Hemoglobin Patterns with Positive Sickle Solubility Test
Both hemoglobin patterns AS and SS (option E) will have a positive sickle solubility (dithionite) test because both contain hemoglobin S, which is detected by this test regardless of whether it's present in heterozygous or homozygous form.
Understanding the Sickle Solubility Test
The sickle solubility (dithionite) test is designed to detect the presence of hemoglobin S (HbS) in blood samples. This test works based on the following principles:
- It detects the presence of HbS by causing insoluble polymers to form when HbS is deoxygenated
- The test is positive whenever HbS is present, regardless of the amount
- It cannot differentiate between heterozygous (AS) and homozygous (SS) states 1
Analysis of Hemoglobin Patterns
Let's analyze each hemoglobin pattern in the question:
Positive Sickle Solubility Test:
- AS (Sickle Cell Trait): Contains 55-65% HbA and 30-40% HbS 2. The presence of HbS, even in heterozygous form, will produce a positive solubility test.
- SS (Sickle Cell Disease): Contains 80-95% HbS 1. The high concentration of HbS will definitely produce a positive solubility test.
Negative Sickle Solubility Test:
- AA (Normal): Contains 95-98% HbA with no HbS 1. Without HbS, the solubility test will be negative.
- AC: Contains HbA and HbC, but no HbS. The solubility test specifically detects HbS, not other hemoglobin variants like HbC.
Clinical Implications
The sickle solubility test has important limitations that clinicians should be aware of:
- It should not be used in isolation for diagnosis as it cannot differentiate between sickle cell trait (AS) and sickle cell disease (SS) 1
- False negative results can occur in:
- Neonates (due to high HbF levels)
- Heavily transfused patients (dilution of HbS)
- False positive results are rare but can occur in conditions like polycythemia 3
Diagnostic Algorithm
For proper hemoglobinopathy diagnosis:
- Initial screening: Sickle solubility test to detect presence of HbS
- Confirmation: If positive, proceed to definitive testing:
- Hemoglobin electrophoresis
- High-performance liquid chromatography (HPLC)
- Capillary electrophoresis
- Mass spectrometry
These confirmatory tests can differentiate between heterozygous (AS) and homozygous (SS) states, as well as identify other hemoglobin variants that may be present 1.