Skip to main content
Top
Published in: European Journal of Trauma and Emergency Surgery 1/2020

01-02-2020 | Original Article

Microparticles profiling in trauma patients: high level of microparticles induce activation of platelets in vitro

Authors: Michael Caspers, Nadine Schäfer, Matthias Fröhlich, Bertil Bouillon, Manuel Mutschler, Ursula Bauerfeind, Marc Maegele

Published in: European Journal of Trauma and Emergency Surgery | Issue 1/2020

Login to get access

Abstract

Purpose

Trauma-induced coagulopathy (TIC) is recognised as an own clinical entity which includes all components of haemostasis following rapidly tissue injury, hypoperfusion and shock. Microparticles (MP) are known to be released in large quantities from different cell types after trauma. The present study aimed to perform a phenotypic MP profiling after major trauma and to elucidate potential procoagulative function of MP under simulated conditions of lethal triad.

Methods

For MP isolation, 20 trauma patients (median ISS 24) were included. To produce a Standard MP Phenotype Profile after trauma, samples were pooled, extracted and concentrated by using an ultracentrifuge protocol. Specific cell surface markers were measured by flow cytometry. Our Standard MP Phenotype Profile was subsequently added in high and low concentration to an in vitro lethal triad assay, simulating coagulopathy via induced hypothermia, dilution and acidosis. A comprehensive analysis of coagulation function was performed.

Results

Within our Standard MP Phenotype Profile, PDMP (56%) were found as predominant phenotype followed by EDMP (33%) and MDMP (11%). EDMP characterized by CD144, CD62E and Annexin were determined most frequently but also EDMP expressing CD62P. In addition, tissue factor (TF) was expressed on all MP entities (EDMP 63%, PDMP 30%, MDMP 7%). Within our lethal triad simulation assay, the addition of low and high concentrated MP did not cause any significant alteration in standard coagulation assays, coagulation initiation, clot kinetics or stability. Addition of high concentrated MP increased platelet function and P-selectin expression significantly.

