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Synapse
June 3, 2022Blood167 citationsOpen Access

Hemolysis, free hemoglobin toxicity, and scavenger protein therapeutics

FVFlorence VallelianPBPaul W. BuehlerDSDominik J. Schaer

Key Points

  • To review the physiological pathways of red blood cell and hemoglobin clearance and outline the therapeutic potential of scavenger proteins in pathological hemolysis.
  • Reviewed cellular and metabolic pathways of red blood cell clearance by erythrophagocytes.
  • Assessed biochemical scavenging mechanisms mediated by haptoglobin and hemopexin.
  • Evaluated the pathological impact of scavenger depletion and current clinical pipelines for scavenger protein therapeutics.
  • Erythrophagocytes, haptoglobin, and hemopexin normally neutralize extracellular hemoglobin and heme while recycling iron.
  • Pathological hemolysis overwhelms endogenous macrophage clearance and scavenger protein synthesis, driving disease progression.
  • Scavenger protein-based therapeutics are currently in clinical development to prevent cell-free hemoglobin toxicity across diverse hemolytic conditions.

Abstract

During hemolysis, erythrophagocytes dispose damaged red blood cells. This prevents the extracellular release of hemoglobin, detoxifies heme, and recycles iron in a linked metabolic pathway. Complementary to this process, haptoglobin and hemopexin scavenge and shuttle the red blood cell toxins hemoglobin and heme to cellular clearance. Pathological hemolysis outpaces macrophage capacity and scavenger synthesis across a diversity of diseases. This imbalance leads to hemoglobin-driven disease progression. To meet a void in treatment options, scavenger protein-based therapeutics are in clinical development.

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Cite This Study

Vallelian et al. (2022) studied this question.

synapsesocial.com/papers/69d967a91ad561c673684087https://doi.org/10.1182/blood.2022015596
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Exchange of Heme among Hemoglobins and between Hemoglobin and Albumin1968 · 416 citations
  2. 2The Globin-based Free Radical of Ferryl Hemoglobin Is Detected in Normal Human Blood1997 · 120 citations
  3. 3Action of haptoglobin on the peroxidase catalysis of hemoglobin; new theory on the constitution of enzymes.2010 · 4 citations
  4. 4Modular Platform for the Development of Recombinant Hemoglobin Scavenger Biotherapeutics2021 · 14 citations
  5. 5Cell-Free Hemoglobin and Its Scavenger Proteins: New Disease Models Leading the Way to Targeted Therapies2013 · 95 citations