Histidine-rich Glycoprotein as a Novel Predictive Biomarker of Postoperative Complications in Intensive Care Unit Patients

A Prospective Observational Study

Masahiko Oiwa; Kosuke Kuroda; Naoya Kawanoue; Hiroshi Morimatsu


BMC Anesthesiol. 2022;22(232) 

In This Article


After surgery, approximately 3–22% of patients develop postoperative complications.[1–4] Once a complication develops, the patient's hospitalization is prolonged, worsening the prognosis.[1] Previous studies have reported that white blood cell (WBC), C-reactive protein (CRP), procalcitonin (PCT), and presepsin (P-SEP) levels may be useful biomarkers for predicting postoperative complications.[5–13] However, standard biomarkers for predicting postoperative complications have not been established.

Histidine-rich glycoprotein (HRG) is an approximately 75-kDa glycoprotein mainly synthesized in the liver and present at a level of 60–150 μg/mL in healthy individuals.[14–17] HRG binds to various ligands and regulates coagulation fibrinolysis, the immune system, and angiogenesis.[17,18] In mice with sepsis, HRG levels decreased because of decreased production in the liver and increased degradation. Furthermore, decrease in HRG levels caused dysregulation of the coagulation-fibrinolysis system, abnormal neutrophil morphology, endothelial cell abnormalities, and immune thrombosis, leading to multiple organ failure.[17,19] Earlier clinical studies have reported that decrease in HRG levels may be a biomarker for sepsis,[16,20] ventilator-associated pneumonia,[21] preeclampsia,[22] and coronavirus disease 2019.[23]

However, the usefulness of HRG in perioperative management remains unknown. We hypothesized that HRG levels on postoperative day 1 (POD 1) could predict postoperative complications and conducted a prospective observational study to assess the usefulness of HRG as a biomarker for predicting postoperative complications.