Plasma heme pool compartmentalization is linked to pathophysiology in sickle cell disease

The continuous release of hemoglobin and heme from increased intravascular hemolysis can exceed the capacity of protective scavenger proteins, leading to heme accumulation in plasma. Interactions with various binding partners result in the formation of different plasma heme species and the compartmentalization of the plasma heme pool.

In an observational biomarker study, we used novel bioanalytical assays to quantify plasma heme species in 36 stable-state SCD patients and 36 age, sex, and ethnicity-matched controls. Our results revealed substantially different compartmentalization of plasma heme, despite similar levels of total plasma heme in SCD patients (50 µmol/L) and controls (43 µmol/L). Using a correlation analysis across 85 biomarkers, we examined the association of specific heme species with SCD pathophysiology.