Advertisement

Red Blood Cell and Serum Magnesium Levels Among Children and Adolescents With Sickle Cell Anemia

  • Osama Omar Yousif
  • Mea’ad Kadhum Hassan
  • Lamia Mustafa Al-Naama
Article
  • 71 Downloads

Abstract

Patients with sickle cell anemia (SCA) can acquire many biochemical abnormalities, including altered magnesium levels. However, the roles of magnesium in the pathogenesis and management of SCA need to be determined. The aim of this work was to evaluate magnesium levels among pediatric patients with SCA in Basra, Iraq. The study employed a case-control design and examined 87 patients with SCA (3–15 years old) who had attended the Basra Center for Hereditary Blood Diseases while in a steady state and 90 apparently healthy control subjects. Complete blood count, red blood cell (RBC), and serum magnesium, calcium, potassium, sodium, zinc, and copper levels were measured in all subjects. The results revealed significantly lower RBC and serum magnesium levels among the patients with SCA (3.62 ± 0.42 and 1.35 ± 0.19 mg/dL, respectively) than those among the control subjects (4.47 ± 0.55 and 1.87 ± 0.27 mg/dL, respectively). In addition, compared to the control subjects, the patients with SCA had significantly lower serum levels of potassium, sodium, and zinc; significantly higher serum levels of copper; and significantly higher Ca/Mg and Na/Mg ratios. Among the SCA patients, the RBC magnesium level was significantly negatively associated with the frequencies of vaso-occlusive crises (r = − 0.423, P < 0.001) and disease-related hospitalization (r = − 0.225, P < 0.05). To conclude, the RBC magnesium level, but not the serum magnesium level, is significantly associated with vaso-occlusive crises and hospitalization. Therefore, screening and management of low RBC magnesium levels in SCA patients are required.

Keywords

Magnesium Sickle cell anemia Children 

Notes

Acknowledgements

We thank Dr. Maysaa B. Al-Rudainee, family physician, Basra Health Directorate, and Dr. Assad Yehia, Professor of Animal Breeding, College of Agriculture, for their extensive assistance in conducting the statistical analysis of the data. We also thank Mrs. Sumaya S. Ali, Biochemistry Department, College of Medicine, Basra University, for her help and kind cooperation.

Authors’ Contributions

OA, MK, and LM designed and planned the study. OA collected the data and the samples, and LM performed the lab investigations. All authors contributed to the writing of the manuscript and have read and approved the final manuscript.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Ethical Approval

All procedures in studies involving human participants were performed in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

