title: Blood-Induced Joint Damage: The Devastating Effects of Acute Joint Bleeds versus Micro-Bleeds.
abstract: OBJECTIVE
  Four days of blood exposure leads to irreversible cartilage damage in vitro. In contrast, intermittent intra-articular blood injections twice a week during 4 weeks (mimicking micro-bleeds) in a canine model resulted in transient damage only. In this study, it was evaluated whether acute joint bleeds are more harmful than micro-bleeds in a canine model of knee arthropathy.
  
  
  METHODS
  Seven dogs received 4 sequential daily intra-articular blood injections twice in 2 weeks (mimicking 2 acute 4-day joint bleeds). Seven other dogs received the same blood load but in a total of 8 injections intermittently over the 4-week period with at least 1 day in between (mimicking micro-bleeds over the same timespan). Contralateral knees served as controls. Ten weeks after the last injection cartilage matrix turnover and synovial inflammation were evaluated.
  
  
  RESULTS
  Only after the acute joint bleeds the release of newly formed and total (resident) cartilage matrix glycosaminoglycans were increased (P = 0.04 and P = 0.01, respectively). Furthermore, in animals with the acute joint bleeds cartilage glycosaminoglycan content was decreased (P = 0.01) and not in animals with micro-bleeds. Mild synovial inflammation was observed in both groups (both P < 0.0001) but was not different between groups.
  
  
  CONCLUSIONS
  In contrast to micro-bleeds, 2 acute joint bleeds lead to prolonged cartilage damage independent of the level of synovial inflammation. This model suggests that micro-bleeds are less devastating than acute joint bleeds with respect to joint damage, which might be of relevance to treatment of joint bleeds in clinical practice.
authors.affiliation: Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht, Netherlands ; Department of Hematology and Van Creveld Clinic, University Medical Center Utrecht, Utrecht, Netherlands.
authors.forename: Monique E R
authors.initials: ME
authors.lastname: van Meegeren
authors.affiliation: Department of Hematology and Van Creveld Clinic, University Medical Center Utrecht, Utrecht, Netherlands.
authors.forename: Goris
authors.initials: G
authors.lastname: Roosendaal
authors.affiliation: Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht, Netherlands ; Department of Hematology and Van Creveld Clinic, University Medical Center Utrecht, Utrecht, Netherlands.
authors.forename: Nathalie W D
authors.initials: NW
authors.lastname: Jansen
authors.affiliation: Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht, Netherlands.
authors.forename: Floris P J G
authors.initials: FP
authors.lastname: Lafeber
authors.affiliation: Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht, Netherlands.
authors.forename: Simon C
authors.initials: SC
authors.lastname: Mastbergen
keywords: acute joint bleed; cartilage; hemarthrosis; joint damage; micro-bleeds