Conclusion

Our data confirm the assumption that there is a characteristic MP phenotype pattern in trauma, which may alter haemostatic capacity at least in part mediated via augmenting in primary haemostasis resulting in an improved contribution of platelets to clot formation. There are indications that expression of selectins on MP surface is involved in this activation process, but this pathway needs to be investigated in more detail.
Appendix
Available only for authorised users
Literature
1.
go back to reference Brohi K, Singh J, Heron M, Coats T. Acute traumatic coagulopathy. J Trauma. 2003;54:1127–30.CrossRef Brohi K, Singh J, Heron M, Coats T. Acute traumatic coagulopathy. J Trauma. 2003;54:1127–30.CrossRef
2.
go back to reference Johansson PI, Stensballe J, Rasmussen LS, Ostrowski SR. High circulating adrenaline levels at admission predict increased mortality after trauma. J Trauma Inj Infect Crit Care. 2011;72:1. Johansson PI, Stensballe J, Rasmussen LS, Ostrowski SR. High circulating adrenaline levels at admission predict increased mortality after trauma. J Trauma Inj Infect Crit Care. 2011;72:1.
3.
go back to reference Johansson PI, Stensballe J, Rasmussen LS, Ostrowski SR. A high admission syndecan-1 level, a marker of endothelial glycocalyx degradation, is associated with inflammation, protein C depletion, fibrinolysis, and increased mortality in trauma patients. Ann Surg. 2011;254:194–200.CrossRef Johansson PI, Stensballe J, Rasmussen LS, Ostrowski SR. A high admission syndecan-1 level, a marker of endothelial glycocalyx degradation, is associated with inflammation, protein C depletion, fibrinolysis, and increased mortality in trauma patients. Ann Surg. 2011;254:194–200.CrossRef
4.
go back to reference Ganter MT, Brohi K, Cohen MJ, Shaffer L, Walsh MC, Stahl GL, et al. Role of the alternative pathway in the early complement activation following major trauma. Shock. 2007;28:29–34.CrossRef Ganter MT, Brohi K, Cohen MJ, Shaffer L, Walsh MC, Stahl GL, et al. Role of the alternative pathway in the early complement activation following major trauma. Shock. 2007;28:29–34.CrossRef
6.
go back to reference Evans JA, Van Wessem KJP, McDougall D, Lee KA, Lyons T, Balogh ZJ. Epidemiology of traumatic deaths: Comprehensive population-based assessment. World J Surg. 2010;34:158–63.CrossRef Evans JA, Van Wessem KJP, McDougall D, Lee KA, Lyons T, Balogh ZJ. Epidemiology of traumatic deaths: Comprehensive population-based assessment. World J Surg. 2010;34:158–63.CrossRef
13.
go back to reference Windeløv NA, Johansson PI, Sørensen AM, Perner A, Wanscher M, Larsen CF, et al. Low level of procoagulant platelet microparticles is associated with impaired coagulation and transfusion requirements in trauma patients. J Trauma Acute Care Surg [Internet]. 2014;77:692–700. http://www.ncbi.nlm.nih.gov/pubmed/25494419. Windeløv NA, Johansson PI, Sørensen AM, Perner A, Wanscher M, Larsen CF, et al. Low level of procoagulant platelet microparticles is associated with impaired coagulation and transfusion requirements in trauma patients. J Trauma Acute Care Surg [Internet]. 2014;77:692–700. http://​www.​ncbi.​nlm.​nih.​gov/​pubmed/​25494419.
14.
go back to reference Matijevic N, Wang YWW, Wade CE, Holcomb JB, Cotton BA, Schreiber MA, et al. Cellular microparticle and thrombogram phenotypes in the prospective observational multicenter major trauma transfusion (PROMMTT) study: correlation with coagulopathy. Thromb Res. 2014;134:652–58.CrossRef Matijevic N, Wang YWW, Wade CE, Holcomb JB, Cotton BA, Schreiber MA, et al. Cellular microparticle and thrombogram phenotypes in the prospective observational multicenter major trauma transfusion (PROMMTT) study: correlation with coagulopathy. Thromb Res. 2014;134:652–58.CrossRef
16.
go back to reference Xie RF, Hu P, Li W, Ren YN, Yang J, Yang YM, et al. The effect of platelet-derived microparticles in stored apheresis platelet concentrates on polymorphonuclear leucocyte respiratory burst. Vox Sang. 2014;106:234–41.CrossRef Xie RF, Hu P, Li W, Ren YN, Yang J, Yang YM, et al. The effect of platelet-derived microparticles in stored apheresis platelet concentrates on polymorphonuclear leucocyte respiratory burst. Vox Sang. 2014;106:234–41.CrossRef
17.
go back to reference Gruen RL, Brohi K, Schreiber M, Balogh ZJ, Pitt V, Narayan M, et al. Haemorrhage control in severely injured patients. Lancet. 2012;380:1099–108.CrossRef Gruen RL, Brohi K, Schreiber M, Balogh ZJ, Pitt V, Narayan M, et al. Haemorrhage control in severely injured patients. Lancet. 2012;380:1099–108.CrossRef
18.
go back to reference Fröhlich M, Schäfer N, Caspers M, Böhm JK, Stürmer EK, Bouillon B, et al. Temporal phenotyping of circulating microparticles after trauma: a prospective cohort study. Scand J Trauma Resusc Emerg Med. 2018;26:33.CrossRef Fröhlich M, Schäfer N, Caspers M, Böhm JK, Stürmer EK, Bouillon B, et al. Temporal phenotyping of circulating microparticles after trauma: a prospective cohort study. Scand J Trauma Resusc Emerg Med. 2018;26:33.CrossRef
20.
go back to reference Pasquet JM, Toti F, Nurden AT, Dachary-Prigent J. Procoagulant activity and active calpain in platelet-derived microparticles. Thromb Res. 1996;82:509–22.CrossRef Pasquet JM, Toti F, Nurden AT, Dachary-Prigent J. Procoagulant activity and active calpain in platelet-derived microparticles. Thromb Res. 1996;82:509–22.CrossRef
