Background
Repeated haemarthroses affect approximately 90% of patients with severe haemophilia and lead to progressive arthropathy, which is the main cause of morbidity in these patients. Diagnostic imaging can detect even subclinical arthropathy changes and can impact prophylactic treatment. Magnetic resonance imagining (MRI) is generally the gold standard tool for precise evaluation of joints, but it is not easily feasible in regular follow-up of patients with haemophilia. The development of the standardized ultrasound (US) protocol for detection of early changes in haemophilic arthropathy (HEAD-US) opened new perspectives in the use of US in management of these patients. The HEAD-US protocol enables quick evaluation of the six mostly affected joints in a single study.
The aim of this prospective study was to determine the diagnostic accuracy of the HEAD-US protocol for the detection and quantification of haemophilic arthropathy in comparison to the MRI. We additionally intended to assess how HEAD-US holds up in comparison to currently used tools for regular joint status evaluation in clinical practice: clinical examination and patient's subjective grading of disease expression. We also evaluated correlation of some of the laboratory markers with MR imaging (vitamin D, ferritin, C-terminal telopeptide of type I collagen (CTX), N-terminal propeptide of type I procollagen (PINP), and cartilage oligomeric matrix protein (COMP)).
Hypotheses
H1: Evaluation of hemophilic arthropathy changes by the standardized US examination (HEAD-US) provides comparable results to the results of MRI.
H2: Ultrasound is a more accurate method for the detection and evaluation of early hemophilic arthropathy changes in comparison to the clinical evaluation and patient’s subjective grading.
H3: Results of laboratory analysis of s-CTX, s-PINP and s-COMP correlate with the results of imaging diagnostics for the presence or expression of hemophilic arthropathy.
Patients and methods
The study included 30 patients with severe haemophilia. Patient age ranged from 16 to 49 years. We evaluated their elbows, ankles and knees (overall 168 joints) by US using the HEAD-US protocol, clinically by Haemophilia Joint Health Score (HJHS) 2.1 and by MRI using the International Prophylaxis Study Group (IPSG) MRI score. Patients also filled subjective grade questionnaire and had blood taken for laboratory analysis. The correlation between the methods was determined using the Pearson's correlation coefficient.
Results
The results show that the overall HEAD-US score correlates very highly with the overall IPSG MRI score (r=0.92). The correlation is very high for the evaluation of the elbows and knees (r≈0.95), and only slightly lower for the ankles (r≈0.85). Analysis of laboratory results showed no correlation between the laboratory values and the presence or expression of haemophilic arthropathy.
Conclusions
HEAD-US protocol proved to be a quick, reliable and accurate method for the detection and quantification of haemophilic arthropathy in comparison to MRI.
Diagnostic accuracy of HEAD-US is considerably higher than the diagnostic accuracy of currently used methods of joint evaluation in clinical practice of management patients with severe haemophilia. Therefore, it can be confidently and safely included into the protocol of regular follow-up of these patients and to modify their prophylactic treatment regimen.
Investigated laboratory parameters show no correlation with the presence or expression of haemophilic arthropathy.
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