Abstract
Background
People with hemophilia (PwH) or von Willebrand disease (VWD) are at risk of joint bleeding, which can lead to hemophilic arthropathy. Point-of-care musculoskeletal ultrasound (POC-MSKUS) is increasingly used to detect joint bleeds, but a comprehensive compilation of available independent scanning protocols and their respective measurement properties is missing.
Objectives
This study aimed to identify all existing POC-MSKUS scanning protocols and their reported measurement properties in PwH or people with VWD.
Methods
A scoping review was conducted using Embase, MEDLINE, and CINAHL (March 2025). Studies were included if they were peer-reviewed; published in English; used an experimental, observational, or review design; and examined POC-MSKUS for joint disease in children or adults with hemophilia A, hemophilia B, or VWD. Extracted data included scanning protocol characteristics and measurement properties such as reliability (interrater and intrarater), construct validity (convergent and known groups), criterion validity (concurrent and predictive), and responsiveness.
Results
Of 926 identified studies, 134 met the inclusion criteria (3 systematic reviews, 7 experimental studies, 75 observational studies, 39 narrative reviews, and 10 studies using other acceptable designs). Thirteen POC-MSKUS scanning protocols were identified. Among the 70 studies assessing measurement properties, reliability was reported in 12 studies, construct validity in 43 studies, criterion validity in 20 studies, and responsiveness in 5 studies. Predictive validity (2 studies) and responsiveness were the least reported properties.
Conclusion
Several POC-MSKUS scanning protocols exist, with predictive validity and responsiveness being the least established measurement properties. Future research should focus on prospective and experimental studies to establish these properties in POC-MSKUS protocols for PwH and people with VWD.
Keywords: hemophilia, von Willebrand disease, point-of-care testing, ultrasonography, hemarthrosis
Essentials
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Point-of-care musculoskeletal ultrasound (POC-MSKUS) detects hemophilic arthropathy.
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We identified existing POC-MSKUS scanning protocols and the reported measurement properties.
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POC-MSKUS protocols are evolving toward shorter evaluation times and greater accessibility.
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POC-MSKUS currently lacks evidence for predicting future outcomes or tracking change over time.
1. Introduction
Hemophilia is an X-linked rare bleeding disorder with an estimated global incidence of 30 cases per 100,000 males globally [1]. People with hemophilia (PwH) produce an insufficient amount of the clotting proteins, factor (F)VIII (hemophilia A) or FIX (hemophilia B), which can lead to recurrent joint bleeding if left untreated [2]. Similarly, people with von Willebrand Disease (VWD)—an inherited bleeding disorder characterized by a deficiency or dysfunction in von Willebrand factor—are at an increased risk of recurrent joint bleeding [3]. Recurrent joint bleeding (commonly affecting the ankles, knees, and/or elbows) can lead to hemophilic arthropathy (HA), a debilitating condition associated with pain, decrease in function and quality of life [[2], [3], [4]]. HA is characterized by synovial hypertrophy and osteochondral derangement, resulting in progressive deterioration of joint health status [4]. Joint bleeding has a lifetime incidence of 40% to 100% among PwH [5,6] and up to 53% among those with VWD [3]. Given the high incidence of joint bleeding among PwH and those with VWD, clinicians must be prepared to proactively detect and treat the early signs of HA to improve clinical outcomes.
Hemophilia treatment centers (HTCs) are one of the primary locations for assessment and management of PwH or VWD. Among the many tools used for assessment of HA at HTCs globally, ultrasound (US) is an increasingly used and promising tool [7,8]. In a systematic review among 14 studies, there was fair evidence recommending the use of US for early diagnosis of HA [7]. Since a full diagnostic joint US may not be feasible during a time-constrained HTC visit, several point-of-care musculoskeletal US (POC-MSKUS) scanning protocols, tailored to detecting HA, have been developed to expedite evaluation. POC-MSKUS refers to an examination done at the bedside or point-of-care to answer a limited set of clinical questions for commonly affected joints, which can be conducted by trained clinicians such as hematologists, physiotherapists, and advanced practice providers [7,9]. Although POC-MSKUS is a promising tool to detect early signs of HA and joint bleeding, evaluating the clinical utility of all available scanning protocols may be challenging and is further complicated by the lack of clear guidance on which measurement properties are available for each. The purpose of this scoping review was to identify all existing POC-MSKUS scanning protocols and their currently available associated measurement properties in PwH and VWD.
