OC 20.4 - IL-6 is a Biomarker for Joint Bleeds in Hemophilia

Sunday, July 10, 2022

11:30 AM – 11:45 AM

Location: ExCel Center, ICC Capital Suite Room 1

Presentation Format: In-Person

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
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
LB

Lars Beyer

Medical Student
Institute of Clinical Hemostaseology and Transfusion Medicine
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
UG

Ulrich Grün

Senior Physician
Department of Orthopedic Surgery
Homburg, Saarland, Germany
HE

Hermann Eichler

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: Deregulated macrophage function in hemophilia correlates with impaired wound healing.

Aims: To identify the underlying inflammatory stimulus of macrophage activation in hemophilia.

Methods: To assess the acute-phase response in hemophilia patients, we collected blood from 59 adult patients with mostly severe hemophilia A and B compared to 54 healthy controls. To analyze inflammation in the context of bleeding, we induced a needle puncture injury in the knee joint of transgenic hemophilia mice.

Results: Compared to age- and weight-matched controls, blood levels of interleukin-6 (IL-6), C-reactive protein (CRP) and LPS-binding protein (LBP) were significantly elevated in the entire cohort of hemophilia patients but exhibited a particularly pronounced increase in obese hemophilia patients with a BMI > 30. Subgroup analysis of the remaining non-obese hemophilia patients (BMI of 18-29) revealed a significant spike of IL-6 and CRP in connection with a de-novo increase of soluble IL-6 receptor α (sIL-6Rα) in patients with a bleeding event within the last month. Hemophilia patients that did not experience recent bleeding, on the other hand, had IL-6, CRP and sIL-6Rα blood concentrations at levels similar to that seen in healthy controls. The pivotal role of IL-6 as a marker of bleeding in hemophilia was confirmed in hemophilia patients with acute bleeding events as well as in transgenic hemophilia mice after needle puncture of the knee, which caused an extensive hematoma and a nearly 150-fold increase of IL-6 blood levels within 7 days of the injury compared to needle-punctured control mice. Notably, the IL-6 blood levels shrunk to only a 4-fold elevation in hemophilia mice over controls after 28 days, when the hematoma was completely replaced by arthrofibrosis.

Conclusion(s): IL-6 is a potential biomarker for monitoring the extent and duration of joint bleeds in hemophilia and, as such, may be a predictor of bleeding-induced joint damage.