Biochemical marker research in hemophilic arthropathy: A systematic review

Hemophilic arthropathy (HA) causes major morbidity. Breakthrough therapies reduce the bleeding frequency tremendously, but well-defined joint outcome assessments with a focus on early changes and subclinical damage are lacking. Biomarkers reflecting joint tissue turnover/inflammation might be useful to predict invalidating arthropathy. This systematic review summarized and categorized publications on blood/urinary biomarkers in HA to provide leads for implementation. A PubMed/EMBASE search was performed on September 9, 2019. All publications were assessed and allocated to one or several BIPED-categories, based on the utility of biomarkers. Of the initial 1307 publications found, 27 were eligible for inclusion. The majority (81%, n = 32/42) was cross-sectional in design, including relatively small numbers of patients (median 44, interquartile range 35-78). Fourteen percent (n = 6/42) investigated dynamic changes around a bleeding or treatment. Only two studies investigated the prognostic value of biomarkers. Most promising biomarkers were serum Coll2-1, COL-18N, COMP, C1,2C, C2M, CS846, MIF, plasma sVCAM-1 and urinary CTX-II. Comparing performances and pooling data was not possible due to heterogeneity. Currently, biomarker research in HA is still in an explorative stage and not yet sufficient for translation into daily practice. Clearly, larger homogeneous longitudinal studies in well-defined populations should be performed for further development.