The plasma concentration of citrullinated histone, a marker of neutrophil extracellular traps, is higher in patients with hemophilia than in people without a congenital bleeding disorder, a new study published in the Journal of Clinical Medicine found. Moreover, high serum levels of osteocalcin, a bone tissue formation marker, are more common in patients with hemophilia than in healthy people.

The concentrations of certain markers of bone turnover and neutrophil extracellular traps could, therefore, help identify patients with hemophilia who are at risk of developing hemophilic arthropathy and bone metabolic turnover abnormalities, the authors of the study concluded.

A team of researchers led by Lidia Gil, MD, PhD, from the Department of Hematology at Poznan University of Medical Sciences in Poland examined 60 patients with hemophilia to identify factors that predispose patients with hemophilia to bone loss and analyze the relationship between biomarkers of bone turnover, inflammation, and neutrophil trap and the clinical features of the disease, as well as its treatment and complications.

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The researchers assessed the levels of interleukin 6, citrullinated histone, osteocalcin, bone alkaline phosphatase, N-terminal procollagen type I propeptide, and C-terminal collagen type I telopeptide in the serum of the patients. The concentrations of osteocalcin and bone alkaline phosphatase are known to be dependent on the development of hemophilic arthropathy.

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The results showed that there were statistically significant differences in the concentrations of osteocalcin, bone alkaline phosphatase, C-terminal collagen type I telopeptide, and citrullinated histone according to the prophylaxis used.

Importantly, the concentration of citrullinated histone was higher in patients who received only on-demand therapy than in those who received prophylactic treatment, suggesting that the concentration of markers of bone turnover may depend on antihemorrhagic prophylaxis, the severity of the underlying disease, and the development of hemophilic arthropathy.

Hemophilic arthropathy is a common complication of hemophilia characterized by repetitive hemarthroses and progressive joint disease.


Czajkowska S, Rupa-Matysek J, Wojtasińska E, Nijakowski K, Surdacka A, Gil L. The profile of markers of bone turnover, inflammation and extracellular neutrophil traps on bone mass in haemophilia and the development of haemophilic arthropathy. J Clin Med. 2022;11(16):4711. doi:10.3390/jcm11164711