Interleukin-6 (IL-6) may be useful as a sensitive biomarker for the identification of acute and recent bleeding events in patients with hemophilia, according to a study published in Thrombosis and Haemostasis.

The benefit of modern hemophilia therapeutics is their ability to prevent spontaneous bleeding episodes. Studies using transgenic hemophilic mice reveal that even minor injuries can trigger extensive hematomas in the absence of a functioning clotting cascade. Because bleeding is often prolonged with accompanying inflammation, joint and muscle bleeds can cause significant problems in mobility over time. 

“Symptoms of inflammation in hemophilia patients such as deregulated innate immune cells and elevated [C-reactive protein] suggest that the clinical and subclinical injuries sustained by hemophiliacs represent a recurrent inflammatory stimulus,” the authors of the study wrote. 

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They hence assessed the plasma levels of IL-6 and other biomarkers in patients with hemophilia (with or without recent bleeds) and compared them with those found in healthy blood donors. The research team drew blood from 59 adult male patients with hemophilia A or B during routine clinical visits and obtained control samples from healthy male blood donors. 

Read more about hemophilia etiology 

There was also another component of the trial, involving factor VIII knockout mice and wild-type control mice. To simulate joint injury, some mice were punctured with a 30G hypodermic needle underneath the patella of the right knee joint, causing significant hematomas. All mice were eventually euthanized for blood studies, including analysis of plasma levels of IL-6 and other biomarkers. 

The authors of the study discovered that IL-6 was a significant biomarker of bleeding in human patients who suffered from an acute bleeding episode, as well as in transgenic hemophilic mice who were punctured at the right knee. IL-6 levels remained high until a few weeks later, when the hematoma was eventually replaced by arthrofibrosis. 

“We, therefore, postulate that IL-6 is a sensitive marker of hemorrhage in hemophilia patients that can complement diagnostic imaging such as ultrasound, [computed tomography] scans, or magnetic resonance imaging in complex cases such as swollen or painful joints,” the authors of the study concluded. 


Knowles LM, Wolter C, Menger MD, et al. Activation of the acute-phase response in hemophiliaThromb Haemost. Published online April 10, 2023. doi:10.1055/a-2071-0477