Haemoglobin Bart’s Hydrops Fetalis

Haemoglobin Bart’s comprises a tetramer of γ globin chains (γ₄). It results from a four gene α deletion. It has an extremely high oxygen affinity and is unstable, precipitating in red blood cells. This results in membrane damage and markedly reduced red cell survival.

Haemoglobin Bart’s hydrops fetalis describes the severe anaemia, extramedullary haematopoiesis, hypoalbuminaemia and oedema which causes stillbirth or early neonatal death in affected neonates.

Blood film from a fetal blood sample. The fetus was diagnosed with Hb Bart’s hydrops fetalis.

Blood film from a newborn with Hb Bart’s hydrops fetalis.

Blood film features:

• Severe hypochromic, microcytic anemia
• Marked poikilocytosis
• Numerous circulating nRBCs

Differential diagnosis:

• ß thalassaemia major (at birth, the phenotype of ß thalassaemia major is ameliorated by increased Hb F).
• Hereditary pyropoikilocytosis (cells are normocytic and haemoglobinisation is normal).
• Congenital dyserythropoietic anaemias (often characterised by macrocytosis with no reticulocytosis).

Haemoglobin electrophoresis:

Alkaline gel electrophoresis from a newborn with Hb Bart’s hydrops fetalis. There is no normal haemoglobin A or haemoglobin F band (normal alpha chains are required for the synthesis of both). Instead, there is a fast band corresponding to Hb Bart’s.

HPLC:

HPLC from a newborn with Hb Bart’s hydrops fetalis. There is no normal haemoglobin A. There is a variant haemoglobin with an extremely short retention time (red arrow), corresponding to haemoglobin Bart’s.

Other resources:

• PHE Family Origin Questionnaire
• PHE Sickle Cell and Thalassaemia Screening Programme (2019)
• BCSH Guideline: Significant Haemoglobinopathies: Guidelines for Screening and Diagnosis (2010)