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When might transferrin, hemopexin or haptoglobin administration be of benefit following the transfusion of red blood cells?

Buehler, Paul W.*; Karnaukhova, Elena*

doi: 10.1097/MOH.0000000000000458
TRANSFUSION MEDICINE AND IMMUNOHEMATOLOGY: Edited by Steven L. Spitalnik

Purpose of review After transfusion, a percentage of red blood cells undergo hemolysis within macrophages. Intravascular exposures to hemin and hemoglobin (Hb) can occur after storage bag hemolysis, some transfusion reactions, during use of medical assist devices and in response to bacterial hemolysins. Proteins that regulate iron, hemin and Hb either become saturated after iron excess (transferrin, Tf) or depleted after hemin (hemopexin, Hpx) and Hb (haptoglobin, Hp) excess. Protein saturation or stoichiometric imbalance created by transfusion increases exposure to non-Tf bound iron, hemin and Hb. Tf, Hpx and Hp are being developed for hematological disorders where iron, hemin and Hb contribute to pathophysiology. However, complexed to their ligands, each represents a potential iron source for pathogens, which may complicate the use of these proteins.

Recent findings Erythrophagocytosis by macrophages and processes of cell death that lead to reactive iron exposure are increasingly described. In addition, the effects of transfusion introduced circulatory hemin and Hb are described in the literature, particularly following large volume transfusion, infection and during concomitant medical device use.

Summary Supplementation with Tf, Hpx and Hp suggests therapeutic potential in conditions of extravascular/intravascular hemolysis. However, their administration following transfusion may require careful assessment of concomitant disease.

Laboratory of Biochemistry and Vascular Biology, Division of Blood Components and Devices, Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, USA

Correspondence to Paul W. Buehler, PharmD, PhD, Laboratory of Biochemistry and Vascular Biology, Division of Blood Components and Devices, Center for Biologics Evaluation and Research, US Food and Drug Administration, 10903 New Hampshire Ave, Silver Spring, MD 20993, USA. Tel: +1 240 402 9411; e-mail: paul.buehler@fda.hhs.gov

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