Does sickle cell trait (SCT) cause anemia?

Sickle Cell Trait Does Not Cause Anemia

Sickle cell trait (HbAS) is benign and does not cause anemia. 1, 2

Key Distinction: Trait vs. Disease

The critical difference lies in the genetic makeup:

• Sickle cell trait (HbAS) is the heterozygous carrier state where individuals inherit one normal hemoglobin gene and one sickle hemoglobin gene 2
• Sickle cell disease refers to homozygous (HbSS) or compound heterozygous states (HbSC, HbS-β-thalassemia) that cause clinical disease 1

Hemoglobin Composition in Sickle Cell Trait

Individuals with sickle cell trait have:

• 55-65% normal adult hemoglobin (HbA) 1
• 30-40% sickle hemoglobin (HbS) 1
• Mean corpuscular volume (MCV) < 3-5 fL 1
• Clinical classification: Benign 1

This hemoglobin composition is sufficient to maintain normal red blood cell function and prevents the chronic hemolysis that characterizes sickle cell disease 1

Clinical Implications

People with sickle cell trait are generally healthy and do not experience:

• Chronic hemolytic anemia 3
• Painful vaso-occlusive crises 1
• End-organ damage 1

Important Caveat for Anemia Workup

If a patient with known sickle cell trait presents with anemia that is unresponsive to iron therapy, consider alternative diagnoses:

• Thalassemia minor may coexist 1
• True iron deficiency from other causes 1
• Other unrelated hematologic conditions 1

The presence of sickle cell trait should not be assumed to be the cause of anemia in these patients 1

Contrast with Sickle Cell Disease

Unlike sickle cell trait, sickle cell disease causes severe chronic hemolytic anemia:

• HbSS patients typically have hemoglobin levels of 60-90 g/L 1
• Hemolysis results from extensive HbS polymerization, red cell membrane damage, and formation of irreversibly sickled cells 1
• This chronic anemia is a defining feature of the disease 2, 4