Conjugated bilirubin triggers anemia by inducing erythrocyte death. Issue 1 (24th November 2014)

• Record Type: Journal Article
• Authors: Lang, Elisabeth; Gatidis, Sergios; Freise, Noemi F.; Bock, Hans; Kubitz, Ralf; Lauermann, Christian; Orth, Hans Martin; Klindt, Caroline; Schuier, Maximilian; Keitel, Verena; Reich, Maria; Liu, Guilai; Schmidt, Sebastian; Xu, Haifeng C.; Qadri, Syed M.; Herebian, Diran; Pandyra, Aleksandra A.; Mayatepek, Ertan; Gulbins, Erich; Lang, Florian; Häussinger, Dieter; Lang, Karl S.; Föller, Michael; Lang, Philipp A.
• Is Part Of: Hepatology. Volume 61:Issue 1(2015:Jan.)
• Page Start: 275
• Page End: 284
• Publication Date: 2014-11-24
• Subjects: Heart -- Diseases -- Nursing -- Periodicals; Lungs -- Diseases -- Nursing -- Periodicals; Intensive care nursing -- Periodicals; Foie -- Maladies -- Périodiques; 616.362
• DOI: 10.1002/hep.27338
• Languages: English
• ISSNs: 0270-9139

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>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 Ca²⁺ influx, sphingomyelinase activation, formation of ceramide, and subsequent translocation of phosphatidylserine to the erythrocyte surface. Consistent with our <italic>in vitro</italic> and <italic>in vivo</italic> 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. <italic>Conclusion</italic>: Bilirubin triggers suicidal erythrocyte death, thus contributing to anemia during liver disease. (H<sc>epatology</sc> 2015;61:275–284)</p> </abstract>