Diagnostic Confirmation of Sickle Cell Disease
Hemoglobin electrophoresis is the definitive diagnostic test for confirming sickle cell disease, though most patients will have been diagnosed previously through newborn screening programs or during acute presentations. 1, 2
Diagnostic Approach
Initial Screening Tests
When sickle cell disease is suspected but not yet confirmed, the diagnostic workup should include:
- Complete blood count (CBC) to identify normocytic anemia, elevated white blood cell counts (which may suggest underlying malignancy like leukemia), and assess baseline hemoglobin levels 1, 2
- Peripheral blood smear to visualize sickled red blood cells and assess cell morphology 3
- Reticulocyte count to evaluate bone marrow response and degree of hemolysis, as this reflects the appropriateness of erythropoietic response 1, 2
Confirmatory Testing
- Hemoglobin electrophoresis remains the gold standard confirmatory test, identifying hemoglobin S and distinguishing between different genotypes (HbSS, HbSC, HbS-β⁰-thalassemia) 1, 3
- This test should be reserved for select clinical scenarios when diagnosis is uncertain, as most patients in developed countries have established diagnoses through newborn screening 1, 2
- Patient race and underlying risk factors should guide the decision to perform electrophoresis in previously undiagnosed adults 1
Additional Laboratory Markers During Acute Presentations
When evaluating patients with suspected or confirmed sickle cell disease presenting acutely:
- Lactate dehydrogenase, bilirubin, aspartate aminotransferase may be elevated, reflecting hemolysis and vaso-occlusive crisis 1, 2
- Mean platelet volume, platelet count, and eosinophil counts may be elevated in acute ischemic complications 1
- These values help identify underlying causes but typically do not guide acute treatment decisions 1
Common Diagnostic Pitfalls
- Do not delay treatment to obtain hemoglobin electrophoresis in patients with clear clinical history of sickle cell disease presenting with acute complications 1
- Avoid over-reliance on screening tests alone—sickling tests and solubility tests are screening tools only and require confirmatory hemoglobin separation techniques 3
- Recognize that most patients with sickle cell disease will have been diagnosed previously, making routine electrophoresis unnecessary in known cases 1, 2
Treatment Overview After Confirmation
Once sickle cell disease is confirmed, disease-modifying therapies should be initiated:
First-Line Therapy
- Hydroxyurea remains first-line therapy for most individuals with SCD, increasing fetal hemoglobin and reducing red blood cell sickling 4, 5
Adjunctive FDA-Approved Therapies
- L-glutamine reduces acute complications and hospitalizations—in clinical trials, it reduced median sickle cell crises from 4 to 3 per year and decreased median hospital days from 11 to 6.5 days 6, 4
- Crizanlizumab reduced pain crises from 2.98 to 1.63 per year compared with placebo 4
- Voxelotor increased hemoglobin by at least 1 g/dL in 51% vs 7% with placebo 4
Transfusion Considerations
- Pre-operative transfusion should target hemoglobin around 100 g/L and reduce HbS% to <30% for high-risk surgeries 1
- Automated red cell exchange (RCE) is preferred over manual RCE or simple transfusion for chronic transfusion requirements, as it reduces iron overload risk 1
- All transfused blood must be HbS negative and matched for ABO, Rh, and Kell antigens 1, 7