Conjugated bilirubin triggers anemia by inducing erythrocyte death.

Abstract

UNLABELLED:

Hepatic failure is commonly associated with anemia, which may result from gastrointestinal bleeding, vitamin deficiency, or liver-damaging diseases, such as infection and alcohol intoxication. At least in theory, anemia during hepatic failure may result from accelerated clearance of circulating erythrocytes. Here we show that bile duct ligation (BDL) in mice leads to severe anemia despite increased reticulocyte numbers. Bilirubin stimulated suicidal death of human erythrocytes. Mechanistically, bilirubin triggered rapid Ca(2+) influx, sphingomyelinase activation, formation of ceramide, and subsequent translocation of phosphatidylserine to the erythrocyte surface. Consistent with our in vitro and in vivo findings, incubation of erythrocytes in serum from patients with liver disease induced suicidal death of erythrocytes in relation to their plasma bilirubin concentration. Consistently, patients with hyperbilirubinemia had significantly lower erythrocyte and significantly higher reticulocyte counts compared to patients with low bilirubin levels.

CONCLUSION:

Bilirubin triggers suicidal erythrocyte death, thus contributing to anemia during liver disease.

• Authors: Elisabeth Lang, Sergios Gatidis, Noemi F Freise, Hans Bock, Ralf Kubitz, Christian Lauermann, Hans Martin Orth, Caroline Klindt, Maximilian Schuier, Verena Keitel, Maria Reich, Guilai Liu, Sebastian Schmidt, Haifeng C Xu, Syed M Qadri, Diran Herebian, Aleksandra A Pandyra, Ertan Mayatepek, Erich Gulbins, Florian Lang, Dieter Häussinger, Karl S Lang, Michael Föller, Philipp A Lang
• Journal: Hepatology (Baltimore, Md.) (Hepatology) Vol. 61 Issue 1 Pg. 275-84 (Jan 2015) ISSN: 1527-3350 [Electronic] United States
• PMID: 25065608 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 The Authors. Hepatology published by Wiley Periodicals, Inc., on behalf of the American Association for the Study of Liver Diseases.

Chemical References

• Sphingomyelin Phosphodiesterase
• Bilirubin
• Calcium

Topics

• Aged
• Anemia (etiology)
• Animals
• Bilirubin (blood)
• Calcium (metabolism)
• Case-Control Studies
• Cell Death
• Erythrocytes (physiology)
• Female
• Healthy Volunteers
• Humans
• Liver Failure (blood, complications)
• Male
• Mice
• Middle Aged
• Sphingomyelin Phosphodiesterase (metabolism)