References

  1. 1.
    Driss A, Asare KO, Hibbert JM, Adamkiewicz TV, Stiles JK (2009) Sickle cell disease in the past genomic era. A monogenic disease with a polygenic phenotype. Genomic Insights 2:23–48CrossRefGoogle Scholar
  2. 2.
    Frenette PS, Atweh GF (2007) Sickle cell disease: old discoveries, new concepts, and future promise. J Clin Invest 117:850–858.  https://doi.org/10.1172/JCI30920 CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Ballas SK, Lieff S, Benjamin LJ, Dampier CD, Heeney MM, Hoppe C, Johnson CS, Rogers ZR, Smith-Whitley K, Wang WC, Telen MJ, on Behalf of the Investigators at the Comprehensive Sickle Cell Centers (2010) Definitions of the phenotypic manifestations of sickle cell disease. Am J Hematol 85:6–13.  https://doi.org/10.1002/ajh.21550 CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Hillman RS, Ault KA, Rinder HM (2005) Hemoglobinopathies. In: Hillman RS, Ault KA, Rinder HM (eds) Hematology in clinical practice. 4th edn. McGraw-Hill, Philadelphia, pp 80–94Google Scholar
  5. 5.
    Hyacinth HI, Gee BE, Hibbert JM (2010) The role of nutrition in sickle cell disease. Nutr Metab Insights 3:57–67.  https://doi.org/10.4137/NMI.S5048 CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Oladipo OO, Temiye EO, Ezeaka VC, Obomanu P (2005) Serum magnesium, phosphate and calcium in Nigerian children with sickle cell disease. West Afr. J Med 24:120–123Google Scholar
  7. 7.
    Zehtabchi S, Sinert R, Rinnert S, Chang B, Heinis C, Altura RA, Altura BT, Altura BM (2004) Serum ionized magnesium levels and ionized calcium-to-magnesium ratios in adult patients with sickle cell anemia. Am J Hematol 77:215–222.  https://doi.org/10.1002/ajh.20187 CrossRefPubMedGoogle Scholar
  8. 8.
    De Franceschi L, Bachir D, Galacteros F, Tchernia G, Cynober T, Alper S et al (1997) Oral magnesium supplements reduce erythrocyte dehydration in patients with sickle cell disease. J Clin Invest 100:1847–1852CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Brousseau DC, Scott JP, Hillary CA, Panepinto JA (2004) The effect of magnesium on length of stay for pediatric sickle cell pain crisis. Acad Emerg Med 11:968–972.  https://doi.org/10.1197/j.aem.2004.04.009 CrossRefPubMedGoogle Scholar
  10. 10.
    Hankins JS, Wynn LW, Brugnara C, Hillery CA, Li CS, Wang WC (2008) Phase I study of magnesium pidolate in combination with hydroxycarbamide for children with sickle cell anaemia. Br J Hematol 140:80–85.  https://doi.org/10.1111/j.1365-2141.2007.06884 Google Scholar
  11. 11.
    Emokpae MA, Tijani AD (2014) The impact of proteinuria on serum levels of trace elements in sickle cell disease patients. J med. Biomed Sci 3:16–20.  https://doi.org/10.4314/jmbs.v3i3.3 Google Scholar
  12. 12.
    De Franceschi L, Bachir F, Galacteros G, Tchernia T, Cynober D, Neuberg Y et al (2000) Oral magnesium pidolate: effects of long-term administration in patients with sickle cell disease. Br J Haematol 108:284–289CrossRefPubMedGoogle Scholar
  13. 13.
    Rinehart J, Gulcicek EE, Joiner CH, Lifton RP, Gallagher PG (2010) Determinants of erythrocyte hydration. Curr Opin Hematol 17:191–197.  https://doi.org/10.1097/MOH.0b013e32833800d0 PubMedPubMedCentralGoogle Scholar
  14. 14.
    Aleem A (2008) Renal abnormalities in patients with sickle cell disease. A single center report from Saudi Arabia. Saudi J Kidney Dis Transplant 19:194–199Google Scholar
  15. 15.
    Goldman RD, Mounstephen W, Kirby-Allen M, Friedman JN (2013) Intravenous magnesium sulfate for vaso-occlusive episodes in sickle cell disease. Pediatrics 132:1634–1641.  https://doi.org/10.1542/peds.2013-2065 CrossRefGoogle Scholar
  16. 16.
