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    Poster Networking

    Hemophilia and Rare Bleeding Disorders

    Poster Networking Session

    PB0154 - Blood-induced Inflammation in Hemophilia is Associated with Impaired Macrophage Function

    Sunday, June 25, 2023
    18:30 – 19:30 ET
    Room: Exhibition

      Co-Author(s)

    • LK

      Lynn M. Knowles

      Research Instructor
      Institute of Clinical Hemostaseology and Transfusion Medicine, Saarland University School of Medicine and Saarland University Medical Center
      Homburg, Saarland, Germany

      • Co-Author(s)

    • Carolin Wolter, MSc

      PhD Student
      Institute of Clinical Hemostaseology and Transfusion Medicine, Saarland University School of Medicine and Saarland University Medical Center
      Homburg, Saarland, Germany

    • MM

      Michael D. Menger

      Dean
      Institute for Clinical and Experimental Surgery, Saarland University School of Medicine and Saarland University Medical Center
      Homburg, Saarland, Germany

    • ML

      Matthias W. Laschke

      Professor
      Institute for Clinical and Experimental Surgery, Saarland University School of Medicine and Saarland University Medical Center
      Homburg, Saarland, Germany

    • FH

      Felix Haegele

      MD student
      Institute of Clinical Hemostaseology and Transfusion Medicine, Saarland University School of Medicine and Saarland University Medical Center
      Homburg, Saarland, Germany

    • Hermann Eichler, MD (he/him/his)

      Professor of Transfusion Medicine and Haemostaseology
      Institute of Clinical Haemostaseology and Transfusion Medicine, University and University Hospital of the Saarland, Homburg, Germany
      Homburg, Saarland, Germany

      • Presenting Author(s)

    • Jan Pilch, MD

      Assistant Professor
      Institute of Clinical Hemostaseology and Transfusion Medicine, Saarland University School of Medicine and Saarland University Medical Center
      Homburg, Saarland, Germany

    Background: We recently showed that the acute-phase response is elevated in hemophilia patients with acute and recent bleeds. In addition, we found that the regenerative capacity of hemophilia macrophages is reduced as is their ability to infiltrate clot and clear red blood cells.

    Aims: To determine if the inflammatory response to injury is deregulated in hemophilia after bleeding.

    Methods: To assess the effect of joint bleeding on inflammation, we induced a needle-puncture injury of the knee in transgenic mice with hemophilia A and harvested tissue samples over time for histological analysis.

    Results: While the needle puncture produced only a minor injury in the knees of coagulation competent control mice, we observed an extensive hematoma on day 1 and day 7 in the knees of hemophilia mice. By day 28, the hematoma was completely absorbed and replaced by fibrotic scaring. In contrast, injection of similar amounts of anticoagulated blood into the knees of coagulation competent wildtype mice were cleared much more rapidly. The prolonged presence of blood in the knee joints of hemophilia mice was associated with large depositions of hemosiderin-loaded macrophages. Notably, macrophages arrived with considerable delay in the punctured hemophilia joints compared to the blood-injected controls. The late arrival of macrophages was associated with a delayed clearance of neutrophils in the injured knees of hemophilia mice, which exacerbated blood-induced inflammation.

    Conclusion(s): Our data suggest that the deregulated function of hemophilia macrophages contributes to blood-induced inflammation and joint degeneration following hemarthrosis.