In patients with nonsevere hemophilia A, systematically measured biomarkers cannot identify milder joint damage as seen on magnetic resonance imaging (MRI), according to findings from a cross-sectional study published in the Journal of Thrombosis and Haemostasis.
Although it is well known that individuals with nonsevere hemophilia A experience fewer joint bleeds compared with patients with severe hemophilia, these persons can nonetheless develop joint damage, with joint impairment and arthropathy often reported. To date, no analyses have assessed the association between biomarkers and MRI-evaluated joint damage in patients with nonsevere hemophilia A.
Realizing that the association between joint changes and biomarkers might offer valuable information on recognizing early joint changes in these patients, the researchers sought to examine the links between several selected biomarkers and their association with joint damage in this population. A number of promising biomarkers that reflect different pathologic processes were identified:
- Markers indicative of synovial inflammation and neoangiogenesis: osteopontin (OPN); vascular cell adhesion molecule-1 (VCAM-1);
- Markers indicative of the presence of basement membrane in the synovium: collagen type IV (C4); propeptide of type IV collagen (PRO-C4); and
- Markers indicative of cartilage turnover: serum cartilage oligomeric matrix protein (sCOMP); urinary carboxy-terminal telopeptides of type II collagen (uCTX-II); matrix metalloproteinase 9-mediated degradation of type II collagen (C2M); propeptide of type II collagen (PRO-C2).
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A subset of males with nonsevere hemophilia A were recruited from the Amsterdam University Medical Center and Erasmus University Medical Center Rotterdam, located in the Netherlands, for potential enrollment in the multicenter DYNAMO study. Male patients between 24 and 55 years of age with factor VIII (FVIII) levels of 2 to 35 IU/dL were evaluated.
The primary study outcome was joint status, which was calculated with use of the total MRI International Prophylaxis Study Group (IPSG) score. Secondary outcomes included the following:
- IPSG soft tissue subscore, which was indicative of early joint changes;
- IPSG osteochondral subscore, which demonstrated late joint changes;
- Individual cartilage component, which showed cartilage degradation; and
- Combined bone components, which comprised osteochondral cysts and bone erosions.
All participants received MRIs of 6 joints—their 2 elbows, 2 knees, and 2 ankles—at a single imaging session. All of the images were rated using the IPSG score. Total IPSG score involves the following 2 components:
- Soft tissue subscore: effusion, synovial hypertrophy, hemosiderin deposition
- Osteochondral subscore: surface erosions, cartilage degradation, subchondral cysts
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Forty-eight patients with nonsevere hemophilia A were enrolled in the study. The median participant age was
42 years; median baseline FVIII level was 10 IU/dL. Participants’ median IPSG score was 4, whereas median IPSG soft tissue subscore was 3 and osteochondral subscore was 0.
Study results showed that no strong associations were observed between the biomarkers evaluated, total IPSG scores, and soft tissue/osteochondral subscores.
“It seems too early for a role for biomarker analysis in the management of persons with [nonsevere] hemophilia, unless future studies identify biomarkers that are consistently associated with joint outcomes over time,” the researchers concluded.
Kloosterman FR, Zwagemaker AF, Bay-Jensen AC, et al. Poor correlation between biomarkers and MRI-detected joint damage in a cross-sectional study of persons with non-severe hemophilia A (DYNAMO study). J Thromb Haemost. Published online April 3, 2023. doi:10.1016/j.jtha.2023.03.030