Haptoglobin Genotypes Associated with Vaso-Occlusive Crisis in Sickle Cell Anemia Patients of Eastern India

Abstract

Sickle cell anemia is hallmarked by hemolysis, which releases hemoglobin (Hb) into the plasma promoting vaso-occlusive crisis (VOC). Haptoglobin (Hp) clears free Hb and decreases Hb-related pathophysiology in sickle cell anemia. There are two alleles (HP1 and HP2) and three genotypes (HP1-1, HP1-2 and HP2-2) of Hp with different frequencies in different populations. This study involved Hp level and genotype among normal and sickle cell anemia patients with varying severity of VOC. A total of 297 sickle cell anemia patients and 98 healthy controls were selected for the study. The sickle cell anemia patients were categorized as ‘mild-phenotype’ with no pain episodes and ‘severe-phenotype’ as having three or more acute pain episodes in the preceding 12 months. The Hp level was significantly lower (p < 0.001) in sickle cell patients anemia than controls; HP1-1 genotype had a higher Hp level compared to HP1-2 and HP2-2 (p < 0.05). Turkey-Kramer multiple comparison tests showed that mild and severe phenotypes have significant differences (p < 0.05) in Hb F%, Hb, platelet count, aspartate aminotransferase (AST), alanine aminotransferase (ALT), direct-bilirubin (Bil-D), total-bilirubin (Bil-T), lactate dehydrogenase (LDH) and Hp level. Pearson correlation revealed that Hp level has a positive (p < 0.05) correlation with Hb F%, Hb, packed cell volume (PCV) and serum urea; in contrast its level is negatively correlated with AST, ALT, Bil-T and LDH. A significantly higher frequency of HP2 allele and HP2-2 genotypes was found in severe phenotypes. In the studied population, it was found that higher HP2 frequency, low Hp level and more hemolysis favors the onset of VOC in sickle cell anemia.

Keywords:

• Haptoglobin (Hp)
• sickle cell anemia
• vaso-occlusive crisis (VOC)

Acknowledgments

We extend our thanks to the Director as well as Dean and Principal of VIMSAR, Burla, Sambalpur, Odisha State, India for permitting us to carry out this study. Authors’ contributions: S. Meher, P.K. Mohanty and B.P. Dash conceptualized and designed this study. The data was collected by S. Meher, S. Sahoo, S. Dehury and B.P. Jit. The laboratory work was done by S. Meher. The data was analyzed and interpretated by S. Meher, P.K. Mohanty, S. Patel, M.K. Mohapatra, K. Das, P. Das, and B.P. Dash. All the authors wrote and approved the final manuscript.

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

Additional information

Funding

The authors thank National Health Mission, Odisha State, India for fund support of our study.