The “Fondation Humanitaire de la Croix-Rouge Suisse” financially supported this study.
Red blood cell–derived microparticles isolated from blood units initiate and propagate thrombin generation
Version of Record online: 11 DEC 2012
© 2012 American Association of Blood Banks
Volume 53, Issue 8, pages 1744–1754, August 2013
How to Cite
Rubin, O., Delobel, J., Prudent, M., Lion, N., Kohl, K., Tucker, E. I., Tissot, J.-D. and Angelillo-Scherrer, A. (2013), Red blood cell–derived microparticles isolated from blood units initiate and propagate thrombin generation. Transfusion, 53: 1744–1754. doi: 10.1111/trf.12008
- Issue online: 8 AUG 2013
- Version of Record online: 11 DEC 2012
- Manuscript Accepted: 1 OCT 2012
- Manuscript Revised: 28 SEP 2012
- Manuscript Received: 21 MAY 2012
- Fondation Humanitaire de la Croix-Rouge Suisse
Red blood cell–derived microparticles (RMPs) are small phospholipid vesicles shed from RBCs in blood units, where they accumulate during storage. Because microparticles are bioactive, it could be suggested that RMPs are mediators of posttransfusion complications or, on the contrary, constitute a potential hemostatic agent.
Study Design and Methods
This study was performed to establish the impact on coagulation of RMPs isolated from blood units. Using calibrated automated thrombography, we investigated whether RMPs affect thrombin generation (TG) in plasma.
We found that RMPs were not only able to increase TG in plasma in the presence of a low exogenous tissue factor (TF) concentration, but also to initiate TG in plasma in absence of exogenous TF. TG induced by RMPs in the absence of exogenous TF was neither affected by the presence of blocking anti-TF nor by the absence of Factor (F)VII. It was significantly reduced in plasma deficient in FVIII or F IX and abolished in FII-, FV-, FX-, or FXI-deficient plasma. TG was also totally abolished when anti-XI 01A6 was added in the sample. Finally, neither Western blotting, flow cytometry, nor immunogold labeling allowed the detection of traces of TF antigen. In addition, RMPs did not comprise polyphosphate, an important modulator of coagulation.
Taken together, our data show that RMPs have FXI-dependent procoagulant properties and are able to initiate and propagate TG. The anionic surface of RMPs might be the site of FXI-mediated TG amplification and intrinsic tenase and prothrombinase complex assembly.