HBH

HbH refers to an abnormal form of hemoglobin and to the related clinical condition HbH disease, a type of alpha-thalassemia. It arises when alpha-globin production is markedly reduced, most commonly due to three of the four alpha-globin genes being deleted. The unpaired beta-globin chains then form tetramers (beta4) known as HbH.

HbH tetramers are unstable and have a high oxygen affinity, meaning they bind oxygen poorly released to tissues. They tend to precipitate in red blood cells, leading to cell damage and hemolysis. In the blood, HbH can form characteristic inclusions visible in supravital stains, known as HbH bodies, and peripheral smears often show microcytosis with target cells and other signs of hemolysis. The clinical presentation ranges from mild to moderate chronic hemolytic anemia, with pallor, fatigue, splenomegaly, jaundice, and occasional crises triggered by infection or oxidant stress.

Diagnosis is based on hemoglobin analysis (electrophoresis or HPLC) showing HbH in the absence or reduction of normal HbA, supported by the detection of HbH inclusions in red cells. Genetic testing confirms deletion of alpha-globin genes. Management is supportive: folic acid supplementation, monitoring and treatment of anemia, and transfusions as needed. Iron overload from transfusions may require chelation therapy. Splenectomy is considered in selected patients with significant splenomegaly or hemolysis. Avoidance of oxidant drugs and other stressors is advised.

HbH disease is inherited in an autosomal recessive pattern, most common in populations with a high carrier rate for alpha-thalassemia. The prognosis varies with severity and access to appropriate care.