BACKGROUND:The pathomechanisms of morbidity due to blood transfusions are not yet entirely understood. Elevated levels of red blood cell-derived microparticles (RMPs) are found in coagulation-related pathologies and also in stored blood. Previous research has shown that RMPs mediate transfusion-related complications by the intrinsic pathway. We hypothesized that RMPs might play a role in post-transfusion thrombotic complications by enhancing procoagulant activity also through the extrinsic pathway of coagulation. STUDY DESIGN AND METHODS:In this laboratory study, blood from 18 healthy volunteers was stimulated with microparticles from expired stored red blood cells. Various clotting parameters were recorded. Flow cytometry, enzyme-linked immunosorbent assays, and real-time polymerase chain reaction were used to investigate possible mediating mechanisms. RESULTS:The addition of RMPs shortened the clotting time from 194 to 161 seconds (p < 0.001). After incubation with RMPs, there was increased expression of tissue factor (TF) on monocytes and in plasma. TF messenger RNA expression increased in a timedependent and concentration-dependent manner. There was a significant induction of interleukin-1b and interleukin-6. After stimulation with RMPs, there was a significant increase in the number of activated platelets, an increased percentage of PAC-1/CD62P (procaspase activating compound-1/platelet surface P-selectin) double-positive platelets, and an increased number of platelet-neutrophil duplets and platelet-monocyte duplets, indicating enhanced interaction of platelets with neutrophils and monocytes. Levels of CXCL-8 (C-X-C motif chemokine ligand 1) and interleukin-6 were significantly higher after treatment with RMPs. CONCLUSION:Our results suggest that RMPs trigger coagulation through TF signaling, induce the secretion of proinflammatory cytokines, and induce cell-cell interaction between platelets and neutrophils. Thus, under certain conditions, RMPs could play a role in posttransfusion complications through these mechanisms. C ell-derived microparticles (MPs) are membrane vesicles smaller than 1 lm in diameter that are released by various types of cells during cell activation, injury, and apoptosis.1 Release ofMPs is also an integral part of red blood cell (RBC) aging and a prominent feature of the RBC storage lesion. It has been demonstrated that MPs are involved in a broad range of (patho-)physiological processes, such as angiogenesis, inflammation, and coagulation. Therefore, the biological effects and possible clinical relevance of RBCderived MPs (RMPs) need to be clarified. 2-5ABBREVIATION: CXCL-8 5 chemokine C-X-C motif ligand 8; Clinical studies have revealed that elevated levels of circulating RMPs are related to the hypercoagulable state in sickle-cell crisis, venous thromboembolism, and other conditions known to affect coagulation, such as diabetes, cardiovascular disease, and sepsis. [6][7][8][9][10] In addition, it has been observed that patients receiving RBCs are at risk for thrombotic events in a...
LR with CD45 microbeads not only reduces animal usage but also provides a more efficacious method regarding posttransfusion red blood cell recovery and, hence, provides a promising alternative to commonly used methods.
Objective: Several Western European countries and Canada have introduced white blood cell reduction as a universal standard to prevent potential adverse effects of allogeneic blood transfusions. However, there is an ongoing controversy regarding its appropriateness in other countries such as North America. We were interested in the whereabouts of leukocytes following whole blood transfusion in mice to evaluate their potential sites of (adverse) action. Materials and methods:Wildtype C57BL/6 were transfused with non-leukoreduced blood from enhanced green fluorescent protein transgenic C57BL/6-Tg(CAGEGFP) 1 Osb/J mice. Cells were tracked on day 3 and day 5 after transfusion by flow cytometry.Results: Enhanced green fluorescent protein-labeled leukocytes were found in the blood circulation, the myocardium, bone marrow and lung tissue up until day 5, but not in the kidney, the liver or the spleen. Myeloperoxidase activity in the lungs was significantly higher on day 5 when compared to control animals (0.09 ± 0.01% vs. 0.26 ± 0.08%, p=0.047). There was no increase in cytokines. Conclusion:Syngeneic white blood cells survive in the recipient of non-leukoreduced red blood cell units. They circulate in the blood stream and can be found in the bone marrow and the lungs up to five days after transfusion.
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