    Brousseau DC, Scott JP, Badaki-Makun O, Darbari DS, Chumpitazi CE, Airewele GE, Ellison AM, Smith-Whitley K, Mahajan P, Sarnaik SA, Casper TC, Cook LJ, Dean JM, Leonard J, Hulbert ML, Powell EC, Liem RI, Hickey R, Krishnamurti L, Hillery CA, Nimmer M, Panepinto JA, for the Pediatric Emergency Care Applied Research Network (PECARN) (2015) A multicenter randomized controlled trial of intravenous magnesium for sickle cell pain crisis in children. Blood 126:1651–1657.  https://doi.org/10.1182/blood-2015-05-647107 CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Ballas SK (2012) More definitions in sickle cell disease: steady state versus baseline data. Am J Hematol 87:338–339.  https://doi.org/10.1002/ajh.22259 CrossRefPubMedGoogle Scholar
  18. 18.
    Omoti CE (2005) Hematological values in sickle cell anemia in steady state and during vaso-occlusive crisis in Benin City. Nigeria Annals Afr Med 4:62–67Google Scholar
  19. 19.
    Jain D, Italia K, Sarathi V, Ghoshand K, Colah R (2012) Sickle cell anemia from central India: a retrospective analysis. Indian Pediatr 49:911–913CrossRefPubMedGoogle Scholar
  20. 20.
    Frei-Jones MJ, Field JJ, DeBaun MR (2009) Risk factors for hospital readmission within 30-days: a new quality measure for children with sickle cell disease. Pediatr Blood Cancer 52:481–485.  https://doi.org/10.1002/pbc.21854 CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Tarlakazan S, Gültekin F, Aslan SL, Heper G (1990) The effect of aminoglycosides on the serum magnesium level. Mikrobiyol Bul 24:32–40PubMedGoogle Scholar
  22. 22.
    Swaminathan R (2003) Magnesium metabolism and its disorders. Clin Biochem Rev 24:47–66PubMedPubMedCentralGoogle Scholar
  23. 23.
    Lo SF (2016) Reference intervals for laboratory tests and procedures, chapter 727. In: Kliegman RM, Stanton BF, St Geme JW III, Schor NF (eds) Nelson textbook of pediatrics, 20th edn. Elsevier, Inc., Philadelphia PA, pp 3464–3473Google Scholar
  24. 24.
    Laires MJ, Monteiro CP, Bicho M (2004) Role of cellular magnesium in health and human disease. Front Biosci 9:262–276CrossRefPubMedGoogle Scholar
  25. 25.
    Khan JAJ (2003) Vitamin D status and serum level of some elements in children with sickle cell disease in Jeddah, Saudi Arabia. Pak J Med Sci 19:295–299Google Scholar
  26. 26.
    Rivera A, Ferreira A, Bertoni D, Romero JR, Brugnara C (2005) Abnormal regulation of Mg2+ transport via Na/mg exchanger in sickle erythrocytes. Blood 105:382–386.  https://doi.org/10.1182/blood-2003-11-3755 CrossRefPubMedGoogle Scholar
  27. 27.
    Jahnen- Dechent W, basics KMM (2012) Magnesium basics. Clin Kidney 5:i3–i14.  https://doi.org/10.1093/ndtplus/sfr163 CrossRefGoogle Scholar
  28. 28.
    Nnodim JK, Samue M, Dioka CE, Onah CE, Ihim A, Atuegbu C (2014) Trace elements deficiency in patients with homozygous sickle cell disease. Br J Med Med Res 4:3878–3883.  https://doi.org/10.9734/BJMMR/2014/7489 CrossRefGoogle Scholar
  29. 29.
    De Franceschi L (2009) Pathophysiology of sickle cell disease and new drugs for the treatment. Mediterr J Hematol Infect Dis 1:e2009024.  https://doi.org/10.4084/MJHID.2009.024 PubMedPubMedCentralGoogle Scholar
  30. 30.
    Brugnara C (1995) Erythrocyte dehydration in pathophysiology and treatment of sickle cell disease. Curr Opin Hematol 2(2):132–138CrossRefPubMedGoogle Scholar
  31. 31.
    Gupta V, Singh AK, Saha J, Nigam P, Patil KSB, Singh N (2012) Variation in serum electrolyte in sickle cell patients in Chhattisgarh population. Int J Cur Sci Res 2:239–243Google Scholar
  32. 32.
    Than NN, Soe HHK, Palaniappan SK, Abas ABL, De Franceschi L (2017) Magnesium for treating sickle cell disease (Review). Cochrane Database of Systematic Reviews Issue 4. Art. No.: CD011358.  https://doi.org/10.1002/14651858.CD011358.Pub2
