reaction. The abnormal vascular perfusion observed in PWH was recapitulated in FVIII-deficient mice after induced haemarthrosis. Neovascularization and increased vessel permeability were apparent 2 weeks post-bleed in FVIII-deficient mice, after a transient elevation of inflammatory macrophage M1 markers. These vascular changes subsided by week 4, while vascular remodelling, evidenced by architectural changes and pronounced αSMA expression, persisted alongside a reparative macrophage M2 response. In conclusion, haemarthrosis leads to transient inflammation coupled with neovascularization and associated vascular permeability, while subsequent tissue repair mechanisms coincide with vascular remodelling. Together, these vascular changes may promote re-bleeding and HA progression.

Postural control during a transition task in haemophilic children, adolescents and young adults with haemophilic ankle arthropathy.

BACKGROUND: The aim of this study was to determine whether young haemophilic boys with and without MRI-based signs of ankle arthropathy demonstrate reduced balance ability during a transition task with eyes open and eyes closed. METHODS: Thirty-four haemophilic bodies and 28 typically developing boys aged 6-20 years participated to this study. Structural integrity of the tarsal foot joints of all haemophilic boys was assessed with MRI. All participants performed a standard transition task from double-leg stance to single-leg stance with eyes open and eyes closed. Comparison of balance features derived from the centre of pressure displacement captured by a single force platform was performed between the different haemophilia subgroups and sex-age-height matched peers. FINDINGS: The haemophilic boys without signs of arthropathy presented only a higher intermediate phase velocity during the eyes closed condition (P = .05). The haemophilic boys with signs of arthropathy had significantly higher displacement after the time to new stability point, and 95% Ellipse Sway Area and Balance Area compared to their matched peers during eyes open test (P < .05). Similar findings were observed during the eyes closed test for the displacement after the time to new stability point and 95% Ellipse Sway Area (P < .05). No significant differences were observed between affected and non-affected side of the unilateral affected patients. INTERPRETATION: We suggest that the pathophysiological cascade associated with chronic bleeding episodes should not be considered as a "simple" musculoskeletal injury, hence more as a complex neurophysiological dysfunction which may originate both from unilateral and bilateral deterioration of the musculoskeletal system.

Assessments of pain, functional impairment, anxiety, and depression in US adults with hemophilia across patient-reported outcome instruments in the Pain, Functional Impairment, and Quality of Life (P-FiQ) study.

INTRODUCTION: Pain, functional impairment, anxiety, and depression associated with joint disease may affect health-related quality of life (HRQoL) in people with hemophilia. OBJECTIVE: To report detailed patient-reported outcomes (PRO) assessments related to HRQoL in participants in the Pain, Functional Impairment, and Quality of Life (P-FiQ) study. METHODS: Pain and HRQoL were assessed via PRO instruments in US adult males with hemophilia A or B and a history of joint pain or bleeding. PRO instruments included EQ-5D-5L with visual analog scale, Brief Pain Inventory v2 Short Form, SF-36v2, and Hemophilia Activities List. Instrument domain and item responses were described. RESULTS: Responses were collected from 381 adult males with a median age of 34 years. Pain was observed across instruments and affected daily activities and quality of life. Respondents reported functional impairment that limited the kind of work and activities they participated in, with activities involving the lower extremities being most affected. A high prevalence of mental health disorders was identified across instruments. CONCLUSIONS: Pain and HRQoL were evaluated using multiple PRO instruments, which vary in timescales of assessment and levels of detail. More consistent clinical assessments and patient dialog regarding pain and aspects of HRQoL may help drive improved outcomes.

What can we learn from using formal patient-reported outcome instruments to assess pain, functional impairment, anxiety, and depression in US adults with hemophilia?

People with hemophilia frequently suffer from arthropathy that leads to pain and functional impairment, ultimately resulting in reduced quality of life. The impact of pain and functional impairment on the lives of people with hemophilia was explored in the Pain, Functional Impairment, and Quality of Life (P-FiQ) study. Various patient-reported outcome (PRO) instruments were employed to assess the effect of pain and functional impairment on multiple aspects of health in people with hemophilia. The results presented in this supplement include detailed observations from PRO instruments regarding pain, functional impairment, anxiety, and depression, an analysis of the differences in health-related quality of life across subgroups of patients defined by demographic and treatment-related characteristics, and results of a modeling analysis to identify patient factors which influence perceptions of pain and functional impairment, independent of joint status. These data provide insights into how the results from PRO assessments may be used to evaluate outcomes for people with hemophilia in the clinical and research settings.