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A comprehensive review of hydroxyurea for beta-haemoglobinopathies: the role revisited during COVID-19 pandemic #MMPMID33648529
Yasara N; Premawardhena A; Mettananda S
Orphanet J Rare Dis 2021[Mar]; 16 (1): 114 PMID33648529show ga
BACKGROUND: Hydroxyurea is one of the earliest drugs that showed promise in the management of haemoglobinopathies that include beta-thalassaemia and sickle cell disease. Despite this, many aspects of hydroxyurea are either unknown or understudied; specifically, its usefulness in beta-thalassaemia major and haemoglobin E beta-thalassaemia is unclear. However, during COVID-19 pandemic, it has become a valuable adjunct to transfusion therapy in patients with beta-haemoglobinopathies. In this review, we aim to explore the available in vitro and in vivo mechanistic data and the clinical utility of hydroxyurea in beta-haemoglobinopathies with a special emphasis on its usefulness during the COVID-19 pandemic. MAIN BODY: Hydroxyurea is an S-phase-specific drug that reversibly inhibits ribonucleoside diphosphate reductase enzyme which catalyses an essential step in the DNA biosynthesis. In human erythroid cells, it induces the expression of gamma-globin, a fetal globin gene that is suppressed after birth. Through several molecular pathways described in this review, hydroxyurea exerts many favourable effects on the haemoglobin content, red blood cell indices, ineffective erythropoiesis, and blood rheology in patients with beta-haemoglobinopathies. Currently, it is recommended for sickle cell disease and non-transfusion dependent beta-thalassaemia. A number of clinical trials are ongoing to evaluate its usefulness in transfusion dependent beta-thalassaemia. During the COVID-19 pandemic, it was widely used as an adjunct to transfusion therapy due to limitations in the availability of blood and logistical disturbances. Thus, it has become clear that hydroxyurea could play a remarkable role in reducing transfusion requirements of patients with haemoglobinopathies, especially when donor blood is a limited resource. CONCLUSION: Hydroxyurea is a well-tolerated oral drug which has been in use for many decades. Through its actions of reversible inhibition of ribonucleoside diphosphate reductase enzyme and fetal haemoglobin induction, it exerts many favourable effects on patients with beta-haemoglobinopathies. It is currently approved for the treatment of sickle cell disease and non-transfusion dependent beta-thalassaemia. Also, there are various observations to suggest that hydroxyurea is an important adjunct in the treatment of transfusion dependent beta-thalassaemia which should be confirmed by randomised clinical trials.
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Orphanet+J+Rare+Dis 2021 ; 16 (1): 114
