Hemoglobin H inclusion bodies in RBCs stained with brilliant cresyl blue

Peripheral blood stained with BCB reveals Hb H inclusion bodies; Hb H is a tetramer of beta globin chains.

• Hb H staining is a simple, useful screening test for alpha thalassemia Hb H disease in limited resource regions. The severity of the alpha thalassemia syndrome correlates with the number of cells with inclusions.
• This patient had ATRX syndrome (alpha thalassemia X-linked intellectual disability), due to variation in the ATRX gene.
• The tetramers are usually soluble and therefore are rarely seen with standard May–Grünwald–Giemsa stain. However, the tetramers are unstable and precipitate when exposed to an oxidizing agent such as BCB.
• The inclusions are concentrated just below the RBC membrane and push the membrane outward. Under microscopic examination they give the appearance of being outside the cell, leading to the name "golf ball cells."
• The inclusions damage the RBC membrane and induce hemolysis.