The goal here is to describe our current understanding of
heme metabolism and the deleterious effects of "free"
heme on immunological processes, endothelial function, systemic
inflammation, and various end-organ tissues (e.g., kidney, lung, liver, etc.), with particular attention paid to the role of
hemopexin (HPX). Because
heme toxicity is the impetus for much of the pathology in
sepsis,
sickle cell disease (SCD), and other hemolytic conditions, the
biological importance and clinical relevance of HPX, the predominant
heme binding protein, is reinforced. A perspective on the function of HPX and
haptoglobin (Hp) is presented, updating how these two
proteins and their respective receptors act simultaneously to protect the body in clinical conditions that entail
hemolysis and/or systemic intravascular (IVH)
inflammation. Evidence from longitudinal studies in patients supports that HPX plays a Hp-independent role in genetic and non-genetic hemolytic diseases without the need for global Hp depletion. Evidence also supports that HPX has an important role in the prognosis of complex illnesses characterized predominantly by the presence of
hemolysis, such as SCD,
sepsis,
hemolytic-uremic syndrome, and conditions involving IVH and
extravascular hemolysis (EVH), such as that generated by
extracorporeal circulation during
cardiopulmonary bypass (CPB) and from
blood transfusions. We propose that quantitating the amounts of plasma
heme, HPX, Hb-Hp,
heme-HPX, and
heme-
albumin levels in various disease states may aid in the diagnosis and treatment of the above-mentioned conditions, which is crucial to developing targeted
plasma protein supplementation (i.e., "replenishment")
therapies for patients with
heme toxicity due to HPX depletion.