Preservation of Recipient Plasma Sphingosine-1-Phosphate Levels Reduces Transfusion-related Acute Lung Injury.

Cold stored platelets (CS) are once again being reintroduced for clinical use. Transfused CS offer benefits over room temperature stored platelets (RTS) such as increased hemostatic effects and prolongation of shelf-life. Despite these advantages little is known about their association with transfusion-related acute lung injury (TRALI). TRALI is associated with prolonged storage RTS and has a mortality of > 15%. Determining the safety of CS is important considering their proposed use in TRALI-vulnerable populations with systemic inflammation such as surgical or trauma patients. Donor platelet-derived ceramide causes TRALI whereas donor platelet sphingosine-1-phosphate (S1P) is barrier protective. Females have higher plasma levels of S1P than males. Cold temperatures increase S1P levels in cells. Therefore, we hypothesized that female (donors or recipients) and/or CS would decrease TRALI. To test this, we compared how male and female donor and recipient allogeneic platelet transfusions of CS (40 C) versus RTS (230 C) stored for five days influence murine TRALI. Transfusion of CS significantly reduced recipient lung tissue wet-to-dry ratios, bronchoalveolar lavage total protein, lung tissue myeloperoxidase enzyme activity, histological lung injury scores and increased plasma sphingosine-1-phosphate (S1P) levels compared with RTS transfusions. Female as opposed to male recipients had less TRALI and higher plasma S1P levels. Female donor mouse platelets had higher S1P levels compared to males. Mouse and human CS platelets had increased S1P levels compared with RTS platelets. Higher recipient plasma S1P levels appears protective considering females, and males receiving platelets from females or male CS platelets had less TRALI.