Activation of the Acute-Phase Response in Hemophilia

Abstract

To identify recurrent inflammation in hemophilia, we assessed the acute-phase response in the blood of patients with hemophilia A and B. 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 body mass index (BMI) > 30. Subgroup analysis of the remaining non-obese hemophilia patients (BMI 18-29.9) revealed a significant spike of IL-6, CRP and LBP in connection with a de-novo increase of soluble IL-6 receptor α (sIL-6Rα) in patients with bleeding events within the last month. Hemophilia patients that did not experience recent bleeding had IL-6, CRP and sIL-6Rα blood levels similar to healthy controls. We did not find increased IL-6 or acute-phase reactants in hemophilia patients with arthropathy or infectious disease. The 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 exhibited an extensive hematoma and a 150-fold increase of IL-6 blood levels within 7 days of the injury compared to needle-punctured control mice. Notably, IL-6 blood levels shrunk to a 4-fold elevation in hemophilia mice over controls after 28 days, when the hematoma was replaced by arthrofibrosis. These findings indicate that acute-phase reactants in combination with sIL-6Rα could be sensitive biomarkers for the detection of acute and recent bleeding events in hemophilia.

The good, the bad and the ugly of pain in haemophilia: Recent evidence on the epidemiology, molecular mechanisms and knowledge gaps preventing optimal treatment

“…62 Assessing the mechanisms underlying pain onset is central to identifying therapeutic interventions. The potential role of inflammation and oxidative stress, common responses to bleeding, is worth investigating 17,63 ; neuroinflammatory mechanisms may also have a role, although still to be clarified. 64 Exploring inflammation involvement and interaction with pain receptors in the context of haemophilia could provide valuable insights into the intricate pathways contributing to pain perception in this condition.…”