title: Biochemical markers of joint tissue damage increase shortly after a joint bleed; an explorative human and canine in vivo study.
abstract: OBJECTIVE
  Evaluation whether biomarkers of joint damage are sensitive to change shortly after a joint bleed in hemophilia patients and in a canine model of blood-induced joint damage.
  
  
  METHODS
  Blood and urine samples were collected from 10 hemophilia patients after they reported a joint bleed: within 2 days, after 3-5 days, and 12-14 days. Additionally, 90 days after the bleed a blood and urine sample was taken and considered to represent baseline condition. Commercial serum and urine biomarker assays were performed: urinary C-terminal telopeptide of type II collagen (uCTX-II), serum cartilage oligomeric matrix protein (sCOMP), serum cartilage cleavage product C1,2C, and serum chondroitin sulfate 846 (sCS846). The same panel of biomarkers was explored in dogs (n = 7) after induction of a first joint bleed by intra-articular blood injections. Biosamples were collected at baseline, day 2, 1 and 2 weeks later.
  
  
  RESULTS
  In hemophilia patients, levels of uCTX-II and sCS846 increased 5 days after joint bleeding when compared with baseline (+52%; P = 0.021 and +14%; P = 0.011, respectively). In dogs, uCTX-II increased statistically significant from day 2 to day 7 (from 75% to 155% of baseline; P = 0.018), and sCOMP from baseline to day 2 (+46%; P = 0.028).
  
  
  CONCLUSIONS
  This study demonstrates that biochemical markers of joint tissue damage increase shortly after a single joint bleed, both in humans with established hemophilic arthropathy (HA) and in an animal model of joint damage upon a first joint bleed. Biomarkers might be useful in monitoring the impact of a joint bleed and in evaluation of treatment of such bleeds.
authors.affiliation: Van Creveldkliniek, University Medical Center (UMC) Utrecht, Utrecht, The Netherlands; Department of Rheumatology & Clinical Immunology, University Medical Center (UMC) Utrecht, Utrecht, The Netherlands. Electronic address: L.F.D.vanVulpen-2@umcutrecht.nl.
authors.forename: L F D
authors.initials: LF
authors.lastname: van Vulpen
authors.affiliation: Van Creveldkliniek, University Medical Center (UMC) Utrecht, Utrecht, The Netherlands; Department of Rheumatology & Clinical Immunology, University Medical Center (UMC) Utrecht, Utrecht, The Netherlands. Electronic address: Monique.vanMeegeren@radboudumc.nl.
authors.forename: M E R
authors.initials: ME
authors.lastname: van Meegeren
authors.affiliation: Van Creveldkliniek, University Medical Center (UMC) Utrecht, Utrecht, The Netherlands. Electronic address: groosend@umcutrecht.nl.
authors.forename: G
authors.initials: G
authors.lastname: Roosendaal
authors.affiliation: Van Creveldkliniek, University Medical Center (UMC) Utrecht, Utrecht, The Netherlands; Department of Rheumatology & Clinical Immunology, University Medical Center (UMC) Utrecht, Utrecht, The Netherlands. Electronic address: n@thalie.nl.
authors.forename: N W D
authors.initials: NW
authors.lastname: Jansen
authors.affiliation: Department of Rheumatology & Clinical Immunology, University Medical Center (UMC) Utrecht, Utrecht, The Netherlands. Electronic address: J.M.vanLaar@umcutrecht.nl.
authors.forename: J M
authors.initials: JM
authors.lastname: van Laar
authors.affiliation: Van Creveldkliniek, University Medical Center (UMC) Utrecht, Utrecht, The Netherlands. Electronic address: R.Schutgens@umcutrecht.nl.
authors.forename: R E G
authors.initials: RE
authors.lastname: Schutgens
authors.affiliation: Department of Rheumatology & Clinical Immunology, University Medical Center (UMC) Utrecht, Utrecht, The Netherlands. Electronic address: S.Mastbergen@umcutrecht.nl.
authors.forename: S C
authors.initials: SC
authors.lastname: Mastbergen
authors.affiliation: Department of Rheumatology & Clinical Immunology, University Medical Center (UMC) Utrecht, Utrecht, The Netherlands. Electronic address: F.Lafeber@umuctrecht.nl.
authors.forename: F P J G
authors.initials: FP
authors.lastname: Lafeber
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D015415:Biomarkers / Q000097:blood / Q000652:urine; D004285:Dogs; D005260:Female; D006395:Hemarthrosis / Q000150:complications* / Q000209:etiology; D006467:Hemophilia A / Q000150:complications; D006801:Humans; D007592:Joint Diseases / Q000097:blood* / Q000175:diagnosis / Q000209:etiology / Q000652:urine*; D008297:Male; D008875:Middle Aged; D013997:Time Factors; D055815:Young Adult
chemical_list: D015415:Biomarkers
keywords: Arthropathy; Biochemical markers; Cartilage; Haemarthrosis