Methods for hemoglobin analysis and hemoglobinopathy testing
- Carolyn Hoppe, MD
Carolyn Hoppe, MD
- Associate Hematologist/Oncologist, UCSF Benioff Children's Hospital Oakland
- Associate Scientist, Children's Hospital Oakland Research Institute
- Director, Hemoglobinopathy Reference Laboratory
Hemoglobinopathies are inherited disorders in which a genetic abnormality affects the amount or structure of one or more of the globin chains in hemoglobin (Hb), the major oxygen transport protein in red blood cells (RBCs). The most common hemoglobinopathies such as thalassemia and sickle cell disease (SCD) are relatively straightforward to diagnose. However, there are thousands of other genetic abnormalities in the globin genes, the majority of which are clinically silent; for many of these, characterizing the abnormality and its clinical implications is more challenging. It is important to identify clinically significant hemoglobinopathies causing SCD and thalassemia to inform optimal management in affected individuals and to offer genetic counseling and reproductive options in carriers.
This topic reviews methods for hemoglobinopathy testing and their appropriate use. Additional information about the diagnosis of specific disorders and an overview of prenatal hemoglobinopathy testing are presented separately:
●Sickle cell trait and SCD – (See "Diagnosis of sickle cell disorders".)
●Alpha and beta thalassemias – (See "Clinical manifestations and diagnosis of the thalassemias".)
●Unstable hemoglobin variants – (See "Unstable hemoglobin variants".)
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- HEMOGLOBIN BIOLOGY
- Normal hemoglobins
- Types of abnormalities
- AVAILABLE TESTING METHODS
- Overview of methods
- Protein chemistry methods
- - Overview of protein chemistry methods
- - HPLC
- - Isoelectric focusing
- - Capillary electrophoresis
- - Gel electrophoresis
- Molecular (DNA-based) methods
- - Overview of DNA-based methods
- - Traditional DNA sequencing and allele-specific PCR
- - Gap-PCR and MLPA
- - Array CGH
- - NGS
- Point-of-care assays
- Other disease-specific tests
- - Sickle cell prep
- - Heinz body prep
- - Hb H staining
- INITIAL EVALUATION
- Indications for hemoglobin analysis
- Overview of approach
- Clues from the CBC
- Common clinical scenarios
- - Population screening (eg, routine newborn screen)
- - Prenatal testing
- - Patient with suspected sickle cell disorder
- - Patient with suspected thalassemia
- - Patient with unknown variant
- REFERRAL TO A SPECIALIZED LABORATORY
- SUMMARY AND RECOMMENDATIONS