Biological response modifiers in photochemically pathogen-reduced versus untreated apheresis platelet concentrates.

The platelet storage lesion (PSL) is a term often used for the sum of the deleterious changes in structure and function that occur to platelets (PLTs) in platelet concentrates (PCs) during storage under blood bank conditions. One of the features of the PSL is gradual accumulation in the PCs of various biological response modifiers.1–3 It has been suggested that some of these may induce immunosuppression in the recipients, a condition often referred to as transfusion-related immunomodulation (TRIM).4 Both lysophosphatidylcholines5 and soluble CD154 (sCD40 ligand) accumulate during storage of PCs and have been shown to be involved in transfusion-related acute lung injury (TRALI)6,7 and other adverse transfusion reactions.8,9 TRALI is a rare but potentially fatal complication of transfusion and has for years been the most common cause of transfusion-related fatalities in the United States.10 Most frequently implicated in TRALI are products with high plasma content, such as fresh-frozen plasma (FFP) or PCs. In addition to substances implicated in TRALI other important biological response modifiers may accumulate in PCs during storage. One of these substances is vascular endothelial growth factor (VEGF), which has numerous biological effects:11 VEGF has been suggested to be implicated in atherosclerosis,12 acts as an angiogenic factor upon vascular injury,12 stimulates angiogenesis associated with tumor growth, and may be assumed to decrease effectiveness of cancer therapy by binding monoclonal antibodies directed against growth factors of tumor origin.11 Despite numerous studies on the immunomodulative effects of transfusion the total impact of TRIM is not fully elucidated.13 Some early studies report positive effects, where transfusion has been linked to improved clinical outcome in renal transplantation,14,15 while others suggest significant immunosuppression in recipients, possibly leading to increased rate of recurrence of cancer16 and postoperative bacterial infections.17,18 Storage of PCs at 22 ± 2°C with constant agitation is associated with a significant risk for transfusion-associated septicemia. A strategy to decrease this risk is to implement one of two pathogen reduction (PR) systems approved for PCs. Both the INTERCEPT Blood System (Cerus Corp., Concord, CA) and the Mirasol Pathogen Reduction Technology (Mirasol PRT, TerumoBCT, Lake-wood, CO) target DNA and RNA in pathogens and white blood cells (WBCs), thereby inhibiting transcription and translation. A large number of reports and clinical studies conclude that PR treatment of PCs is well suited for use. However, there are clear indications of enhanced storage lesion in the PR-treated PCs19,20 although these changes are considered to be of minor clinical importance.21 The aim of this work was to investigate whether the INTERCEPT PR process has an impact on the amount of accumulated lysophosphatidylcholines, sCD154, VEGF, or other immunomodulative substances in apheresis PCs, compared to untreated PCs. Furthermore, we have examined to what extent accumulated biological response modifiers in PCs affect the cytokine release of heparinized whole blood after addition of LPS. Finally, we assessed the capacity of the PC supernatants to prime neutrophils (PMNs), which is the most important cell type in the development of TRALI.