2. Methods
The information presented in this scoping review followed the Preferred Reporting Items for Systematic Review and Meta-Analysis Extension for Scoping Reviews (PRISMA-ScR) for reporting methodology [10], and the Consensus-based Standards for the Selection of Health Measurement Instruments (COSMIN) initiative checklist for reporting measurement properties [11].
2.1. Data sources and searches
One investigator (K.N.) performed the search strategy in consultation with a health research librarian. An example of our search strategy is presented in Figure 1. Searches were conducted in December 2023 and updated in March 2025 on Embase, CINAHL, and MEDLINE using variations of the following database specific subject heading and keywords: Point-of-Care Testing OR Ultrasonography AND Hemophilia A OR Hemophilia B OR von Willebrand Disease AND Joint Diseases OR Hemarthrosis OR Hemophilic Arthropathy.
Figure 1.
Search strategy performed for MEDLINE database.
2.2. Study selection
To ensure independent dual screening, 3 investigators (K.N., K.S., and N.B.) were involved in the title and abstract and full-text screening of all retrieved studies. One investigator (K.N.) screened all studies independently. To complete the second review, the remaining 2 investigators (K.S. and N.B.) independently screened a nonoverlapping, evenly divided subset of the same studies. Disagreements were resolved by consensus or by a third-party mediator where necessary. Studies were included using the following criteria:
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(1)
Peer-reviewed and published in the English language.
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(2)
Used any of the following study designs: experimental (randomized controlled trials [RCTs], non-RCTs, and pretest and posttest studies), observational (cross-sectional, retrospective, prospective, case series), and reviews (systematic reviews, narrative reviews, and, literature reviews).
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(3)
Included human participants of any age with any severity of hemophilia A, hemophilia B, or VWD.
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(4)
Addressed the use or development of a POC-MSKUS scanning protocol for the purpose of detecting joint disease affecting the ankles, knees, hips, elbows, and/or shoulders.
Case series were only considered if the sample size was ≥5 participants. Case reports/studies, qualitative studies, gray literature, conference abstracts/proceedings, editorials, and commentaries were excluded. POC-MSKUS was defined as “an ultrasound examination performed by a health care professional in which the purpose is to identify the presence or absence of a limited number of specific findings…” [8]. For the purposes of this study, joint diseases detected by POC-MSKUS may have included, but were not limited to, hemarthrosis, effusion, hypertrophic synovium, hemosiderin deposition, cartilage abnormalities, bone abnormalities, and/or muscle loss.
Title and abstract screening was initially conducted using the predefined eligibility criteria to exclude clearly irrelevant studies. If exclusion could not be justified due to insufficient information (eg, title only or limited methodological details in the abstract), the study was advanced to full-text screening. During full-text screening, articles were thoroughly assessed against the full eligibility criteria. Level of agreement between the 3 reviewers (K.N., K.S., and N.B.) using the screening criteria was assessed in a subsample of 20 titles and abstracts and 5 full-text articles using κ statistic, with an acceptable level of agreement set at κ of ≥0.8.
