Haemoglobin crystals


Derivation: Descriptive term: haemoglobin in crystalline form within an erythrocyte


Variously described as tetragonal, hexagonal or rhomboidal crystals, but in practice highly variable shapes resembling rods, solid lumps or geometric shapes (see pathogenesis). The remainder of the cell will have reduced haemoglobin content and may have an empty (“ghost”) appearance.

Image 1. Appears as a very dense haemoglobin area, often in a distorted cell. The crystals are classically hexagonal or rhomboidal, but in practice irregular shapes and particularly rods are common. The red cell will often be hypochromic and may appear as a ghost cell as the haemoglobin is condensed into the crystal form. The crystal form of haemoglobin is seen only in the presence of excess haemoglobin C (HbCC, HbSC, HbC-beta thalassaemia) so look for evidence of other typical cell types seen in the disorder. In this case there are accompanying target cells and irregularly contracted cells.


The crystallisation process results from altered electrostatic properties of HbC caused by the loss of charge associated with the mutation– crystals therefore imply the presence of HbC. They form in homozygous HbC disease (HbCC), but may be found in HbSC and HbC/beta thalassaemia (they do not form in HbC heterozygotes).


The crystal formation will often involve a large portion of the intracellular haemoglobin leaving an empty membrane shell. For this reason, there may be confusion with a hemighost or blister cell. The key here is to recognise the cellular background (particularly frequent target cells or boat cells), but also to appreciate the appearance of crystals.


The presence of haemoglobin C
Signifies any cell where HbC is present in a significant amount: HbCC, HbSC HbC-beta thalassaemia
Not HbC trait

Clinical Examples

Clinical Image 1 The most obvious example has two rounded crystals within an empty “ghost” erythrocyte. The surrounding cells are dominated by contracted forms and target cells – some of which have rather dense and rectangular-looking “bulls eyes” (bottom centre of image). Clinical condition HbCC.

Clinical Image 2 The clearest crystal present is in an elongated cell that has a boat-like form and contains a long central rod-shaped crystal. Note also the elongated cell (upper left) in which the haemoglobin is contracted to the two opposing poles of the cell. Clinical condition HbCC.

Clinical Image 3 A further elongated boat-shaped cell with a central “rod”. Clinical condition HbCC.

Clinical Image 4. A ghost (empty) erythrocyte has a single condensed crystal of haemoglobin within it (lower centre of film). A second erythrocyte (lower right quadrant) has a central square of condensed haemoglobin crystal. Clinical condition HbCC


In HbC, glutamic acid in the sixth position of the β-globin chain is replaced by lysine. This amino acid substitution alters the electrostatic interactions of the haemoglobin molecule leading to decreased solubility in its de-oxygenated (or hypertonic/dehydrated) state causing crystal formation. Impurities (other red cell proteins and denatured haemoglobin) are incorporated into the crystals and severely affect their growth so that perfect crystals tend not to form in these conditions: although often described as hexagonal or rhomboidal, very irregular or rod-like crystals are often seen.