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Association of plasma homocysteine level with vaso-occlusive crisis in sickle cell anemia patients of Odisha, India

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Abstract

Vascular complications of sickle cell anemia (SCA) are influenced by many factors. Elevated plasma homocysteine (Hcy) is supposed to be an independent risk factor and is either genetic or nutritional origin. The present study evaluated the plasma Hcy level, MTHFR C677T gene polymorphism, effect of folic acid (FA) supplementation‚ and hemato-biochemical parameters in SCA and their effect on the vaso-occlusive crisis (VOC) in SCA patients of an Asian-Indian haplotype population. One hundred twenty cases of SCA (HbSS) and 50 controls with normal hemoglobin(HbAA) were studied. It was found that the plasma Hcy level is significantly higher (p < 0.0001) in patients with SCA (22.41 ± 7.8 μmol/L) compared to controls (13.2 ± 4.4 μmol/L). Moreover, patients without FA supplementation had a significantly (p < 0.001) higher Hcy level (27 ± 7 μmol/L) compared to those with supplementation (17.75 ± 5.7 μmol/L). Turkey-Kramer multiple comparison tests show that there is a significant difference (p < 0.05) in HbF percent, hemoglobin (Hb), platelet count, serum bilirubin (direct:Bil-D and total:Bil-T), aspartate transaminase (AST), lactate dehydrogenase (LDH), and plasma Hcy levels between mild and severe VOC. Between moderate VOC and severe VOC, there was a significant difference (p < 0.05) in HbF%, Bil-D, AST, Hcy. Pearson correlation revealed that plasma Hcy had a significantly (p < 0.05) positive correlation with AST, serum bilirubin (indirect and total), LDH, jaundice, stroke, VOC per year, and hospitalization per year whereas it was inversely correlated with HbF percentage, Hb level, and FA treatment. In the study population, increased plasma Hcy level, hemolysis, and platelet activation were found to influence VOC in SCA.

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Acknowledgments

We thank Prof. Manoj Kumar Mohapatra (Dean & Principal) and Director, V.S.S. Institute of Medical Sciences & Research, Burla, Sambalpur, Odisha, for permitting us to carry out this study. SM expresses his gratitude to the Hon’ble Vice Chancellor, Fakir Mohan University, for supporting the research work.

Funding

The Odisha Sickle Cell Project, National Health Mission, Odisha, provided funding support.

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Authors and Affiliations

  1. Sickle Cell Clinic and Molecular Biology Laboratory, Odisha Sickle Cell Project (NHM), Veer Surendra Sai Institute of Medical Science and Research (VIMSAR), Burla, Sambalpur, Odisha, India

    Satyabrata Meher, Siris Patel, Kishalaya Das, Snehadhini Dehury & Pradeep Kumar Mohanty

  2. Department of Medicine, Veer Surendra Sai Institute of Medical Science & Research (VIMSAR), Burla, Sambalpur, Odisha, India

    Mahendra M. Maske & Pradeep Kumar Mohanty

  3. Department of Bioscience and Biotechnology, Fakir Mohan University, Balasore, Odisha, India

    Satyabrata Meher & Bisnu Prasad Dash

  4. School of Life Sciences, Sambalpur University, Jyoti Vihar, Burla, Sambalpur, Odisha, India

    Bimal Prasad Jit

  5. Department of Cardiology, Govt. Medical College and Super Specialty Hospital, Nagpur, Maharashtra, India

    Mahendra M. Maske

  6. School of Life Sciences, AIPH University, Bhubaneswar, Odisha, India

    Padmalaya Das

  7. Head of the Department of Medicine and Project Coordinator, Odisha Sickle Cell Project (NHM), Veer Surendra Sai Institute of Medical Science and Research (VIMSAR), 3R/25, Doctor’s colony, Burla, Sambalpur, Odisha, 768017, India

    Pradeep Kumar Mohanty

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  1. Satyabrata Meher
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Contributions

Conceptualization and design: SM, BPD, and PKM. Data collection: SM, SP, KD, SD, BPJ, MMM. Laboratory work: SM. Data analysis and interpretation: SM, SP, PD, BPD, PKM. Manuscript writing: all authors. Final approval of manuscript: all authors.

Corresponding authors

Correspondence to Bisnu Prasad Dash or Pradeep Kumar Mohanty.

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Ethical approval

All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional ethical committee of VIMSAR, Burla, Odisha (VIREC-No.2016/I-F-CT-01/008) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed written consent was obtained from all individual participants included in the study.

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The authors declare that they have no financial relationship with the organization that sponsored for the research work. The funding agencies had no involvement in study design, data collection, data analysis, and data interpretation.

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Supplementary Table 4

Alleles and genotype frequency (%) of MTHFR C677T in SCA and control (DOCX 11 kb)

Supplementary Table 5

Association between the clinical presentation of SCA and MTHFR C677T genotype (DOCX 12 kb)

Supplementary Figure 1

Mutation detection by gel documentation for MTHFR (677 C > T) (PNG 1037 kb)

High resolution image (TIF 748 kb)

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Meher, S., Patel, S., Das, K. et al. Association of plasma homocysteine level with vaso-occlusive crisis in sickle cell anemia patients of Odisha, India. Ann Hematol 98, 2257–2265 (2019). https://doi.org/10.1007/s00277-019-03776-x

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