2.3. Data extraction
One investigator (K.N.) independently extracted data using a standardized form that was reviewed by 2 other investigators (K.S. and N.B). Extracted data included the study author, year of publication, patient population, sample characteristics (pediatric: <18 years; adult: ≥18 years), type of health care practitioner performing the US, joints scanned, total number of unilateral scans, evaluation time (minutes per joint), use of power Doppler (PD), application of a scoring system, and reported measurement properties. Additionally, specific scanning planes used in each scanning protocol were compiled and reported using a standard format based on anatomical plane (SAG, sagittal; COR, coronal; and AX, axial); and anatomical location (L1, proximal to joint line; L2, joint line; L3, distal to joint line; ANT, anterior; POST, posterior; MED, medial; CEN, center or midline; LAT, lateral) [12,13]. The total number of scans referred to unilateral scans across all joints examined. Evaluation time represents the average time (in minutes) required to scan a single joint, although this may vary by protocol depending on the number of scans required for a given joint. According to the COSMIN taxonomy, the extracted measurement properties and their respective aspects included reliability (interrater and intrarater reliabilities), construct validity (convergent and known groups validity), criterion validity (concurrent and predictive validity), and responsiveness [14]. The detailed definitions of the measurement properties were adapted from the COSMIN Taxonomy of Measurement Properties and are provided in Supplementary Table 1 [14].
2.4. Data synthesis and presentation
Information was presented in a table format featuring clinically relevant characteristics of each POC-MSKUS protocol included in data extraction. An additional table was created to display the number of times each measurement property was reported for each POC-MSKUS scanning protocol. If a study reported multiple measurement properties (eg, convergent validity, interrater reliability, and concurrent validity), each property was counted individually within its respective category.
3. Results
3.1. Sample characteristics
After deduplication, 928 studies were retrieved using our search strategy, which included 47 studies retrieved on our second search attempt in March 2025. Following title and abstract screening, 491 were excluded, leaving 364 for full-text review. Of these, 230 were excluded, resulting in 134 articles for data extraction, 14 of which were included from our second search attempt (Figure 2). Three studies were excluded since full texts were no longer available through their respective journal archives, despite efforts to locate them. The included studies comprised 3 systematic reviews, 3 RCTs, 4 non-RCTs, 75 observational studies (57 cross-sectional, 10 prospective, and 8 retrospective), 39 narrative reviews, and 10 studies using other designs (expert consensus, pilot studies, and published protocols). Among these, 19 studies focused exclusively on hemophilia A, 53 included both hemophilia A and B, and 8 examined hemophilia A, hemophilia B, and VWD. Regarding the study population, 26 studies focused solely on adults, 22 on pediatric patients, and 37 included both. Of the included studies, only 56 reported the type of health care practitioner who conducted the US assessment. Among these, 42 studies involved physicians, most commonly radiologists (n = 16), hematologists (n = 7), and orthopedists (n = 5). Additionally, 13 studies reported physiotherapists, and 4 reported sonographers as the practitioners who conducted the US assessment.
Figure 2.
Preferred Reporting Items for Systematic Review and Meta-Analysis Extension for Scoping Reviews flowchart.
3.2. Characteristics of POC-MSKUS scanning protocols
This study identified 13 POC-MSKUS scanning protocols (Table 1) [12,13,[15], [16], [17], [18], [19], [20], [21], [22], [23], [24], [25]]. The Haemophilia Early Arthropathy Detection with Ultrasound (HEAD-US) [20] was the most reported POC-MSKUS scanning protocol, cited in 82 studies, followed by the scanning protocol developed by Zukotynski et al. [15], cited in 30 studies. Seven protocols included scanning procedures for the ankles, knees, and elbows [[16], [17], [18], [19], [20],24,25], 4 covered only the ankles and knees [12,15,21,22], and 2 focused solely on a single joint [13,23]. The median number of unilateral scans across all scanning protocols was 13 (IQR, 10-18), with a range of 3 to 55, indicating that majority of protocols favored fewer scanning planes (Supplementary Table 2). A total of 35 unique scanning planes were reported for the elbow (median per protocol, 5; IQR, 3-6), with the most commonly used scanning planes being L2, SAG, ANT, LAT (n = 4); L1, SAG, POST, CEN (n = 4); and L3, SAG, POST, CEN (n = 3). For the knee, 38 distinct scanning planes were identified (median per protocol, 6; IQR, 3-6), with the most frequent being L1, SAG, ANT, CEN (n = 12); L1, AX, ANT, CEN (n = 8); and L2, SAG, ANT, MED (n = 6). The ankle had 29 different scanning planes reported (median per protocol, 4; IQR, 3-5), with the most frequent being L2, SAG, ANT, CEN (n = 8); L2, SAG, ANT, MED (n = 6); and L2, SAG, ANT, LAT (n = 6).
