Association Between Erythroferron and Perioperative Hemoglobin Levels in Patient Undergoing Heart Valve Surgery

In patients undergoing cardiac surgery, perioperative anemia is an important factor in surgical recovery. In addition to the low preoperative hemoglobin level, the delayed recovery of the postoperative hemoglobin level is an important problem affecting the incidence of postoperative anemia. Erythroferron is the early response to of the red blood cell production in stressful situations such as anemia, bleeding, and hypoxia. Therefore, it is thought that acute blood loss and systemic inflammatory reaction that inevitably occurs after cardiac surgery will synthesize erythroferron, which helps to restore hemoglobin level at postoperative period by promoting hematopoiesis by simultaneously inhibiting hepcidin and activating hematopoiesis.

In this study, the investigators will investigate the association between Erythroferron and perioperative hemoglobin levels in patient undergoing heart valve surgery.

Study Overview

• Status: Completed
• Conditions: Postoperative Anemia

• Study Type: Observational
• Enrollment (Actual): 150

Contacts and Locations

Study Locations

• South Korea
  • Seoul, South Korea
    • Yonsei University Health System, Severance Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Patient older than 20 years and undergong elective valvular heart surgery.

Description

Inclusion Criteria:

• Patients older than 20 years
• undergoing elective valvular heart surgery

Exclusion Criteria:

• Emergency operation
• Co-operation with other surgeries
• Patients with cardiogenic shock or ventricular-assist device (eg. ECMO, IABP)
• Patients requiring mechanical ventilator care in preoperative period
• Patient with severe chronic kidney disease (GFR(CKD-EPI) <30ml/min/1.73m2)
• Patients with preoperative infection status (Eg. Sepsis)
• Patients with acute bleeding status
• Hemoglobin concentration below 10g/dL
• Disease directly affecting hematopoiesis (eg. Leukemia, myeloma, aplastic anemia)
• Uncompensated liver cirrhosis, acute hepatitis, alcoholics
• Patients who participated in other clinical studies that could affect prognosis
• Patients who cannot understand the informed consent (eg. Foreigner)

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Lowest Erythroferron tertile group; The lowest concentration group will be Group1.
Highest Erythroferron tertile group; The highest concentration group will be Group2.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of hemoglobin concentration level after surgery in patients undergoing heart valve surgery	Compare the change of hemoglobin concentration level after surgery in patients undergoing heart valve surgery, by dividing the groups according to the level of erythroferron immediately after surgery. The amount of change will be compared based on the lowest level of hemoglobin during the time point after surgery. Since investigators planed to compare the recovery rate as well as the amount of recovery at each time point, investigators planed to record the change of hemoglobin at each time point based on the lowest hemoglobin level after surgery.	immediate after surgery, POD1, POD2, POD7, first outpatient vist after discharge (until 6 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in serum erythropoietin (EPO) level	Serum erythropoietin concentration will be measured using a quantitative ELISA assay and reported as mIU/mL. Changes in EPO level from baseline to 6 months will be compared among ERFE tertile groups.	From baseline (preoperative) to 6 months postoperatively
Change in serum hepcidin level	Serum hepcidin concentration will be measured using liquid chromatography-mass spectrometry (LC-MS) and reported as ng/mL.	From baseline (preoperative) to 6 months postoperatively
Change in hemoglobin (Hb) concentration	Hemoglobin will be measured using an automated hematology analyzer and reported as g/dL.	From baseline (preoperative) to 6 months postoperatively

Collaborators and Investigators

• Sponsor: Yonsei University

Study record dates

Study Major Dates

• Study Start (Actual): June 23, 2022
• Primary Completion (Actual): November 15, 2024
• Study Completion (Actual): September 15, 2025

Study Registration Dates

• First Submitted: May 9, 2022
• First Submitted That Met QC Criteria: May 17, 2022
• First Posted (Actual): May 20, 2022

Study Record Updates

• Last Update Posted (Estimated): October 2, 2025
• Last Update Submitted That Met QC Criteria: September 25, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Other Study ID Numbers: 4-2022-0260

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No