What is the most common cause of death in individuals with sickle cell disease?

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Common Cause of Death in Sickle Cell Disease

Acute chest syndrome is the leading cause of death in patients with sickle cell disease, accounting for a significant proportion of mortality across all age groups. 1, 2, 3

Primary Cause of Mortality

  • Acute chest syndrome (ACS) is definitively the most common cause of death in sickle cell disease patients, as established by the National Acute Chest Syndrome Study Group's multicenter analysis of 671 episodes. 1

  • ACS presents as a new segmental pulmonary infiltrate on chest radiograph accompanied by fever, respiratory symptoms, chest pain, or hypoxemia, and can rapidly progress to pulmonary failure and death. 4

  • The mortality rate from ACS is four times higher in adults compared to children, with fatal cases typically developing rapid pulmonary failure. 5

Mechanisms Leading to Death from ACS

In fatal ACS cases, the most common underlying causes are:

  • Pulmonary emboli (most frequent cause of death in ACS patients) 1

  • Infectious bronchopneumonia, which contributed to 56% of deaths in the National Acute Chest Syndrome Study 1

  • Pulmonary fat embolism, particularly in severe adult cases 1, 3

  • One-third of fatal ACS cases were associated with bacteremia 5

Additional Major Causes of Death

Beyond ACS, pulmonary complications collectively account for more than 20% of all deaths in sickle cell disease: 4

  • Pulmonary hypertension confirmed by right heart catheterization is an independent risk factor for mortality in adults with SCD 4, 6

  • Stroke can present with acute neurologic symptoms and requires urgent evaluation, as it represents another significant cause of mortality 4

  • Splenic sequestration may rapidly progress to shock and death if not promptly recognized and treated 4

Age-Related Mortality Patterns

  • Adults (≥20 years) have significantly more severe disease course and higher mortality from ACS compared to younger patients 1

  • Children typically present with milder, infection-related ACS, while adults develop severe disease often complicated by pulmonary fat embolism 5, 3

  • The death rate in adults is four times higher than in children when ACS occurs 5

Critical Clinical Pitfall

  • Nearly half of patients who develop fatal ACS were initially admitted for another reason, most commonly pain crisis, emphasizing the need for vigilant monitoring for respiratory complications in all hospitalized SCD patients 1

References

Research

Acute chest syndrome: sickle cell disease.

European journal of haematology, 2011

Research

Acute chest syndrome and sickle cell disease.

Current opinion in hematology, 1998

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Management of Sickle Cell Disease

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

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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