Table 1.
Characteristics point-of-care musculoskeletal ultrasound scanning protocols.
| Scanning protocol | Publication year | Joints included | Unilateral scans | Evaluation time (min/joint) | Power Doppler used | Scoring system available |
|---|---|---|---|---|---|---|
| Zukotynski et al. [15] | 2007 | Ankles; knees | 55 | 30 | Yes | No |
| Acharya et al. [16] | 2008 | Ankles; knees; elbows | 9 | - | Yes | No |
| Querol et al. [17] | 2008 | Ankles; knees; elbows | 8 | - | No | Yes |
| Keshava et al. [12] | 2009 | Ankles; knees | 41 | 30 | Yes | No |
| Melchiorre et al. [18] | 2011 | Ankles; knees; elbows | 14 | - | Yes | Yes |
| Querol et al. [19] | 2012 | Ankles; knees; elbows | 5 | - | No | No |
| Xavier et al. [13] | 2012 | Elbows | 31 | 30 | Yes | No |
| Martinoli et al. [20] | 2013 | Ankles; knees; elbows | 15 | 5 | No | Yes |
| Chung et al. [21] | 2017 | Ankles; knees | 10 | - | Yes | Yes |
| Kandagaddala et al. [22] | 2019 | Ankles; knees | 10 | 5 | Yes | No |
| Nag et al. [23] | 2019 | Knees | 4 | - | Yes | No |
| Volland et al. [24] | 2019 | Ankles; knees; elbows | 17 | 6 | Yes | Yes |
| Barnes et al. [25] | 2023 | Ankles; knees; elbows | 13 | 4 | Yes | Yes |
Characteristics of identified POC-MSKUS scanning protocols designed for detecting hemophilic arthropathy listed by year of publication. Characteristics include clinically relevant information (not exhaustive) for scope and feasibility of each respective POC-MSKUS scanning protocol. Unilateral scans indicate the total number of scanning views of each joint included on one side of the body.
-, lack of data using; POC-MSKUS, point-of-care musculoskeletal ultrasound.
Evaluation time was reported for 7 protocols, ranging from 4 to 30 minutes per joint. Six protocols included a scoring system to interpret US findings in which 9 different joint abnormalities were addressed. The 9 different joint abnormalities included were effusion, fibrotic septa, synovial hypertrophy, hemosiderin, bone erosion, osteophytes, bone remodeling, cartilage modifications, and abnormal vessels. Of these, 4 scoring systems incorporated PD to detect abnormal vascularity [18,21,24,25]. The most commonly evaluated joint abnormalities across scoring systems were synovitis or synovial hypertrophy [17,18,20,21], joint effusion [17,18,21], and osteochondral changes [18,20,21].
3.3. Measurement properties of POC-MSKUS scanning protocols
Measurement properties for all 13 scanning protocols were reported 101 times across 70 studies (Table 2; Supplementary Table 3). Construct validity was the most frequently reported measurement property at 53 times (25 for convergent validity and 28 for known groups validity) across 43 studies. Criterion validity was reported 22 times (20 for concurrent validity and 2 for predictive validity) across 20 studies. Reliability was reported 17 times (12 for interrater and 5 for intrarater) across 12 studies, and responsiveness was reported 9 times across 5 studies. Measurement properties were most frequently evaluated for the HEAD-US protocol, reported in 42 individual studies, followed by the protocols by Zukotynski et al. [15] in 9 studies.
