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When hemoglobin S (HbS) has been detected using a primary screening method, it is then crucial to determine if the HbS is homozygous, heterozygous, or is another variant. Additional procedures that may be needed include isoelectric focusing (IEF) or high performance liquid chromatography (HPLC).

Observation of RBC morphology and use of sickle cell screening may provide initial information for this diagnosis, but may be negative in some sickle cell disorders.

Polymerized chain reaction (PCR) methods are being used in prenatal diagnosis of sickle cell disorders.