Microparticles from stored red blood cells enhance procoagulant and proinflammatory activity

• Published in: Transfusion (Philadelphia, Pa.) Vol. 57; no. 11; pp. 2701 - 2711
• Main Authors: Fischer, Dania, Büssow, Julian, Meybohm, Patrick, Weber, Christian Friedrich, Zacharowski, Kai, Urbschat, Anja, Müller, Markus Matthias, Jennewein, Carla
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.11.2017
• Subjects: Blood; Blood Coagulation; Blood platelets; Blood Preservation; Blood transfusion; Cell Communication; Cell-Derived Microparticles - physiology; Clotting; Coagulation; Complications; Cytokines; Cytometry; Erythrocytes; Erythrocytes - cytology; Erythrocytes - ultrastructure; Flow cytometry; Gene expression; Humans; Immunoassays; Inflammation; Inflammation - etiology; Interleukin 1; Interleukin 6; Interleukin-6 - blood; Interleukin-8 - blood; Leukocytes (neutrophilic); Microparticles; Monocytes; Monocytes - metabolism; Morbidity; Neutrophils; P-selectin; PAC1 protein; Platelet Activation; Platelets; Polymerase chain reaction; Ribonucleic acid; RNA; RNA, Messenger - blood; Signaling; Thromboplastin - genetics; Thromboplastin - metabolism; Thrombosis - etiology; Tissue factor; Transfusion; Transfusion Reaction
• ISSN: 0041-1132; 1537-2995
• DOI: 10.1111/trf.14268

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 time‐dependent and concentration‐dependent manner. There was a significant induction of interleukin‐1β 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 post‐transfusion complications through these mechanisms.