Table 2.
Number of studies reporting measurement properties across each point-of-care musculoskeletal ultrasound scanning protocols.
| Scanning protocol | Publication year | Interrater reliability | Intrarater reliability | Convergent validity | Known groups validity | Concurrent validity | Predictive validity | Responsiveness | Total |
|---|---|---|---|---|---|---|---|---|---|
| Zukotynski et al. [15] | 2007 | 2 | 1 | 1 | 3 | 3 | - | 1 | 11 |
| Acharya et al. [16] | 2008 | - | - | 1 | - | 1 | 1 | 2 | 5 |
| Querol et al. [17] | 2008 | - | - | - | - | - | - | - | 0 |
| Keshava et al. [12] | 2009 | 3 | - | 3 | 1 | 2 | - | 1 | 10 |
| Melchiorre et al. [18] | 2011 | - | 1 | 1 | 5 | 1 | - | 2 | 10 |
| Querol et al. [19] | 2012 | - | - | - | 1 | - | - | - | 1 |
| Xavier et al. [13] | 2012 | 1 | - | 1 | - | 1 | - | 1 | 4 |
| Martinoli et al. [20] | 2013 | 4 | 1 | 16 | 14 | 11 | 1 | 2 | 49 |
| Chung et al. [21] | 2017 | - | - | 1 | - | - | - | - | 1 |
| Kandagaddala et al. [22] | 2019 | 1 | - | - | - | 1 | - | - | 2 |
| Nag et al. [23] | 2019 | 1 | - | - | 1 | - | - | - | 2 |
| Volland et al. [24] | 2019 | 1 | 1 | 2 | 1 | - | - | - | 5 |
| Barnes et al. [25] | 2023 | - | - | 1 | - | - | - | - | 1 |
Total number of studies reporting reliability, validity, and responsiveness across 13 POC-MSKUS scanning protocols. The definition of each measurement property is in accordance with the COSMIN Taxonomy of Measurement Properties, available elsewhere [14]. Each count indicates the presence of at least one report of the specified measurement property within a given study. Note: more than 1 measurement property or scanning protocol may be reported within 1 study and is counted separately, ie, 1 study may be represented as a count across multiple scanning protocols and/or measurement properties.
-, lack of data using; POC-MSKUS, point-of-care musculoskeletal ultrasound.
4. Discussion
In this scoping review, we identified 13 POC-MSKUS scanning protocols for the assessment of HA. Over time, POC-MSKUS scanning protocols have evolved to favor fewer scanning planes and shorter evaluation times. Predictive validity and responsiveness were the least reported measurement properties, indicating a gap in prospective observational and experimental studies. This underscores the limited understanding of how POC-MSKUS can predict future outcomes and track treatment-induced changes in PwH and patients with VWD overtime.
To the best of our knowledge, this is the first scoping review examining POC-MSKUS scanning protocols for evaluating HA. The heterogeneity of POC-MSKUS scanning protocols for HA suggests a lack of coordinated development and evaluation efforts. This is particularly evident in our review, which found that key measurement properties were missing from all but 1 scanning protocol, the HEAD-US [20]. Our findings highlight the need for a coordinated research effort to address these gaps for the future use of POC-MSKUS in clinical practice.
Our review provides a broad overview of the research landscape compared with systematic reviews [26], offering a more comprehensive view of the progression of POC-MSKUS over time and across studies. In the systematic review by Ligocki et al. [7], 5 POC-MSKUS scanning protocols were identified, all of which were captured in our review. Our review identified 3 additional protocols within the same timeframe likely due to differences in search and inclusion criteria. In 2017, Ligocki et al. [7] focused on clinical trials; we expanded our search to include observational studies and reviews. Lastly, since 2017, 5 new protocols have emerged [[21], [22], [23], [24], [25]], highlighting the timeliness of our review.
