What is the significance of a negative protein electrophoresis result in diagnosing and managing sickle cell disease?

From the Guidelines

A negative protein electrophoresis result in sickle cell disease indicates the absence of hemoglobin S (HbS), which essentially rules out sickle cell disease as a diagnosis, with a negative predictive value of 100%. This finding is significant because sickle cell disease is characterized by the presence of abnormal hemoglobin S, which causes red blood cells to become rigid and sickle-shaped. When protein electrophoresis shows normal hemoglobin patterns (predominantly hemoglobin A in adults) without HbS bands, clinicians must consider alternative diagnoses for a patient's symptoms. For patients already diagnosed with sickle cell disease who are receiving treatments like hydroxyurea, exchange transfusions, or newer therapies like voxelotor or crizanlizumab, a negative result might indicate successful treatment that has significantly reduced the proportion of sickle hemoglobin. However, this is uncommon as these treatments typically reduce complications rather than eliminate HbS entirely. In patients who have undergone hematopoietic stem cell transplantation, a negative result could confirm successful engraftment and cure. The basic science behind this involves the separation of proteins based on their electrical charge during electrophoresis, allowing visualization of different hemoglobin variants. A negative result should prompt verification with more specific tests like high-performance liquid chromatography (HPLC) or hemoglobin solubility testing to confirm the absence of HbS.

Some key points to consider:

• The absence of HbS on protein electrophoresis is a strong indicator that the patient does not have sickle cell disease 1.
• Alternative diagnoses should be considered in patients with symptoms suggestive of sickle cell disease but a negative protein electrophoresis result.
• Treatments for sickle cell disease, such as hydroxyurea and exchange transfusions, can reduce the proportion of sickle hemoglobin, but a negative result is uncommon 1.
• Hematopoietic stem cell transplantation can cure sickle cell disease, and a negative protein electrophoresis result can confirm successful engraftment 1.
• Verification of a negative result with more specific tests, such as HPLC or hemoglobin solubility testing, is necessary to confirm the absence of HbS 1.

From the Research

Negative Predictive Value of Protein Electrophoresis for Sickle Cell Patients

• The negative predictive value of protein electrophoresis for sickle cell patients is not directly mentioned in the provided studies 2, 3, 4, 5, 6.
• However, protein electrophoresis is a diagnostic tool used to identify abnormal hemoglobin variants, such as sickle hemoglobin (Hb S) 3.
• A negative result on protein electrophoresis would suggest that the patient does not have sickle cell disease, but it does not rule out other hemoglobinopathies or related conditions.
• The significance of a negative protein electrophoresis result in diagnosing and managing sickle cell disease is that it can help to exclude sickle cell disease as a diagnosis, but further testing and evaluation may be necessary to determine the underlying cause of symptoms or to diagnose other related conditions 3, 6.

Diagnostic Considerations

• Sickle cell disease is typically diagnosed through newborn screening programs or when patients present with unexplained severe atraumatic pain or normocytic anemia 3.
• Protein electrophoresis is one of the diagnostic tools used to confirm the presence of sickle hemoglobin (Hb S) 3.
• Other diagnostic considerations include complete blood counts, reticulocyte counts, and hemoglobin fractionation 2, 5.

Management and Treatment

• The management and treatment of sickle cell disease typically involve a multidisciplinary approach, including pain management, blood transfusions, and disease-modifying therapies such as hydroxyurea 2, 3, 4, 5, 6.
• Hydroxyurea has been shown to reduce the frequency of painful crises and blood transfusions in patients with sickle cell disease 4, 5.
• Blood transfusions may be used to increase tissue delivery of oxygen and to reduce the risk of complications such as stroke and acute chest syndrome 2, 6.