Hemoglobin-driven pathophysiology is an in vivo consequence of the red blood cell storage lesion that can be attenuated in guinea pigs by haptoglobin therapy

Baek, Jin Hyen; D’Agnillo, Felice; Vallelian, Florence; Pereira, Cláudia; Williams, M.; Jia, Yiping; Schaer, Dominik J.; Buehler, Paul W.

doi:10.1172/jci59770

Cited by 243 publications

(254 citation statements)

References 38 publications

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“…These studies suggest that high-volume transfusions of older blood, but not fresh blood, result in posttransfusion intravascular and extravascular hemolysis that approaches a 15% -20% loss of transfused RBCs within 24 h. Transfusion of older, rather than fresh, blood caused an acute hypertensive response, hemoglobinuria, acute renal failure, and vascular injury ( Fig. 1) (Baek et al 2012). Infusion of transfused old blood with the specific Hb scavenger haptoglobin (Hp) attenuated several of the transfusion-related adverse effects.…”

Section: Transfusion Of Stored Bloodmentioning

confidence: 91%

“…Animal models of RBC transfusion have been designed to explore the possible roles of intravascular hemolysis and cell-free Hb in the pathophysiologic consequences of the massive transfusion of older stored blood in guinea pigs (Baek et al 2012). These studies suggest that high-volume transfusions of older blood, but not fresh blood, result in posttransfusion intravascular and extravascular hemolysis that approaches a 15% -20% loss of transfused RBCs within 24 h. Transfusion of older, rather than fresh, blood caused an acute hypertensive response, hemoglobinuria, acute renal failure, and vascular injury ( Fig.…”

Section: Transfusion Of Stored Bloodmentioning

confidence: 99%

“…The primary acute pathophysiologic responses to extracellular Hb in plasma are blood pressure elevation (Rother et al 2005) and pro-oxidative toxicity occurring in vascular and renal tissues Baek et al 2012). The processes driving Hb-induced toxicity are depicted in Figure 2 and likely involve a complex interaction between NO balance, oxidation, and inflammation.…”

Section: Mechanisms Of Hemoglobin-mediated Adverse Effectsmentioning

confidence: 99%

“…This suggests that some degree of tolerance to extracellular Hb in circulation occurs with longer-term exposures. If analyses of Hb-mediated vascular wall injury are considered, however, the duration of sustained intravascular Hb exposure appears to be a critical determinant of the cumulative toxicity (Baek et al 2012).…”

Section: Nitric Oxide Consumption-systemic and Phmentioning

confidence: 99%

“…The biochemistry of these reactions has been the focus of Hb research for decades. More recently, however, these Hb reactions were examined as a potential cause of adverse pathophysiologic processes that accompany red blood cell (RBC) destruction (i.e., hemolysis) and the accumulation of extracellular free Hb (Baek et al 2012;Gladwin et al 2012). Other biologic activities of extracellular free Hb can be traced back either to direct interactions of its globin or heme components with specific cellular receptors and signaling pathways, or to the secondary effects of heme breakdown by the heme oxygenases.…”

mentioning

confidence: 99%

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Cell-Free Hemoglobin and Its Scavenger Proteins: New Disease Models Leading the Way to Targeted Therapies

Schaer

Buehler

2013

Cold Spring Harbor Perspectives in Medicine

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Section: Transfusion Of Stored Bloodmentioning

confidence: 91%

Section: Transfusion Of Stored Bloodmentioning

confidence: 99%

Section: Mechanisms Of Hemoglobin-mediated Adverse Effectsmentioning

confidence: 99%

Section: Nitric Oxide Consumption-systemic and Phmentioning

confidence: 99%

mentioning

confidence: 99%

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Cell-Free Hemoglobin and Its Scavenger Proteins: New Disease Models Leading the Way to Targeted Therapies

Schaer

Buehler

2013

Cold Spring Harbor Perspectives in Medicine

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Tangential flow filtration of haptoglobin

Pires

Palmer

2020

Biotechnology Progress

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Haptoglobin (Hp) is a plasma glycoprotein that scavenges cell-free hemoglobin (Hb). Hp has various potential therapeutic applications, but it has been mainly studied for treatment of acute hemolytic conditions that can arise from situations such as massive blood transfusion, infusion of stored red blood cells, severe burns, trauma, sepsis, radiation injury, and others. Therefore, Hp may also be beneficial during chronic hemolytic disease states such as hereditary spherocytosis, nocturnal hemoglobinuria, sickle-cell anemia, and malaria. Various methods have been developed to purify Hp from plasma or plasma fractions. However, none of these methods have exploited the large molecular weight (MW) range distribution of Hp polymers to easily isolate Hp from other plasma proteins. The present study used tangential flow filtration (TFF) to isolate polymeric Hp from plasma proteins using human Fraction IV (FIV) as the starting material. After removal of insoluble material from a suspension of FIV paste, the protein mixture was clarified on a 0.2 μm hollow fiber (HF) TFF filter. The clarified protein solution was then bracketed based on protein MW using HF filters with MW cutoffs (MWCOs) of 750, 500, and 100 kDa. Using untreated FIV, the Hp purity of the main bracket was~75% with a total Hb binding capacity (HbBC) yield of 1.2 g starting from 500 g of FIV paste. However, pretreatment of FIV with fumed silica to remove lipoproteins increased Hp purity to >95% with a HbBC yield of 1.7 g per 500 g of FIV. Taken together this study provides a novel and scalable method to purify Hp from plasma or plasma fractions.

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Red blood cell exchange: 2015 American Society for Apheresis consensus conference on the management of patients with sickle cell disease

Sarode

Ballas

García³

et al. 2016

J of Clinical Apheresis

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The American Society for Apheresis (ASFA) conducted a one-day consensus conference on red blood cell exchange (RBCx) in sickle cell disease (SCD) during its annual meeting in San Antonio, TX, on May 5, 2015. The authors of this article, a subcommittee of ASFA's Clinical Applications Committee, developed several questions with regard to pathophysiology of SCD and use of RBCx in the management of various complications. These questions were provided to the seven invited speakers who are the experts in the field of SCD. Two experts in the field moderated the proceedings of the conference, which was attended by more than 150 participants. After each presentation, there was a summary of the main points by the moderators and an open discussion with questions from the audience. A video recording of the proceedings, as well as each presentation, was made available to the authors. Each author's summary was reviewed and approved by the respective speaker before submission of this manuscript. The subcommittee also developed several key questions to generate a consensus amongst the speakers on key issues for using RBCx for patients with SCD.

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Hemoglobin-driven pathophysiology is an in vivo consequence of the red blood cell storage lesion that can be attenuated in guinea pigs by haptoglobin therapy

Cited by 243 publications

References 38 publications

Cell-Free Hemoglobin and Its Scavenger Proteins: New Disease Models Leading the Way to Targeted Therapies

Cell-Free Hemoglobin and Its Scavenger Proteins: New Disease Models Leading the Way to Targeted Therapies

Tangential flow filtration of haptoglobin

Red blood cell exchange: 2015 American Society for Apheresis consensus conference on the management of patients with sickle cell disease

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