Systematic reviews play a crucial role in understanding the use of POC-MSKUS in hemophilia and informing clinical practice. Ligocki et al. [7] reviewed 14 studies and found fair evidence supporting US as an accurate tool for early diagnosis of HA, correlating with other clinical and imaging constructs and associating with joint functional status. However, without a meta-analysis, the overall reliability and validity of POC-MSKUS scanning protocols remain unclear. Given the breadth of studies evaluating measurement properties in our review, a meta-analysis could help consolidate findings and strengthen the evidence base.
Evaluating the measurement properties of a screening or assessment tool is essential to our understanding of the limitations of the tool in question. Majority of the studies in this review evaluated POC-MSKUS for convergent, known groups, and concurrent validity, likely due to the abundance of cross-sectionally designed observational studies (n = 57). In contrast, predictive validity (n = 2) and responsiveness (n = 5) were uncommonly reported, reflecting the limited number of prospective and experimental studies evaluating these measurement properties. Predictive validity is essential when evaluating whether a POC-MSKUS finding and/or summary score is clinically useful for predicting outcomes like risk of joint bleeds and early joint disease. Responsiveness is equally important for evaluating treatment efficacy over time. Without established estimates of responsiveness and meaningful change thresholds or scores, clinicians may not be able to confidently use POC-MSKUS to determine treatment effectiveness. Similarly, Ligocki et al. [7] determined, in their systematic review that there is insufficient evidence to conclude that US-detectable HA findings are sensitive to changes in therapy. It is important to note, however, insufficient evidence does not imply absence of effect but highlights the need for more robust studies.
Using POC-MSKUS for serial joint health monitoring and/or joint evaluation before and after an intervention is a clinically valuable approach. Interventions may include physiotherapy, factor replacement therapy, adjustments to prophylactic regimen dosing, or change from factor to nonfactor therapies, to name a few [27]. While osteochondral changes are typically not expected to improve with treatment, preventing further deterioration is often a key therapeutic goal. For instance, in a retrospective observational study, magnetic resonance imaging (MRI)–detected osteochondral damage was significantly greater in patients who initiated prophylaxis later (n = 18; mean age of initiation, 7.5 years) than that in those who began earlier (n = 15; mean age of initiation, 1.3 years), with an odds ratio of 6.3 (95% CI, 1.2-29.9; P = .02) [28]. Conversely, synovial hypertrophy has shown potential for reversibility. In an RCT evaluating the effects of intensive factor replacement in patients with severe hemophilia and hypertrophic synovium, those receiving intensive therapy (trough levels, 8%-12%) demonstrated significantly greater reductions in synovial thickening than those on standard prophylaxis (trough levels, 3%-5%) as measured by HEAD-US (−10.4% ± 15.4% vs −1.6% ± 5.9%; P = .003) [29]. Importantly, the clinical value of serial imaging lies not only in identifying positive responses but also in detecting disease progression or lack of therapeutic effect, each of which may have important implications for treatment planning.
Over time, POC-MSKUS scanning protocols have evolved to enhance efficiency and clinical utility. Earlier protocols typically included a higher number of scanning planes to detect joint bleeding, resulting in longer evaluation times—often approximately 30 minutes per joint—making them impractical for time-constrained clinical settings. Clinicians and patients may prefer protocols that balance comprehensiveness with feasibility, offering shorter evaluation times and simplified interpretation of US findings. Protocols such as the Universal Simplified US by Kandagaddala et al. [22] and HEAD-US by Martinoli et al. [20] have demonstrated that a reduced number of scanning planes can accurately detect HA when compared with that by MRI [22,30,31]. In our review, we identified the most commonly used scanning planes for the elbows, knees, and ankles and compiled them for reference (Supplementary Table 2). Our compilation of these scanning planes revealed that although 102 unique scanning planes (across the elbow, knee, and ankle) were identified, there were several common scanning planes across protocols. Additionally, 6 formal scoring systems were identified across the 13 scanning protocols reviewed, with the most consistently assessed joint abnormalities being synovial hypertrophy, joint effusion, and osteochondral changes. These shared features suggest the presence of a potential core set of joint abnormalities and scanning planes upon which standardized assessments could be based. Leveraging these common elements could potentially reduce inconsistencies across protocols and improve comparability of assessments across clinical settings.
