Annals of Hematology

, Volume 98, Issue 10, pp 2257–2265 | Cite as

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

  • Satyabrata Meher
  • Siris Patel
  • Kishalaya Das
  • Snehadhini Dehury
  • Bimal Prasad Jit
  • Mahendra M. Maske
  • Padmalaya Das
  • Bisnu Prasad DashEmail author
  • Pradeep Kumar MohantyEmail author
Original Article


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.


Sickle cell anemia Homocysteine Folic acid Vaso-occlusive crisis Hemolysis Methyltetrahydrofolate reductase 



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.

Author 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.

Funding information

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

Compliance with ethical standards

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.

Informed consent

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

Financial relationship

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.

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

277_2019_3776_MOESM1_ESM.docx (12 kb)
Supplementary Table 4 Alleles and genotype frequency (%) of MTHFR C677T in SCA and control (DOCX 11 kb)
277_2019_3776_MOESM2_ESM.docx (13 kb)
Supplementary Table 5 Association between the clinical presentation of SCA and MTHFR C677T genotype (DOCX 12 kb)
277_2019_3776_Fig2_ESM.png (1 mb)
Supplementary Figure 1

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

277_2019_3776_MOESM3_ESM.tif (749 kb)
High resolution image (TIF 748 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Satyabrata Meher
    • 1
    • 3
  • Siris Patel
    • 1
  • Kishalaya Das
    • 1
  • Snehadhini Dehury
    • 1
  • Bimal Prasad Jit
    • 4
  • Mahendra M. Maske
    • 2
    • 5
  • Padmalaya Das
    • 6
  • Bisnu Prasad Dash
    • 3
    Email author
  • Pradeep Kumar Mohanty
    • 1
    • 2
    • 7
    Email author
  1. 1.Sickle Cell Clinic and Molecular Biology Laboratory, Odisha Sickle Cell Project (NHM)Veer Surendra Sai Institute of Medical Science and Research (VIMSAR)SambalpurIndia
  2. 2.Department of MedicineVeer Surendra Sai Institute of Medical Science & Research (VIMSAR)SambalpurIndia
  3. 3.Department of Bioscience and BiotechnologyFakir Mohan UniversityBalasoreIndia
  4. 4.School of Life SciencesSambalpur UniversitySambalpurIndia
  5. 5.Department of CardiologyGovt. Medical College and Super Specialty HospitalNagpurIndia
  6. 6.School of Life SciencesAIPH UniversityBhubaneswarIndia
  7. 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)SambalpurIndia

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