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Published in: Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine 1/2018

Open Access 01-12-2018 | Original research

Temporal phenotyping of circulating microparticles after trauma: a prospective cohort study

Authors: Matthias Fröhlich, Nadine Schäfer, Michael Caspers, Julia K. Böhm, Ewa K. Stürmer, Bertil Bouillon, Marc Maegele

Published in: Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine | Issue 1/2018

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Abstract

Background

After severe polytrauma the dynamic process of coagulation may deteriorate towards a trauma-induced coagulopathy (TIC) promoting a dramatic increase in morbidity and mortality. Recent evidence suggests that microparticles (MPs) play a pivotal role at the interface between cellular and plasmatic coagulation systems. However, the impact of MPs on functional coagulation has not been clarified yet in the setting of traumatic injuries. We assessed the temporal patterns of circulating MP concentrations including their cellular origin in the context of clinical presentation and global coagulation assays.

Methods

Blood samples from 22 consecutive polytrauma patients (ISS ≥16) from 2015 were collected at hospital admission, after 24 and 72 h and compared to those from healthy individuals and minor injured patients with isolated extremity fractures. Flow cytometry (BD Accuri C6; Heidelberg/Germany) was used to determine MP concentrations and cellular origin using cell-specific markers (platelet derived (PDMP): CD42b+, CD61+, CD62p+; endothelial cell derived (EDMP): CD144+, CD62e+, CD144+/62e+). Results were correlated with clinical data and results from viscoelastic testing (ROTEM).

Results

Twenty two polytrauma patients (17 males, agemedian 60 yrs) with a median ISS 26.5 (IQR 14.5) were assessed. PDMP and EDMP concentrations increased significantly in polytrauma patients as compared to healthy individuals and minor injured patients. MP concentrations correlated with injury severity (CD144+: ρsp = 0.79, p < 0.001; CD42b+: ρsp = 0.61, p < 0.001). EDMP displayed a negative correlation with aPTT (CD144/62e+, ρsp = − 0.55, p < 0.05), INR (CD144/62e+, ρsp = − 0.61, p < 0.05) and ROTEM-INTEM CT (CD144/62e+, ρsp = − 0.68, p < 0.05) reflecting increased dynamics of clot formation and an overall procoagulative effect. Additionally, EDMP showed a negative association with FIBTEM values (10 min amplitude, maximum clot firmness) indicating a fibrinolytic potential.

Discussion

In a small cohort, analysing most severly injured patients, the association of increased MP levels and altered coagulation parameters could be demonstrated. However, these findings are based on correlation analysis, which do not enable causel evidence. Therefore, further in-vitro studies are needed analysing the underlying pathomechanisms.