PD was used in 10 of the 13 identified POC-MSKUS scanning protocols to assess synovial vascularity [12,13,15,16,18,[21], [22], [23], [24], [25]], a clinically relevant manifestation of vascular remodeling in HA [[32], [33], [34]]. In a prospective observational study of 26 adults with hemophilia, PD-detected synovial vascularity was associated with joint bleeding, further supporting its diagnostic value [33]. These findings suggest that the inclusion of PD in POC-MSKUS protocols could enhance the detection of secondary pathologic features of HA, particularly synovial vascular remodeling, which may be considered when selecting or designing scanning protocols.
While POC-MSKUS scanning protocols have progressively advanced in terms of efficiency and clinical utility, the absence of standardized approaches remains a major obstacle to their broader adoption in hemophilia care. This concern has been echoed globally in a consensus survey identifying that standardization of POC-MSKUS in bleeding disorder patient evaluation is a top priority, with strong support from both health care professionals and patient representatives [8]. These stakeholders advocated for the systematic integration of POC-MSKUS into routine practice across all HTCs, recognizing its potential to improve joint health monitoring and timely clinical decision making [8].
As efforts to standardize POC-MSKUS in clinical practice continue, protocol complexity, scoring method, feasibility, and targeted demographic (age and severity of arthropathy) are a few considerations. However, standardizing the use of a single protocol across all setting may not be the ideal path forward. Given the wide range of scanning protocols identified in this review, a sector-based approach offers a more pragmatic solution, allowing protocols to be tailored to the distinct needs of clinical care, research, and other contexts while leveraging the strengths of existing methods [35]. The International Prophylaxis Study Group has previously proposed a sector-based approach to adapt MRI scales to the specific needs of the sector in which they are applied [35]. In a busy HTC, a protocol that strikes a balance between thoroughness and feasibility would ideally use fewer scanning planes, include all targeted joints, and potentially include a scoring system for ease of interpretation to guide real-time treatment decisions. In contrast, research settings may incorporate a broader range of scanning planes and longer assessment times to support more detailed disease characterization. Tailoring protocols to the needs of each sector may improve their utility, ensuring that imaging approaches remain both practical and fit-for-purpose across diverse contexts.
The path toward standardization does not necessarily require the development of an entirely new and/or unified protocol. Refining existing protocols may represent a more practical and efficient approach. Notably, the HEAD-US protocol emerged as the most extensively studied among those identified, with all measurement properties considered in this review having been previously evaluated in the literature. However, it is important to note that this review does not interpret the results of measurement properties but merely states whether it has been evaluated at all. Therefore, the presence of a measurement property evaluation does not imply that it was sufficiently rigorous or yielded acceptable results. Given this limitation, advancing standardization efforts may be alternatively achieved by building on existing protocols and addressing gaps in reliability, validity, responsiveness, and feasibility.
