Microparticles in stored red blood cells as potential mediators of transfusion complications

Abstract

This article reviews evidence for the involvement of cell-derived microparticles (MP) in transfusion-related adverse events. The controversy concerning possible added risk of older vs. fresher stored blood is also reviewed, and is consistent with the hypothesis that MP are involved with adverse events. Although all types of circulating MP are discussed, the emphasis is on red cell-derived MP (RMP). The evidence is particularly strong for involvement of RMP in transfusion-related acute lung injury (TRALI), but also for post-operative thrombosis. However, this evidence is largely circumstantial. Work in progress to directly test the hypothesis is also briefly reviewed.

Immunoregulatory Effects of Stored Red Blood Cells

“…36 Many complement system components and immunoglobulins are enriched in RBC microparticles, which is consistent with a proinflammatory potential. 37 In addition, microparticles express the procoagulant phosphatidylserine and the number of phosphatidylserine-enriched RBC microparticles increases with storage time.…”

Microparticles and acute lung injury

“…20,120). MPs have also been directly associated with immunomodulatory effector molecules such as RMP-and PMP-derived CD40L, IgG, and complement found in stored blood products (80). Immunomodulatory and proinflammatory effects of MPs may be particularly relevant in the context of transfusion-related ALI (TRALI), because storage of blood products will propel for- mation of MPs (25,33,144) that will subsequently activate PMNs (80).…”

“…Beyond TF expression, MPs expose large amounts of PS on their outer membranes, thus creating an ideal surface for activation of the coagulation pathway (148). In addition, MPs generate and release other prothrombotic factors including thrombin (80) or vWF multimers that can promote and stabilize platelet aggregation (20). In summary, there is ample evidence from in vitro animal and human studies demonstrating the formation of MPs with procoagulant activity under inflammatory conditions and in ALI in both the vascular and alveolar compartment, where they are likely to contribute pivotally to the hypercoagulable and hypofibrinolytic state characteristic for ALI/ARDS.…”

“…RMPs typically form after 10 days of storage, whereas PMPs accumulate earlier within days, and levels of both can be significantly reduced if packed cells are leukoreduced or in the presence of storage additives such as glucose, pyruvate, inosine, adenine, and phosphate (80). Storage of platelets with PGE 1 , theophylline, or aprotinin as well as pharmacological inhibition of ␣ IIb ␤ 3 -integrin signaling have been proposed to reduce ex vivo PMP production (25,33) and may thus help to reduce PMN activation and sequestration in the lungs subsequent to transfusion of stored blood products.…”

“…MPs have also been directly associated with immunomodulatory effector molecules such as RMP-and PMP-derived CD40L, IgG, and complement found in stored blood products (80). Immunomodulatory and proinflammatory effects of MPs may be particularly relevant in the context of transfusion-related ALI (TRALI), because storage of blood products will propel for- mation of MPs (25,33,144) that will subsequently activate PMNs (80). Taken together, MPs of diverse cellular origins including LMPs, PMPs, RMPs, NMPs, and EMPs directly or indirectly promote inflammatory responses and may thus propel ALI, in that they stimulate cytokine release and promote PMN activation, migration, and PMN-platelet interaction.…”