Heme Concentration As a Biomarker of Sickle Cell Disease Severity: Its Role in Steady-State and in Crisis Patients

Background : Sickle cell disease (SCD) is a heredity group of anemia characterized by hemolysis, chronic inflammation, and vaso-occlusive/painful crisis. The heme is a product of erythrocytes9 lyses and is increased in hemolytic diseases. Objectives : To investigate associations between hematological/biochemistry biomarkers and total plasma heme levels between SCD patients groups (in crisis and in steady-state) and healthy controls. To identify molecules related to hemolysis, inflammation, hepatic dysfunction, renal and lipid metabolism. Methods : We evaluated a total of 125 SCD steady-state patients, 22 SCD in crisis patients, and 32 healthy individuals age- and sex-matched with patients groups. Hematological analyses were performed by automatic cell counter, and hemoglobin profile by HPLC. Biochemistry analyses of inflammatory and infection markers, as well as lipid, hepatic, and kidney metabolism markers were investigated by immunochemistry assays. Plasma concentration of total free heme was measured by QuantiChrom Heme Assay Kit. Results : SCD patients groups (steady state and crisis) had higher heme concentration when compared to healthy individuals ( p r = -0.36, p .0001); hematocrit ( r = -0.38, p r = -0.34, p r = -0.42, p r = 0.35, p r = 0.40, p r = 0.19, p =0.04); monocytes count ( r = 0.36, p r = 0.54, p r = 0.22, p =0.01); AST ( r = 0.41, p r = 0.18, p= 0.04); serum iron ( r =0.21, p =0.03); total cholesterol ( r = 0.23, p =0.01); LDL-C ( r = 0.22, p= 0.02); VLDL-C ( r = 0.65, p r = 0.63, p Conclusions : The finding of similar heme concentration between steady state and crisis SCD patients may be explained by the hyperhemolysis phenomenon, showing that even in steady-state, these patients continue to have hemolysis and generate heme and reactive oxygen species. It was also shown that high concentration of free heme increases hemolytic and inflammatory biomarkers, such as LDH, bilirubin9s, reticulocytes count, and lipids, contributing to a severe clinical modulation of SCD. Disclosures No relevant conflicts of interest to declare.