What causes fatigue in sickle cell disease and how is it managed?

Medical Advisory BoardAll articles are reviewed for accuracy by our Medical Advisory Board
Educational purpose only • Exercise caution as content is pending human review
Article Review Status
Submitted
Under Review
Approved

Last updated: June 3, 2025View editorial policy

Personalize

Help us tailor your experience

Which best describes you? Your choice helps us use language that's most understandable for you.

From the Guidelines

Fatigue in sickle cell disease is primarily caused by chronic anemia, as abnormal sickle-shaped red blood cells break down rapidly, leading to reduced oxygen delivery throughout the body. This condition is further complicated by other factors such as chronic inflammation, pain episodes, sleep disturbances, depression, and medication side effects 1. Management of fatigue in sickle cell disease involves a multi-faceted approach targeting both the disease and its symptoms.

Causes of Fatigue

  • Chronic anemia due to rapid breakdown of abnormal sickle-shaped red blood cells
  • Chronic inflammation
  • Pain episodes
  • Sleep disturbances
  • Depression
  • Medication side effects

Management of Fatigue

  • Blood transfusions may be used to increase hemoglobin levels when anemia is severe, aiming for hemoglobin levels above 8-9 g/dL
  • Disease-modifying medications like hydroxyurea increase fetal hemoglobin production, reducing sickling and improving energy levels
  • Supportive measures include maintaining adequate hydration, following a nutrient-rich diet with iron and folate supplementation, establishing consistent sleep patterns, engaging in moderate exercise as tolerated, and addressing pain with appropriate analgesics
  • Psychological support through counseling or cognitive behavioral therapy helps manage depression and anxiety that often accompany chronic fatigue
  • Regular monitoring of complete blood counts and reticulocytes allows for timely interventions when anemia worsens, helping to maintain quality of life and reduce fatigue burden 1.

Given the complexity of sickle cell disease and its management, it's crucial to follow the most recent guidelines, such as those from the American Society of Hematology, for the best outcomes in terms of morbidity, mortality, and quality of life 1.

From the Research

Causes of Fatigue in Sickle Cell Disease

  • Fatigue in sickle cell disease is a complex symptom that can be caused by various factors, including anemia, pain, and poor sleep quality 2.
  • The disease itself is characterized by the production of abnormal hemoglobin molecules, which can lead to red blood cells becoming stiff and sticky, causing various health complications, including fatigue 3.
  • The abnormal hemoglobin molecules can also lead to hemolysis, or the breakdown of red blood cells, which can result in anemia and fatigue 4.

Management of Fatigue in Sickle Cell Disease

  • Management of fatigue in sickle cell disease typically involves a comprehensive approach that includes pain management, hydration, and blood transfusions to improve oxygen delivery 3.
  • Hydroxyurea, a medication that increases the production of fetal hemoglobin, is commonly used to reduce the frequency and severity of pain crises and may also help alleviate fatigue 3, 4, 5, 6.
  • Other therapies, such as L-glutamine, crizanlizumab, and voxelotor, have been approved as adjunctive or second-line agents to help manage symptoms, including fatigue 4.
  • Hematopoietic stem cell transplant is the only curative therapy, but it is limited by donor availability, and best results are seen in children with a matched sibling donor 4.
  • Assessment of fatigue using validated scales, such as the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) questionnaire, can help healthcare professionals evaluate the intensity and determinants of fatigue in patients with sickle cell disease 2.

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.

Have a follow-up question?

Our Medical A.I. is used by practicing medical doctors at top research institutions around the world. Ask any follow up question and get world-class guideline-backed answers instantly.