Plasma levels of sphingosine 1-phosphate are strongly correlated with haematocrit, but variably restored by red blood cell transfusions

Anaemia and RBC (red blood cell) transfusion may be associated with worse clinical outcomes, especially with longer blood storage duration prior to transfusion. The mechanisms underlying these harmful effects are unknown. RBCs have been proposed to buffer plasma SIP (sphingosine 1-phosphate), a lysophospholipid essential for the maintenance of endothelial integrity and important in the regulation of haematopoietic cell trafficking. The present study examined the effect of anaemia, RBC transfusion and RBC storage duration on plasma SIP levels. Plasma SIP from 30 individuals demonstrated a linear correlation with Hct (haematocrit; R-2 = 0.51, P < 0.001) with no evidence for a plateau at Hct values as low as 19%. RBC transfusion in 23 anaemic patients with baseline mean Hct of 22.2 +/- 0.34% (value is the mean +/- S.D.) increased Hct to 28.3 +/- 0.6% at 72 h. Despite an Hct increase, RBC transfusion failed to elevate plasma S I P consistently. A trend towards an inverse correlation was observed between RBC storage duration and the post-transfusion increase in plasma S I R After 30 days of storage, RBC S I P decreased to 19% of that observed in fresh (3-7-day-old) RBC segments. RBC membranes contain low levels of both S I P phosphatase and S I P lyase activities that may account for the decline in S I P levels with storage. Our results support a role for RBCs in buffering plasma SIP and identify a disturbance in the capacity after transfusion. Changes in S I P content may contribute to an RBC storage lesion. Further studies should investigate the clinical significance of alterations in circulating SIP levels and the potential value of enriching stored RBCs with SIR