A common complication of acute cardiac failure (AHF) is anaemia, which negatively influences the clinical outcome. Causes of anaemia include enhanced eryptosis, a suicidal erythrocyte death characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation. Signalling triggering eryptosis include oxidative stress, increase of cytosolic Ca2+-activity ([Ca2+]i) and ceramide. The present study explored whether AHF is associated with accelerated eryptosis.Materials and Methods
Erythrocytes were drawn from healthy volunteers (n = 10) and patients hospitalized for AHF (n = 22). Phosphatidylserine exposure was estimated from annexin-V-binding, cell volume from forward scatter, [Ca2+]i from Fluo3-fluorescence, ceramide abundance utilizing specific antibodies and reactive oxygen species (ROS) abundance from 2′,7′-dichlorodihydrofluorescein diacetate (DCFDA) fluorescence, as determined by flow cytometry.Results
In AHF-patients, haemoglobin concentration (11·5 ± 0·5 g/dL), and haematocrit (35·6 ± 1·2%) were significantly lower than haemoglobin concentration (14·1 ± 0·4 g/dL), and haematocrit (40·1 ± 1·0%) in healthy volunteers, even though reticulocyte number was significantly higher in AHF patients (2·3 ± 0·3%) than in healthy volunteers (1·1 ± 0·2%). The percentage of erythrocytes exposing phosphatidylserine was significantly higher in AHF patients (1·8 ± 0·1%) than in healthy volunteers (1·2 ± 0·2%). The forward scatter was significantly lower and the ROS abundance significantly larger in AHF patients than in healthy volunteers. In erythrocytes drawn from healthy volunteers, phosphatidylserine and ROS abundance was increased to significantly higher values following a 24 h treatment with plasma from AHF patients than with plasma from healthy volunteers.Conclusion
AHF leads to anaemia despite increased reticulocyte number and at least partially due to enhanced eryptosis. Underlying mechanisms include oxidative stress imposed by a plasma borne component.