Low dose oral hydroxyurea prophylaxis improves all clinico: haematological parameters among sickle cell disease patients

Butungeshwar Pradhan, Bipin K. Kullu, Sagnika Tripathy, Nayan K. Patel


Background: Sickle cell disease (SCD) an inheritable disorder of haemoglobin structure resulting from substitution of valine for glutamic acid at 6th position of β-globin chain of haemoglobin(HbS), which polymerizes on deoxygenation and undergoes to sickle shaped RBC causing vaso-occlusive painful crisis, chronic haemolysis, anaemia, frequent blood transfusions, frequent hospitalizations with increased morbidity and acute chest syndrome leading to mortalities. Presence of foetal haemoglobin (HbF) prevent sickling and use of drugs like Hydroxyurea (HU) results in increased production of HbF to prevent complications of SCD. Aims and objectives was to know the various effect of low dose HU on clinical and haematological parameters among SCD patients.

Methods: Total 100 S HbSS patients were consecutively selected, with indication for HU in 10mg/kg + 5mg folic acid/day. Baseline haemoglobin, HbF, HbS, haematocrit (HCT), TRBC, MCV, MCH, MCHC, and HbS, TPC, TWBCs, ANCs and other relevant tests as needed. Follow up haematological tests were done at 1 month and then every 3 month up to 24 months with monitoring of clinical status, hepatic, renal, and myelotoxicities. Data were collected and analyzed.

Results: There were 31 paediatric cases with mean age of 8.47±4.1 years and 69 adults with mean age of 25.9±8.2 years presented with or history of various complications. HU improves all clinical and haematological parameters significantly (Hb, HCT, HbF, MCV, MCH, MCHC,) with mild myelotoxicities (decreased ANC, TPC, WBCs).

Conclusions: HU improves all clinical and haematological parameters with mild myelotoxicities among SCD patients.


Clinical, Hydroxyurea, Haematological, Parameters, Sickle cell disease

Full Text:



Italia K, Jain D, Gattani S, Jijina F, Nadkarni A, Sawant P, et al. Hydroxyurea in sickle cell disease-a study of clinico-pharmacological efficacy in the Indian haplotype. Blood Cells, Molecules, and Diseases. 2009 Jan 1;42(1):25-31.

Balgir R. Epidemiology, population health, Genetics and phenotypic Diversity of sickle cell disease in India. Internet J Biological Anthropol. 2007;1(2).

Weatheral DJ. The inherited disease of haemoglobin are an emerging global health burden. Blood. 2010;115(22);4331-6.

Steinberg MH. Sickle cell disease: basic principles and clinical practice. Embury SH, Hebbel RP, Mohandas N, editors. New York:Raven Press; 1994 Jan.

Eaton WA, J Hofrichter. Sickle cell haemoglobin polymerization. Adv Protein Chem. 1990;40:63-279.

Ferrone F, Nagel RL. Sickle cell haemoglobin polymerization, in Disorders of haemoglobin: Genetics, pathophysiology, clinical management. F.B. Steinberg MH. Higgs D, Nagel RL. Editor. 2000;Cambridge University Press.

Mashon RS, Dash PM, Khalkho J, Dash L, Mohanty PK, Patel S, et al. Higher fetal hemoglobin concentration in patients with sickle cell disease in eastern India reduces frequency of painful crisis. European J haematology. 2009 Oct 1;83(4):383-4.

Lanzkron S, Strouse JJ, Wilson R, Beach MC, Haywood C, Park H, et al. Systematic review: hydroxyurea for the treatment of adults with sickle cell disease. Annals of internal medicine. 2008 Jun 17;148(12):939-55.

Kinney TR, Helms RW, O’Branski EE, Ohene-Frempong K, Wang W, Daeschner C, et al. Safety of hydroxyurea in children with sickle cell anemia: results of the HUG-KIDS study, a phase I/II trial. Blood. 1999 Sep 1;94(5):1550-4.

Zimmerman SA, Schultz WH, Davis JS, Pickens CV, Mortier NA, Howard TA, et al. Sustained long-term hematologic efficacy of hydroxyurea at maximum tolerated dose in children with sickle cell disease. Blood. 2004 Mar 15;103(6):2039-45.

Ferster A, Vermylen C, Cornu G, Buyse M, Corazza F, Devalck C, et al. Hydroxyurea for treatment of severe sickle cell anemia: a pediatric clinical trial. Blood. 1996 Sep 15;88(6):1960-4.

Ferster A, Tahriri P, Vermylen C, Sturbois G, Corazza F, Fondu P, et al. Five years of experience with hydroxyurea in children and young adults with sickle cell disease. Blood. 2001 Jun 1;97(11):3628-32.

Ware RE. Summary of the evidences regarding efficacy of Hydroxyurea treatment for sickle cell disease in children and adolescents. An NIH consensus Development conference held at the William H. Natcher conference centre. National Institutes of Health. Bethesda. MD.USA. 2008;29-32.

Friedrisch JR, Prá D, Maluf SW, Bittar CM, Mergener M, Pollo T, et al. DNA damage in blood leukocytes of individuals with sickle cell disease treated with hydroxyurea. Mutation Research/Genetic Toxicology and Environmental Mutagenesis. 2008 Jan 8;649(1):213-20.

Griss A. Effect of Hydroxyurea on sperm counts, motility and morphology in adult men with sickle cell or myeloproliferative disease. Intern Med J. 2007;37(3);190-2.

Berthaut I, Guignedoux G, Kirsch-Noir F, de Larouziere V, Ravel C, Bachir D, et al. Influence of sickle cell disease and treatment with hydroxyurea on sperm parameters and fertility of human males. Haematologica. 2008 Jul 1;93(7):988-93.

Charache S, Dover GJ, Moore RD, Eckert S, Ballas SK, Koshy M, et al. Hydroxyurea: effects on hemoglobin F production in patients with sickle cell anemia. Blood. 1992 May 15;79(10):2555-65.

Charache S, Terrin ML, Moore RD, Dover GJ, Barton FB, Eckert SV, et al. Effect of hydroxyurea on the frequency of painful crises in sickle cell anemia. New England J Medicine. 1995 May 18;332(20):1317-22.

Charache S, Barton FB, Moore RD, Terrin ML, Steinberg MH, Dover GJ, et al. Hydroxyurea and sickle cell anemia. Medicine. 1996 Dec 1;75(6):300-26.

Braga LB, Ferreira AC, Guimarães M, Nazário C, Pacheco P, Miranda A, et al. Clinical and laboratory effects of hydroxyurea in children and adolescents with sickle cell anemia: a Portuguese hospital study. Hemoglobin. 2005 Jan 1;29(3):171-80.

Robert PF, Anuradha A, Chris C, Stanley DW, Oswaldo C. Hydroxyurea treatment of sickle cell anaemia in hospital-based practice. Am J Hematol. 2002;70:326-8.

Patel DK, Mashon RS, Patel S, Das BS, Purohit P, Biswal SC. Low dose Hydroxyurea is effective in reducing the incidence of painful crisis and frequency of blood transfusion in sickle cell anaemia patients from eastern India. Hemoglobin. 2012;36(5):409-20.

Singh H, Dulhani N, Kumar BN, Singh P, Tiwari P. Effective control of sickle cell disease with Hydroxyurea therapy. Indian J Pharmacol. 2010;42(1):32-5.

Rigano P, De Franceschi L, Sainati L, Piga A, Piel FB, Cappellini MD, et al. Real-life experience with hydroxyurea in sickle cell disease: A multicenter study in a cohort of patients with heterogeneous descent. Blood Cells, Molecules, and Diseases. 2017:89-90.