Conclusion

In conclusion, this study could demonstrate that PDMP and EDMP levels increase significantly following polytrauma correlating with injury severity. Although severe coagulopathy was not observed, EDMP levels were associated with improved coagulation parameters suggesting their essential role for regulating blood coagulation after trauma.
Literature
1.
go back to reference Wohlauer MV, Moore EE, Thomas S, Sauaia A, Evans E, Harr J, Silliman CC, Ploplis V, Castellino FJ, Walsh M. Early platelet dysfunction: an unrecognized role in the acute coagulopathy of trauma. J Am Coll Surg. 2012;214(5):739–46.CrossRefPubMedPubMedCentral Wohlauer MV, Moore EE, Thomas S, Sauaia A, Evans E, Harr J, Silliman CC, Ploplis V, Castellino FJ, Walsh M. Early platelet dysfunction: an unrecognized role in the acute coagulopathy of trauma. J Am Coll Surg. 2012;214(5):739–46.CrossRefPubMedPubMedCentral
2.
go back to reference Berckmans RJ, Nieuwland R, Boing AN, Romijn FP, Hack CE, Sturk A. Cell-derived microparticles circulate in healthy humans and support low grade thrombin generation. Thromb Haemost. 2001;85(4):639–46.CrossRefPubMed Berckmans RJ, Nieuwland R, Boing AN, Romijn FP, Hack CE, Sturk A. Cell-derived microparticles circulate in healthy humans and support low grade thrombin generation. Thromb Haemost. 2001;85(4):639–46.CrossRefPubMed
3.
go back to reference Hargett LA, Bauer NN. On the origin of microparticles: From “platelet dust” to mediators of intercellular communication. Pulm Circ. 2013;3(2):329–40.CrossRefPubMedPubMedCentral Hargett LA, Bauer NN. On the origin of microparticles: From “platelet dust” to mediators of intercellular communication. Pulm Circ. 2013;3(2):329–40.CrossRefPubMedPubMedCentral
4.
go back to reference Burnier L, Fontana P, Kwak BR, Angelillo-Scherrer A. Cell-derived microparticles in haemostasis and vascular medicine. Thromb Haemost. 2009;101(3):439–51.PubMed Burnier L, Fontana P, Kwak BR, Angelillo-Scherrer A. Cell-derived microparticles in haemostasis and vascular medicine. Thromb Haemost. 2009;101(3):439–51.PubMed
5.
go back to reference Jy W, Jimenez JJ, Mauro LM, Horstman LL, Cheng P, Ahn ER, Bidot CJ, Ahn YS. Endothelial microparticles induce formation of platelet aggregates via a von Willebrand factor/ristocetin dependent pathway, rendering them resistant to dissociation. J Thromb Haemost. 2005;3(6):1301–8.CrossRefPubMed Jy W, Jimenez JJ, Mauro LM, Horstman LL, Cheng P, Ahn ER, Bidot CJ, Ahn YS. Endothelial microparticles induce formation of platelet aggregates via a von Willebrand factor/ristocetin dependent pathway, rendering them resistant to dissociation. J Thromb Haemost. 2005;3(6):1301–8.CrossRefPubMed
7.
go back to reference Connor DE, Exner T, Ma DD, Joseph JE. The majority of circulating platelet-derived microparticles fail to bind annexin V, lack phospholipid-dependent procoagulant activity and demonstrate greater expression of glycoprotein Ib. Thromb Haemost. 2010;103(5):1044–52.CrossRefPubMed Connor DE, Exner T, Ma DD, Joseph JE. The majority of circulating platelet-derived microparticles fail to bind annexin V, lack phospholipid-dependent procoagulant activity and demonstrate greater expression of glycoprotein Ib. Thromb Haemost. 2010;103(5):1044–52.CrossRefPubMed
8.
go back to reference Sinauridze EI, Kireev DA, Popenko NY, Pichugin AV, Panteleev MA, Krymskaya OV, Ataullakhanov FI. Platelet microparticle membranes have 50- to 100-fold higher specific procoagulant activity than activated platelets. Thromb Haemost. 2007;97(3):425–34.CrossRefPubMed Sinauridze EI, Kireev DA, Popenko NY, Pichugin AV, Panteleev MA, Krymskaya OV, Ataullakhanov FI. Platelet microparticle membranes have 50- to 100-fold higher specific procoagulant activity than activated platelets. Thromb Haemost. 2007;97(3):425–34.CrossRefPubMed
9.
