Poor correlation between biomarkers and MRI-detected joint damage in a cross-sectional study of persons with nonsevere hemophilia A (DYNAMO study).

Abstract

BACKGROUND:

Persons with nonsevere hemophilia A (NSHA) experience less frequent joint bleeding than persons with severe hemophilia A, but may still develop joint damage. Biomarkers of cartilage and synovial remodeling can reflect ongoing pathologic processes that may precede or coincide with damage on joint imaging. If so, biomarkers may be an important diagnostic tool for joint damage in NSHA.

OBJECTIVE:

To assess the correlation between biomarkers and MRI-detected joint damage in persons with NSHA.

METHODS:

In a cross-sectional study, men with NSHA (factor VIII [FVIII], 2-35 IU/dL) were included. Participants underwent magnetic resonance imaging of elbows, knees, and ankles and blood and urine sampling for biomarker analysis on a single visit. The following biomarker(s) were analyzed in urine: CTX-II or serum: cartilage oligomeric matrix protein, chondroitin sulfate 846, vascular cell adhesion molecule 1, osteopontin (OPN), neo-epitope of MMP -mediated degradation of type II collagen, N-terminal propeptide of type II collagen, collagen type IV M, and propetide of type IV collagen. Spearman's rank correlations were calculated between these biomarkers and the total International Prophylaxis Study group (IPSG) score, soft-tissue subscore, and osteochondral subscore.

RESULTS:

In total, 48 persons with NSHA were included. Median age was 43 years (range, 24-55 years) and median FVIII was 10 IU/dL (IQR, 4-16 IU/dL). The median IPSG score was 4 (IQR, 2-9). Median IPSG soft-tissue subscores were 3 (IQR, 2-4) and osteochondral subscores were 0 (IQR, 0-4). No strong correlations were found between the studied biomarkers, total IPSG score, subsequent soft-tissue, and osteochondral subscores.

CONCLUSIONS:

In this study, selected biomarkers indicative of different aspects of hemophilic arthropathy showed no consistent correlation with IPSG scores. This suggests that systemically measured biomarkers are currently not suitable for identifying milder joint damage in NSHA, as observed on magnetic resonance imaging.

• Authors: Fabienne R Kloosterman, Anne-Fleur Zwagemaker, Anne C Bay-Jensen, Marjon H Cnossen, Marieke J H A Kruip, Frank W G Leebeek, Robert Hemke, Mario Maas, Karin Fijnvandraat, Samantha C Gouw, Michiel Coppens
• Journal: Journal of thrombosis and haemostasis : JTH (J Thromb Haemost) Vol. 21 Issue 7 Pg. 1813-1823 (Jul 2023) ISSN: 1538-7836 [Electronic] England
• PMID: 37019364 (Publication Type: Journal Article)
• Copyright: Copyright © 2023. Published by Elsevier Inc.

Chemical References

• Collagen Type II
• Biomarkers

Topics

• Male
• Humans
• Adult
• Hemophilia A (drug therapy)
• Cross-Sectional Studies
• Collagen Type II (therapeutic use)
• Magnetic Resonance Imaging (methods)
• Biomarkers