Recently, new advancements in the use of US beyond the confines of assessment in clinic have emerged [36,37]. In a pilot study conducted by Aguero et al. [36], 10 adult PwH received teleguidance for joint self-imaging using a modified version of the Joint tissue Activity and Damage Exam US scanning protocol, resulting in an evaluation time of approximately 1 minute per scan [36]. The study by Aguero et al. [36] established that even inexperienced operators can conduct US scans efficiently if clear and accurate instructions are provided by a trained clinician. Additionally, some studies have addressed the use of artificial intelligence (AI)-assisted US imaging for the detection of joint bleeding and/or damage in PwH [[37], [38], [39]]. In a study by Tyrrell et al. [39], across 61,501 US images from joint examinations in PwH, their AI model correctly identified the presence of synovial recess distension (a key indicator of hemarthrosis) in 97% of images with a sensitivity of 97%, specificity of 96%, and area under the curve of 0.97. Advancements such as patient-administered guided US and AI-assisted US imaging may revolutionize patient care and reduce the barriers to timely health care access in the future.
Our findings were strengthened by our comprehensive search strategy, the application of PRISMA-ScR guidelines [10], and the classification of measurement properties using the COSMIN taxonomy [14]. Our search strategy was developed with recommendations from a health research librarian to capture as many relevant articles as possible. Abiding to the PRISMA-ScR guidelines ensures that our report meets the standards for replication and development of subsequent reviews on POC-MSKUS in hemophilia. The use of the COSMIN taxonomy allows for a clear understanding of the gaps in evidence for measurement properties to inform the development of future studies.
Our findings should be interpreted in light of some limitations. As a scoping review, this study was designed to map existing POC-MSKUS scanning protocols and their measurement properties, rather than assess their comparative effectiveness or provide clinical recommendations. Consequently, we did not statistically compare protocols or evaluate their relative utility in clinical practice. Additionally, due to the constraints in resources, data extraction was conducted by 1 investigator (K.N.), which may have introduced bias into the classification of measurement properties and interpretation of study details. To mitigate this risk, a standardized data extraction form was developed based on the COSMIN Taxonomy for Measurement Properties [14] and reviewed and approved by all 3 investigators (K.N., K.S., and N.B.) prior to data extraction.
5. Conclusion
In conclusion, this scoping review identified 13 currently available POC-MSKUS scanning protocols, each using a range of acquisition techniques and measurement assessments. However, evidence supporting predictive validity and responsiveness was notably lacking, emphasizing the need for prospective observational and experimental studies in PwH and VWD. The absence of standardization across protocols further highlights the need for united and inclusive research efforts as we march forward. This review provides a comprehensive synthesis of the current landscape, highlighting areas of commonality and divergence to support future research and collaborative initiatives focused on developing evidence-based clinical practice guidelines that can guide the standardized use of POC-MSKUS across HTCs. As a potential way forward, a sector-based approach, tailored to available resources and specific contexts, may offer a practical and efficient path for advancing POC-MSKUS practice.
Acknowledgments
We thank the invaluable contribution and guidance from members of the Imaging Expert Working Group of the International Prophylaxis Study Group throughout the conception and conduct of this study. Funding for activities of the International Prophylaxis Study Group is provided by independent education grants from Bayer Inc, BioMarin Pharmaceutical Inc, Novo Nordisk Healthcare AG, Pfizer, Sanofi, Sobi, and Takeda to the Hospital for Sick Children (SickKids) Foundation in Toronto, Canada.
Funding
This study was funded by the Imaging Expert Working Group of the International Prophylaxis Study Group.
Author contributions
All authors have made substantial contributions to the present study and have approved the final article. K.T.N. was responsible for data acquisition, data analysis and interpretation, drafting the article, article review and editing, final approval of the submitted version. N.B. and K.S. were responsible for study conception and design, data acquisition, article review and editing, final approval of the submitted version. A.v.D., P.B., H.P., and A.D. were responsible for study conception and design, article review and editing, and final approval of the submitted version. B.L. was responsible for article review and editing, and final approval of the submitted version.
Relationship Disclosure
K.S. has received honoraria/consulting fees from Pfizer Canada, Bayer, Shire, and Roche and a grant from Pfizer Canada.
Footnotes
Handling editor: Dr Johnny Mahlangu
The online version contains supplementary material available at https://doi.org/10.1016/j.rpth.2025.103185
Supporting Information
References
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