Hemolysis and accumulation of cell-free hemoglobin (Hb) in the circulation or in confined tissue compartments such as the subarachnoid space is an important driver of disease. Haptoglobin is the Hb binding and clearance protein in human plasma and an efficient antagonist of Hb toxicity resulting from physiological red blood cell turnover. However, endogenous concentrations of haptoglobin are insufficient to provide protection against Hb-driven disease processes in conditions such as sickle cell anemia, sepsis, transfusion reactions, medical-device associated hemolysis, or after a subarachnoid hemorrhage. As a result, there is increasing interest in developing haptoglobin therapeutics to target ‘toxic’ cell-free Hb exposures. Here, we discuss key concepts of Hb toxicity and provide a perspective on the use of haptoglobin as a therapeutic protein.

血液中或循环中或蛛网膜下腔等狭窄组织隔室中无细胞血红蛋白（Hb）的溶血和积聚是疾病的重要驱动因素。结合珠蛋白是人血浆中的Hb结合和清除蛋白，是生理性红细胞更新产生的Hb毒性的有效拮抗剂。但是，内源性触珠蛋白的浓度不足以在镰状细胞性贫血，败血症，输血反应，医疗器械相关溶血或蛛网膜下腔出血等情况下提供抗Hb驱动疾病的保护作用。结果，人们越来越感兴趣的是开发针对“无毒”无细胞血红蛋白接触的触珠蛋白疗法。在这里，我们讨论了Hb毒性的关键概念，并提供了将触珠蛋白用作治疗性蛋白质的观点。