How is HbSC (Hemoglobin SC) disease milder than sickle cell anemia?

From the Guidelines

HbSC disease is generally milder than sickle cell anemia (HbSS) due to its unique genetic composition, resulting in less hemoglobin polymerization and sickling of red blood cells. This is evident from the study by 1, which highlights the differences in hemoglobin types and prevalence in the UK sickle cell disease population. According to the study, HbSC disease has a moderate severity, with approximately 50-55% of the hemoglobin being HbS, compared to 80-95% in HbSS.

Key Differences between HbSC and HbSS

• HbSC disease has a higher percentage of normal hemoglobin A, which helps maintain better red blood cell function and shape
• Patients with HbSC typically experience fewer painful crises, less severe anemia, and reduced risk of acute chest syndrome compared to those with HbSS
• The average hemoglobin level in HbSC patients is around 10-11 g/dL versus 7-8 g/dL in HbSS, as noted in the study by 1
• Life expectancy is also longer in HbSC disease, with many patients living into their 60s and 70s, while HbSS patients often have more limited lifespans

Clinical Implications

• HbSC patients still require regular medical monitoring as they can develop serious complications like retinopathy, avascular necrosis, and pregnancy complications, sometimes at rates similar to or even higher than in HbSS disease
• Treatment approaches are similar but often less intensive, focusing on pain management, hydration, and preventive care rather than chronic transfusions or hydroxyurea in many cases, as recommended by the guidelines in 1
• The goal of treatment is to reduce SCD-related complications and improve quality of life, while also considering the unique needs and risks associated with HbSC disease.

From the Research

Comparison of HbSC and Sickle Cell Anemia

• HbSC disease is generally considered milder than sickle cell anemia (SCA) 2, 3, 4
• Patients with HbSC disease tend to have less severe anemia, hemolysis, and inflammation compared to those with SCA 3, 4
• HbSC disease is associated with increased lipid determinations, whereas SCA patients exhibit more prominent anemia, hemolysis, leukocytosis, and inflammation 3

Clinical Manifestations

• Vaso-occlusive events and pain crises are common in both HbSC and SCA, but may be less frequent or severe in HbSC disease 2, 3, 4
• HbSC patients are more likely to experience thromboembolic complications, retinopathy, and renal papillary necrosis compared to SCA patients 4
• However, recent studies suggest that HbSC disease may be more clinically severe than previously recognized, with significant morbidities such as splenomegaly, retinopathy, avascular necrosis, and acute chest syndrome 5

Laboratory Parameters

• HbSC patients tend to have higher hemoglobin concentrations and less severe hemolysis compared to SCA patients 3, 4
• Hydroxyurea treatment has been shown to increase fetal hemoglobin and mean corpuscular volume, and reduce white blood cell count and absolute reticulocyte count in HbSC patients 2
• Laboratory parameters such as hematological, inflammatory, and anemia biomarkers can be useful in monitoring the clinical course of HbSC disease 3