  33. 33.
    Pandey S, Sharma A, Dahia S, Shah V, Sharma V, Mishra RM, Pandey S, Saxena R (2012) Biochemical indicator of sickle cell disease: preliminary report from India. Ind J Clin Biochem 27:191–195.  https://doi.org/10.1007/s12291-011-0162-y CrossRefGoogle Scholar
  34. 34.
    Agoreyo FO, Nwanze N (2010) Plasma sodium and potassium changes in sickle cell patients. Int J Genet Mol Biol 2:014–019Google Scholar
  35. 35.
    Bara M, Guiet-Bara A, Durlach J (1993) Regulation of sodium and potassium pathways by magnesium in cell membranes. Manges Res 6(2):167–177Google Scholar
  36. 36.
    Nwaoguikpe RN, Braide W (2012) The antisickling effects of some micronutrients and antioxidant vitamins in sickle cell disease management. J med. Med Sci 3:334–340Google Scholar
  37. 37.
    Prasad AS (2013) Biochemistry of Zinc. Springer Science & Business Media, New York, pp 136–144Google Scholar
  38. 38.
    Maret W. (2013) Zinc and human disease. In: Sigel A., Sigel H., Sigel R. (eds) Interrelations between essential metal ions and human diseases. Metal Ions in Life Sciences, vol 13. Springer, DordrechtGoogle Scholar
  39. 39.
    Al-Naama LM, Hassan MK, Mehdi JK (2015) Association of erythrocytes antioxidant enzymes and their cofactors with markers of oxidative stress in patients with sickle cell anemia. Qatar Med J 14(1):1–10.  https://doi.org/10.5339/qmj.2015.14 Google Scholar
  40. 40.
    Hasanato RMW (2006) Zinc and antioxidant vitamin deficiency in patients with severe sickle cell anemia. Ann Saudi Med 26:17–21.  https://doi.org/10.5144/0256-4947.2006.17 CrossRefPubMedGoogle Scholar
  41. 41.
    Bot YS, Benjamin A, Nyango DY, Ventmack DT, Eunice CB, Etukudu NS et al (2013) Analyses of cu and Zn in serum of sickle cell disease patients in Jos. Afr J med. Biochemistry 1:1–4Google Scholar
  42. 42.
    Pandey S, Ranjan R, Toteja GS, Rao S, Mishra RM, Pandey SW et al (2011) Micronutrients status along with hematological and biochemical parameters in sickle subtypes: preliminary report from India. Rev Hematol Mex 12:131–137Google Scholar
  43. 43.
    Nagalla S, Ballas SK (2016) Drugs for preventing red blood cell dehydration in people with sickle cell disease. Cochrane Database of Systematic Reviews Issue 1.  https://doi.org/10.1002/14651858.CD003426.pub5,
  44. 44.
    de Baaij JHF, Hoenderop JGJ, Bindels RJM (2015) Magnesium in man: implications for health and disease. Physiol Rev 95:1–46CrossRefPubMedGoogle Scholar
  45. 45.
    Hoenderop JGJ, Bindels RJM (2005) Epithelial Ca2_ and Mg2_ channels in health and disease. J Am Soc Nephrol 16:15–26.  https://doi.org/10.1681/ASN.2004070523 CrossRefPubMedGoogle Scholar
  46. 46.
    Judd AM, Best KB, Christensen K, Rodgers GM, Bell JD (2003) Alterations in sensitivity to calcium and enzymatic hydrolysis of membranes from sickle cell disease and trait erythrocytes. Am J Hematol 72:162–169.  https://doi.org/10.1002/ajh.10281 CrossRefPubMedGoogle Scholar
  47. 47.
    Emokpae AM, Adejumo BIG (2015) Serum total calcium to magnesium ratio is higher in sickle cell disease patients with proteinuria than without proteinuria. J Adv In Biol Basic Res 1(3):83–85Google Scholar
  48. 48.
    Eaton WA, Bunn HF (2017) Treating sickle cell disease by targeting HbS polymerization. Blood 129(20):2719–2726CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Osama Omar Yousif
    • 1
  • Mea’ad Kadhum Hassan
    • 2
  • Lamia Mustafa Al-Naama
    • 3
  1. 1.Basra Pediatric Specialty Hospital, Basra Health DirectorateBasraIraq
  2. 2.Department of Pediatrics, College of MedicineUniversity of BasraBasraIraq
  3. 3.Department of Biochemistry, College of MedicineUniversity of BasraBasraIraq

Personalised recommendations