21.
go back to reference Bevers EM, Comfurius P, Zwaal RFA. Platelet procoagulant activity: physiological significance and mechanisms of exposure. J Voice. 1991;5:146–54. Bevers EM, Comfurius P, Zwaal RFA. Platelet procoagulant activity: physiological significance and mechanisms of exposure. J Voice. 1991;5:146–54.
22.
23.
go back to reference Khan MMH, Hattori T, Niewiarowski S, Edmunds LH, Colman RW. Truncated and microparticle-free soluble tissue factor bound to peripheral monocytes preferentially activate factor VII. Thromb Haemost. 2006;95:462–8.CrossRef Khan MMH, Hattori T, Niewiarowski S, Edmunds LH, Colman RW. Truncated and microparticle-free soluble tissue factor bound to peripheral monocytes preferentially activate factor VII. Thromb Haemost. 2006;95:462–8.CrossRef
24.
go back to reference Robert S, Poncelet P, Lacroix R, Arnaud L, Giraudo L, Hauchard A, et al. Standardization of platelet-derived microparticle counting using calibrated beads and a Cytomics FC500 routine flow cytometer: a first step towards multicenter studies? J Thromb Haemost. 2009;7:190–7.CrossRef Robert S, Poncelet P, Lacroix R, Arnaud L, Giraudo L, Hauchard A, et al. Standardization of platelet-derived microparticle counting using calibrated beads and a Cytomics FC500 routine flow cytometer: a first step towards multicenter studies? J Thromb Haemost. 2009;7:190–7.CrossRef
25.
go back to reference Enjeti A, Lincz L, Seldon M. Microparticles in health and disease. Semin Thromb Hemost. 2008;34:683–91.CrossRef Enjeti A, Lincz L, Seldon M. Microparticles in health and disease. Semin Thromb Hemost. 2008;34:683–91.CrossRef
26.
go back to reference Combes V, Simon AC, Grau GE, Arnoux D, Camoin L, Sabatier F, et al. In vitro generation of endothelial microparticles and possible prothrombotic activity in patients with lupus anticoagulant. J Clin Invest. 1999;104:93–102.CrossRef Combes V, Simon AC, Grau GE, Arnoux D, Camoin L, Sabatier F, et al. In vitro generation of endothelial microparticles and possible prothrombotic activity in patients with lupus anticoagulant. J Clin Invest. 1999;104:93–102.CrossRef
29.
go back to reference Haubold K, Rink M, Spath B, Friedrich M, Chun FKH, Marx G, et al. Tissue factor procoagulant activity of plasma microparticles is increased in patients with early-stage prostate cancer. Thromb Haemost. 2009;101:1147–55.CrossRef Haubold K, Rink M, Spath B, Friedrich M, Chun FKH, Marx G, et al. Tissue factor procoagulant activity of plasma microparticles is increased in patients with early-stage prostate cancer. Thromb Haemost. 2009;101:1147–55.CrossRef
30.
go back to reference Burton JO, Hamali HA, Singh R, Abbasian N, Parsons R, Patel AK, et al. Elevated levels of procoagulant plasma microvesicles in dialysis patients. PLoS One. 2013. Burton JO, Hamali HA, Singh R, Abbasian N, Parsons R, Patel AK, et al. Elevated levels of procoagulant plasma microvesicles in dialysis patients. PLoS One. 2013.
31.
go back to reference Owens AP, MacKman N. Microparticles in hemostasis and thrombosis. Circ Res. 2011;108:1284–97.CrossRef Owens AP, MacKman N. Microparticles in hemostasis and thrombosis. Circ Res. 2011;108:1284–97.CrossRef
32.
go back to reference Meng ZH, Wolberg AS, Monroe DM, Hoffman M. The effect of temperature and pH on the activity of factor VIIa: implications for the efficacy of high-dose factor VIIa in hypothermic and acidotic patients. J. Trauma. 2003;55:886–91.CrossRef Meng ZH, Wolberg AS, Monroe DM, Hoffman M. The effect of temperature and pH on the activity of factor VIIa: implications for the efficacy of high-dose factor VIIa in hypothermic and acidotic patients. J. Trauma. 2003;55:886–91.CrossRef
33.
go back to reference Myers DD, Hawley AE, Farris DM, Wrobleski SK, Thanaporn P, Schaub RG, et al. P-selectin and leukocyte microparticles are associated with venous thrombogenesis. J Vasc Surg. 2003;38:1075–89.CrossRef Myers DD, Hawley AE, Farris DM, Wrobleski SK, Thanaporn P, Schaub RG, et al. P-selectin and leukocyte microparticles are associated with venous thrombogenesis. J Vasc Surg. 2003;38:1075–89.CrossRef
34.
go back to reference Furie B, Furie BC, Flaumenhaft R. A journey with platelet P-selectin: the molecular basis of granule secretion, signalling and cell adhesion. Thromb Haemost. 2001;86:214–21.CrossRef Furie B, Furie BC, Flaumenhaft R. A journey with platelet P-selectin: the molecular basis of granule secretion, signalling and cell adhesion. Thromb Haemost. 2001;86:214–21.CrossRef
Metadata
Title
Microparticles profiling in trauma patients: high level of microparticles induce activation of platelets in vitro
Authors
Michael Caspers
Nadine Schäfer
Matthias Fröhlich
Bertil Bouillon
Manuel Mutschler
Ursula Bauerfeind
Marc Maegele
Publication date
01-02-2020
Publisher
Springer Berlin Heidelberg
Published in
European Journal of Trauma and Emergency Surgery / Issue 1/2020
Print ISSN: 1863-9933
Electronic ISSN: 1863-9941
DOI
https://doi.org/10.1007/s00068-019-01111-7

Other articles of this Issue 1/2020

European Journal of Trauma and Emergency Surgery 1/2020 Go to the issue