The Human Endogenous Protection System against Cell-Free Hemoglobin and Heme Is Overwhelmed in Preeclampsia and Provides Potential Biomarkers and Clinical Indicators.

Abstract

Preeclampsia (PE) complicates 3-8% of all pregnancies and manifests clinically as hypertension and proteinuria in the second half of gestation. The pathogenesis of PE is not fully understood but recent studies have described the involvement of cell-free fetal hemoglobin (HbF). Hypothesizing that PE is associated with prolonged hemolysis we have studied the response of the cell-free Hb- and heme defense network. Thus, we have investigated the levels of cell-free HbF (both free, denoted HbF, and in complex with Hp, denoted Hp-HbF) as well as the major human endogenous Hb- and heme-scavenging systems: haptoglobin (Hp), hemopexin (Hpx), α1-microglobulin (A1M) and CD163 in plasma of PE women (n = 98) and women with normal pregnancies (n = 47) at term. A significant increase of the mean plasma HbF concentration was observed in women with PE. Plasma levels of Hp and Hpx were statistically significantly reduced, whereas the level of the extravascular heme- and radical scavenger A1M was significantly increased in plasma of women with PE. The Hpx levels significantly correlated with maternal blood pressure. Furthermore, HbF and the related scavenger proteins displayed a potential to be used as clinical biomarkers for more precise diagnosis of PE and are candidates as predictors of identifying pregnancies with increased risk of obstetrical complications. The results support that PE pathophysiology is associated with increased HbF-concentrations and an activation of the physiological Hb-heme defense systems.