What causes increased erythrocyte (red blood cell) turnover?

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From the Guidelines

Increased red blood cell turnover is most commonly caused by hemolytic anemias, such as those seen in sickle cell disease, where red blood cells are destroyed prematurely, as evidenced by a significant drop in hemoglobin and accelerated HbS% increase with a concomitant fall in HbA posttransfusion 1.

Conditions Leading to Increased Red Blood Cell Turnover

  • Hemolytic anemias, including autoimmune hemolytic anemia and hereditary conditions like sickle cell disease, as defined by the American Society of Hematology 2020 guidelines for sickle cell disease: transfusion support 1
  • Physical trauma to red blood cells, such as in mechanical heart valves or microangiopathic conditions
  • Infections like malaria, which directly destroy red blood cells
  • Certain medications, including some antibiotics, antimalarials, and chemotherapy drugs, that can trigger hemolysis
  • Hypersplenism, where the spleen becomes overactive in removing blood cells
  • Blood loss from trauma, surgery, or gastrointestinal bleeding, which forces the body to produce more red blood cells, accelerating turnover

Laboratory Evidence of Increased Turnover

  • Elevated reticulocyte counts
  • Increased unconjugated bilirubin
  • Decreased haptoglobin
  • Elevated lactate dehydrogenase (LDH), as seen in hyperhemolysis defined by a rapid hemoglobin decline to below the pretransfusion level and rapid decline of the posttransfusion HbA level 1

Treatment Approach

Treatment depends on addressing the underlying cause rather than the turnover itself, and may include immunosuppressive therapy, such as IVIg and high-dose steroids, for life-threatening hemolysis, as recommended by the American Society of Hematology 2020 guidelines for sickle cell disease: transfusion support 1.

From the FDA Drug Label

Blood and Lymphatic System Disorders - suppressed hematopoiesis, anemia, aplastic anemia, pancytopenia, leukopenia, neutropenia, thrombocytopenia, agranulocytosis, eosinophilia, lymphadenopathy and lymphoproliferative disorders (including reversible)

The cause of increased red blood cell turnover is not directly stated in the label, but suppressed hematopoiesis and anemia are reported, which could be related to increased red blood cell turnover. However, the label does not provide a clear answer to the question. 2

From the Research

Causes of Increased Red Blood Cell Turnover

  • Sickle cell disease (SCD) is a condition that can lead to increased red blood cell turnover due to the abnormal shape of red blood cells, which can cause them to break down more quickly 3, 4, 5, 6, 7
  • Hydroxyurea, a medication used to treat SCD, can increase fetal hemoglobin production, which can help reduce the frequency of painful crises and other acute complications, but its effect on red blood cell turnover is not fully understood 3, 4, 5, 6, 7
  • Other factors that can contribute to increased red blood cell turnover include:
    • Hemolytic anemia, a condition where red blood cells are destroyed faster than they can be made 6
    • Vaso-occlusion, a condition where blood vessels become blocked, leading to tissue damage and increased red blood cell breakdown 6
    • Inflammation and oxidative stress, which can damage red blood cells and lead to increased turnover 5, 7

Mechanisms of Increased Red Blood Cell Turnover

  • Increased red blood cell turnover in SCD is thought to be due to a combination of factors, including:
    • Abnormal red blood cell shape and function 3, 4, 5
    • Increased hemolysis (red blood cell breakdown) 3, 4, 5
    • Inflammation and oxidative stress 5, 7
    • Vaso-occlusion and tissue damage 6

Clinical Implications of Increased Red Blood Cell Turnover

  • Increased red blood cell turnover can lead to a range of clinical complications, including:
    • Anemia 3, 4, 5, 6, 7
    • Fatigue 3, 4, 5, 6, 7
    • Shortness of breath 3, 4, 5, 6, 7
    • Increased risk of infections and other complications 3, 4, 5, 6, 7

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Hydroxyurea (hydroxycarbamide) for sickle cell disease.

The Cochrane database of systematic reviews, 2022

Research

Hydroxyurea in the sickle cell disease modern era.

Expert review of clinical pharmacology, 2024

Research

Hydroxyurea therapy for sickle cell anemia.

Expert opinion on drug safety, 2015

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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