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

Ann Hematol. 2019 Oct;98(10):2257-2265. doi: 10.1007/s00277-019-03776-x. Epub 2019 Aug 22.


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.

Keywords: Folic acid; Hemolysis; Homocysteine; Methyltetrahydrofolate reductase; Sickle cell anemia; Vaso-occlusive crisis.

Publication types

  • Clinical Trial
  • Multicenter Study

MeSH terms

  • Adolescent
  • Adult
  • Anemia, Sickle Cell* / blood
  • Anemia, Sickle Cell* / complications
  • Anemia, Sickle Cell* / genetics
  • Anemia, Sickle Cell* / physiopathology
  • Aspartate Aminotransferases / blood
  • Bilirubin / blood
  • Blood Platelets / metabolism
  • Female
  • Fetal Hemoglobin / genetics
  • Fetal Hemoglobin / metabolism
  • Hemolysis
  • Homocysteine / blood*
  • Homocysteine / genetics
  • Humans
  • L-Lactate Dehydrogenase / blood
  • Male
  • Methylenetetrahydrofolate Reductase (NADPH2) / blood
  • Methylenetetrahydrofolate Reductase (NADPH2) / genetics*
  • Middle Aged
  • Platelet Activation
  • Platelet Count
  • Polymorphism, Genetic*
  • Vascular Diseases* / blood
  • Vascular Diseases* / etiology
  • Vascular Diseases* / genetics
  • Vascular Diseases* / physiopathology


  • Homocysteine
  • Fetal Hemoglobin
  • L-Lactate Dehydrogenase
  • MTHFR protein, human
  • Methylenetetrahydrofolate Reductase (NADPH2)
  • Aspartate Aminotransferases
  • Bilirubin