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Hemolysis and free hemoglobin revisited: exploring hemoglobin and hemin scavengers as a novel class of therapeutic proteins


Schaer, D J; Buehler, P W; Alayash, A I; Belcher, J D; Vercellotti, G M (2013). Hemolysis and free hemoglobin revisited: exploring hemoglobin and hemin scavengers as a novel class of therapeutic proteins. Blood, 121(8):1276-1284.

Abstract

Hemolysis occurs in many hematologic and non-hematologic diseases. Extracellular hemoglobin (Hb) has been recognized to trigger specific pathophysiologies that are associated with adverse clinical outcomes in patients with hemolysis, such as acute and chronic vascular disease, inflammation, thrombosis and renal impairment. Among the molecular characteristics of extracellular Hb, translocation of the molecule into the extravascular space, oxidative and nitric oxide reactions, hemin release and molecular signaling effects of hemin appear to be the most critical. Limited clinical experience with a plasma-derived haptoglobin product in Japan and more recent preclinical animal studies suggest that the natural Hb and hemin scavenger proteins haptoglobin (Hp) and hemopexin (Hpx) have a strong potential to neutralize the adverse physiologic effects of Hb and hemin. This includes conditions that are as diverse as red blood cell transfusion, sickle cell disease, sepsis and extracorporeal circulation. This perspective reviews the principal mechanisms of Hb and hemin toxicity in different disease states, updates how the natural scavengers efficiently control these toxic moieties, and explores critical issues in the development of human plasma-derived Hp and Hpx as therapeutics for patients with excessive intravascular hemolysis.

Abstract

Hemolysis occurs in many hematologic and non-hematologic diseases. Extracellular hemoglobin (Hb) has been recognized to trigger specific pathophysiologies that are associated with adverse clinical outcomes in patients with hemolysis, such as acute and chronic vascular disease, inflammation, thrombosis and renal impairment. Among the molecular characteristics of extracellular Hb, translocation of the molecule into the extravascular space, oxidative and nitric oxide reactions, hemin release and molecular signaling effects of hemin appear to be the most critical. Limited clinical experience with a plasma-derived haptoglobin product in Japan and more recent preclinical animal studies suggest that the natural Hb and hemin scavenger proteins haptoglobin (Hp) and hemopexin (Hpx) have a strong potential to neutralize the adverse physiologic effects of Hb and hemin. This includes conditions that are as diverse as red blood cell transfusion, sickle cell disease, sepsis and extracorporeal circulation. This perspective reviews the principal mechanisms of Hb and hemin toxicity in different disease states, updates how the natural scavengers efficiently control these toxic moieties, and explores critical issues in the development of human plasma-derived Hp and Hpx as therapeutics for patients with excessive intravascular hemolysis.

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Contributors:Division of Hematology, Oncology, and Transplantation, University of Minnesota Medical School
Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic and Policlinic for Internal Medicine
04 Faculty of Medicine > Center for Integrative Human Physiology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:2013
Deposited On:07 Feb 2013 11:40
Last Modified:06 Aug 2017 04:56
Publisher:American Society of Hematology
ISSN:0006-4971
Additional Information:This research was originally published in Blood. Schaer, D J; Buehler, P W; Alayash, A I; Belcher, J D; Vercellotti, G M (2012). Hemolysis and free hemoglobin revisited: exploring hemoglobin and hemin scavengers as a novel class of therapeutic proteins. Blood:Epub ahead of print. Copyright by the American Society of Hematology.
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1182/blood-2012-11-451229
PubMed ID:23264591

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