Vitamin D Level and Its Correlation With Hemoglobin In Pediatric Sickle Cell Disease Patients

It has been well characterized that people living with sickle cell disease are more likely than the general population to be vitamin D deficient. New literature suggests there is an association between vitamin D deficiency and increased anemia in patients with chronic anemia. To date, this has been examined only in patients with end stage renal disease, heart failure, and anemia of other chronic diseases, but not in sickle cell disease, a chronic inflammatory disease with an elevation in inflammatory markers. Vitamin D has been shown to increase erythroid precursor proliferation by increasing erythropoietin sensitivity. It is also thought that vitamin D has pleiotropic effects, which may have influence on the bone marrow. Additionally, vitamin D has been shown to suppress pro-inflammatory cytokines, which causes a decrease in the anemia of chronic inflammation. Severe vitamin D deficiency also causes hyperparathyroidism, which leads to an inhibition of endogenous production of erythropoietin. Our hypothesis implies supplementation of vitamin D will improve anemia of vitamin D deficient sickle cell patients.

We utilized laboratory and demographic data from the Bronx Lebanon Hospital Center's patient electronic medical record between November 2009 and July 2013. Our sample included a population of 50 sickle cell disease patients aged 0 to 21 who were vitamin D deficient (serum 25-hydroxyvitamin D (25-OHD) <30ng/ml). Sickle cell disease types included SS (64%), SC (32%), Sβ⁺ thalassemia and Sβ⁰ thalassemia (4%). Using a linear mixed model with an autoregressive correlation structure to account for variance within the subject, we examined the association between time dependent 25-OHD level (ng/ml) and hemoglobin in (g/dl), as well as between 25-OHD and reticulocyte percentage over time in days. We began at the time of first supplementation of 25-OHD to the most recent blood levels in each patient.

After adjusting for mean corpuscular volume (MCV), hemoglobin, sickle cell type and hydroxyurea (Table 1), there was a linear increase in reticulocyte percentage over time associated with increasing 25-OHD levels (β = 0.000060, SE = 0.000030, p =0.050). However, after controlling for MCV, gender, race, sickle cell type, and hydroxyurea (Table 2), we found trend of a negative association between 25-OHD and hemoglobin levels, which was statistically significant (β = -0.000017, SE = 0.000007, p =0.017).

Our results did not support our original hypothesis, which stated that supplementation of vitamin D in vitamin D deficient sickle cell patients would lead to an improvement in anemia. However, a trend was noted of a decrease in hemoglobin with increasing 25-OHD. In turn, there was a statistically significant increase in reticulocyte percentage with increasing 25-OHD. This is suggestive that there is increased hemolysis with increased erythropoiesis caused by increasing 25-OHD. This is seen even when controlling for patients taking hydroxyurea. Further study is required to elucidate this possible correlation. It is important to examine this relationship further, as supplementing vitamin D in vitamin D deficient sickle cell disease patients is becoming standard of care for improvement in bone density. It is unclear what potential implications this may have on increased production of sickle cells from the bone marrow, including a possible increase in hemolysis and a worsened anemia.

Seelaboyina:Bronx Lebanon Hospital: Employment.