Abstract
Background and Objectives: Vaso-occlusive crisis, a common clinical presentation of sickle cell disease is a major cause of morbidity. It has been observed in some cases of sickle cell trait also. Hydroxyurea exerts beneficial effect primarily by increasing fetal hemoglobin and also through other mechanisms. The Arabian-Indian haplotype of Hemoglobin S is associated with moderate form of disease and high fetal hemoglobin level. This study was conducted to assess the clinical and hematological response of homozygous and heterozygous cases of Hemoglobin S to hydroxyurea therapy. The adverse reactions to the drug were also observed.
Material and Methods: The study, an interventional case series, was conducted at a teaching hospital in Central India during January 2013 to December 2014.A total of 54 cases satisfying eligibility criteria were recruited. 9 cases (2 due to severe reaction and 7 due to poor compliance) were excluded. Thus study comprised of 45 cases of sickle cell disease (36 homozygous and 9 heterozygous). Detailed clinical examination, baseline investigations and HPLC were performed. Cases received 10 mg/kg/ day of Hydroxyurea and were followed up weekly in sickle-cell opd for compliance, effectiveness and adverse reactions. At the end of one year of hydroxyurea therapy, baseline investigations and HPLC were repeated. Appropriate statistical analysis was done using STATA version 13.1.
Results: Statistically significant clinical response, namely decrease in the frequency of vaso-occlusive crises and duration of hospitalization and improvement of clinical score was observed (p<0.0001)in homozygous and heterozygous cases of sickle cell disease. Statistically significant hematological response (p<0.0001) namely, increase in hemoglobin, mean corpuscular volume of red cell and fetal hemoglobin level, decrease in total leukocyte count was observed in homozygous and heterozygous cases of sickle cell disease. Hydroxyurea was well tolerated.
Conclusion: Hydroxyurea is effective in homozygous cases of sickle cell disease. Hydroxyurea is effective in HPLC proven heterozygous cases of sickle cell; however, detailed hemoglobin structure and genetic studies recruiting larger number of these cases is recommended. Hydroxyurea is effective despite high level of fetal hemoglobin. Hydroxyurea is well tolerated and must be administered with regular monitoring.
Keywords: Sickle cell disease (SS), sickle cell trait (AS), hydroxyurea, fetal hemoglobin, clinical response, hematological response, adverse reactions.
References
- Wang WC: Sickle cell anemia and other sickling syndromes. In: Greer JP, Rodgers GM, Foerster J, Paraskevas F, Lukens JN, Glader B, editors. Wintrobe’s Clinical Haematology. Philadelphia: Lippincott Williams and Wilkins A Wolters Kluver company; 2004:1263-1311
- Kar BC.Sickle cell disease in India. J Assoc Physicians India 1991;39(12):954-960
- Powars DR, Chan L, Schroeder WA. The influence of fetal haemoglobin on the clinical expression of sickle cell anemia. Ann N Y Acad Sci.1989;565:262-278
- Charache S, Terrin ML, Moore RD et al .Effect of hydroxyurea on the frequency of painful crisis in sickle cell anemia.I nvestigators of the multicentre study of hydrxyurea in sickle cell anemia. N Engl J Med 1995;332:1317-1322
- Steinberg MH, Nagwl RL, Brugnara C. Cellular effects of hydroxyurea in HbSC disease. British Journal of Hematology; 1997:838-844
- Patel S, Purohit P, Mashon RS et al. The effect of hydroxyurea on compound heterozygotes for sickle cell hemoglobin D Punjab-A single centre experience in eastern India. pediatric blood and cancer2014;61(8):1341-1346
- Al-Jama AH, Al-Dabbous IA et al. Hydroxyurea in sickle cell disease patients from Eastern Saudi Arabia. Saudi Med J 2002;23(3):277-281
- Surve RR, Mukherjee MB, Kate SL et al. Detection of beta S gene: an evaluation of the solubility test against automated chromatography and hemoglobin electrophoresis. Br J Biomed Sci 2000;57:292-294
- Italia K, Jain D, Gattani S et al. Hydoxyurea in sickle cell disease-a study of clinico-pharmacological efficacy in the Indian haplotype. Blood Cell, Molecules and Disease 2008;42(1):25-31
- Steinberg MH et al: Sickle cell disease and other hemoglobinopathies. In: Lee Goldman, Andrew Schafer, editors. Cecil Medicine. Philadelphia: Elsevier Saunders; 2012. Chapter 166;1066-1074
- Charache S. Mechanism of action of hydroxyurea in the management of sickle cell anemia in adults. Semin Hematol 1997;34(Suppl.3):15-21
- Ballas SK, Dover GJ, Charache S. Effect of hydroxyurea on the rheological properties of sickle erythrocytes in vivo. Am J Hematol 1989;32:104-111
- Russell E. Ware, Banu Aygun. Advances in the use of Hydroxyurea. Hematology 2009;34:62-69
- Patel DK, Mashon RS, Patel S et al.Low dose Hydroxyurea is effective in reducing the incidence of painful crisis and frequency of blood transfusion insickle cell anemia patients from eastern India. Hemoglobin; 2012.vol.36:409-420
- Singh H, Dulhani N, Kumar BN et al. Effective control of sickle cell disease with hydroxyureatherapy. Indian J Pharmacology 2010;42(1):32-35
- Colah RB, Mukherjee M, Ghosh K. Sickle cell disease in India. Curropin Hematol 2014;21(3):215-223
- Colah RB, Mukherjee M, Ghosh K, Snehal M. Sickle cell disease in tribal populations in India. Indian J Med Res 2015;141(5):509-515
- Yates AM, Dedeken L, Smeltzer MP et al. Hydroxyurea treatment of children with Hemoglobin SC disease. Pediatric Blood Cancer 2013;60(2):323-325
- Miller MK, Zimmerman SA, Schultz WH, Ware RE et al.Hydroxyurea therapy for pediatric patients with haemoglobin SC disease. J Pediatric Hemat Oncol 2001;23(5):306-313
- Ballas SK, Singh P Adams-Graves P et al. Idiosyncratic side effects of Hydoxyurea in patients with sickle cell anemia. J Blood Disorders and Transfusion 2013;4:162-165.
Corresponding Author
Dr Mrinalini Hardas
Assistant Professor, Dept.of. Medicine IGGMC, Nagpur, India
DOI: https://dx.doi.org/10.18535/jmscr/v7i8.74
