Sickle Cell Disease and Hemoglobin Levels
No, Sickle Cell Disease does not cause elevated hemoglobin levels—it causes chronic anemia with characteristically LOW hemoglobin values. Patients with SCD typically have baseline hemoglobin levels well below normal ranges, and this chronic anemia is a defining feature of the disease 1, 2, 3.
Baseline Hemoglobin Levels in SCD
Hemoglobin SS (HbSS) disease, the most severe form of SCD, is characterized by severe chronic anemia with typical hemoglobin levels of 60-90 g/L (6.0-9.0 g/dL), far below the normal range of 115-145 g/L 1.
Patients with sickle cell anemia have a variable hemoglobin level that may range from 7.0 to 11.0 g/dL in their steady state condition, which represents chronic anemia 3.
Other SCD variants like HbSC disease typically have higher baseline hemoglobin levels than HbSS but still remain below normal ranges 1.
Why Hemoglobin is Low in SCD
The low hemoglobin results from chronic hemolytic anemia, which is a fundamental pathophysiological process in SCD caused by extensive polymerization of hemoglobin S 4, 2.
Hemoglobin S polymerization causes damage to red cell membranes and cytoskeletons, leading to formation of irreversibly sickled cells and subsequent hemolysis, with damaged red cells removed by the reticuloendothelial system 4.
This chronic hemolysis is reflected by elevated unconjugated bilirubin levels, not elevated hemoglobin 4.
Clinical Significance of Low Hemoglobin
Lower hemoglobin concentrations are associated with worse clinical outcomes in SCD patients, including increased risk of cerebrovascular disease (0.4 g/dL lower), albuminuria (0.6 g/dL lower), elevated pulmonary artery pressure (0.9 g/dL lower), and mortality (0.6 g/dL lower) 5.
Meta-analyses demonstrate that even modest increases in hemoglobin concentration of 1 g/dL or greater result in 41% to 64% decreased risk of negative clinical outcomes 5.
Important Caveats About Hemoglobin Management
Never transfuse SCD patients to hemoglobin levels above 10 g/dL (hematocrit 30%) to reduce the risk of vaso-occlusion-related complications, stroke, and venous thromboembolism 6.
In splenic sequestration crisis, care must be taken to avoid acute overtransfusion to hemoglobin greater than 10 g/dL, as sequestered red cells may be acutely released from the spleen as the acute event resolves 6, 7.
The FDA-approved medication voxelotor is indicated for SCD based on its ability to increase hemoglobin levels, demonstrating that raising hemoglobin is a therapeutic goal, not a problem to avoid 8.
Common Pitfall
- Emergency providers must recognize that a precipitous drop in hemoglobin below baseline in recently transfused SCD patients may indicate hyperhemolysis syndrome, a life-threatening complication requiring immediate steroid therapy 9. Always screen SCD patients for recent transfusion history at ED presentation 9.