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

Heme toxicity plays a central role in the pathophysiology of Sickle Cell
Disease (SCD), contributing to severe complications such as vaso-occlusion
and acute chest syndrome. 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. Hemopexin-accessible heme (HAH) emerged as a refined
indicator of heme burden linked to pathways driving severe SCD
complications. A strong inverse correlation was observed between HAH and
hemopexin (R = –0.73, p < 0.001), suggesting that hemopexin
deficiency contributes to elevated HAH levels. Accurate characterization
of clinically relevant plasma heme species and understanding their effects
on SCD pathophysiology is essential for the development of new targeted
therapies. The data set contains individual measurement of total plamsa
heme, the heme species and the 85 biomarkers investigated in this study
(see description below). Full analyte names, the matrix, and units for all
analytes are shown in the corresponding "Variables" table.