go back to reference Curry N, Raja A, Beavis J, Stanworth S, Harrison P. Levels of procoagulant microvesicles are elevated after traumatic injury and platelet microvesicles are negatively correlated with mortality. J Extracell Vesicles. 2014;3:25625.CrossRefPubMed Curry N, Raja A, Beavis J, Stanworth S, Harrison P. Levels of procoagulant microvesicles are elevated after traumatic injury and platelet microvesicles are negatively correlated with mortality. J Extracell Vesicles. 2014;3:25625.CrossRefPubMed
10.
go back to reference Windelov NA, Johansson PI, Sorensen AM, Perner A, Wanscher M, Larsen CF, Ostrowski SR, Rasmussen LS. Low level of procoagulant platelet microparticles is associated with impaired coagulation and transfusion requirements in trauma patients. J Trauma Acute Care Surg. 2014;77(5):692–700.CrossRefPubMed Windelov NA, Johansson PI, Sorensen AM, Perner A, Wanscher M, Larsen CF, Ostrowski SR, Rasmussen LS. Low level of procoagulant platelet microparticles is associated with impaired coagulation and transfusion requirements in trauma patients. J Trauma Acute Care Surg. 2014;77(5):692–700.CrossRefPubMed
11.
go back to reference Matijevic N, Wang YW, Wade CE, Holcomb JB, Cotton BA, Schreiber MA, Muskat P, Fox EE, Del Junco DJ, Cardenas JC, et al. Cellular microparticle and thrombogram phenotypes in the Prospective Observational Multicenter Major Trauma Transfusion (PROMMTT) study: correlation with coagulopathy. Thromb Res. 2014;134(3):652–8.CrossRefPubMedPubMedCentral Matijevic N, Wang YW, Wade CE, Holcomb JB, Cotton BA, Schreiber MA, Muskat P, Fox EE, Del Junco DJ, Cardenas JC, et al. Cellular microparticle and thrombogram phenotypes in the Prospective Observational Multicenter Major Trauma Transfusion (PROMMTT) study: correlation with coagulopathy. Thromb Res. 2014;134(3):652–8.CrossRefPubMedPubMedCentral
12.
go back to reference Balvers K, Curry N, Kleinveld DJ, Boing AN, Nieuwland R, Goslings JC, Juffermans NP. Endogenous microparticles drive the proinflammatory host immune response in severely injured trauma patients. Shock. 2015;43(4):317–21.CrossRefPubMed Balvers K, Curry N, Kleinveld DJ, Boing AN, Nieuwland R, Goslings JC, Juffermans NP. Endogenous microparticles drive the proinflammatory host immune response in severely injured trauma patients. Shock. 2015;43(4):317–21.CrossRefPubMed
13.
go back to reference Lacroix R, Judicone C, Mooberry M, Boucekine M, Key NS, Dignat-George F, The ISSCW. Standardization of pre-analytical variables in plasma microparticle determination: results of the International Society on Thrombosis and Haemostasis SSC Collaborative workshop. J Thromb Haemost. 2013. https://doi.org/10.1111/jth.12207. Lacroix R, Judicone C, Mooberry M, Boucekine M, Key NS, Dignat-George F, The ISSCW. Standardization of pre-analytical variables in plasma microparticle determination: results of the International Society on Thrombosis and Haemostasis SSC Collaborative workshop. J Thromb Haemost. 2013. https://​doi.​org/​10.​1111/​jth.​12207.
14.
go back to reference Jy W, Horstman LL, Jimenez JJ, Ahn YS, Biro E, Nieuwland R, Sturk A, Dignat-George F, Sabatier F, Camoin-Jau L, et al. Measuring circulating cell-derived microparticles. J Thromb Haemost. 2004;2(10):1842–51.CrossRefPubMed Jy W, Horstman LL, Jimenez JJ, Ahn YS, Biro E, Nieuwland R, Sturk A, Dignat-George F, Sabatier F, Camoin-Jau L, et al. Measuring circulating cell-derived microparticles. J Thromb Haemost. 2004;2(10):1842–51.CrossRefPubMed
15.
go back to reference Enjeti AK, Lincz LF, Seldon M. Microparticles in health and disease. Semin Thromb Hemost. 2008;34(7):683–91.CrossRefPubMed Enjeti AK, Lincz LF, Seldon M. Microparticles in health and disease. Semin Thromb Hemost. 2008;34(7):683–91.CrossRefPubMed
16.
go back to reference Park MS, Owen BA, Ballinger BA, Sarr MG, Schiller HJ, Zietlow SP, Jenkins DH, Ereth MH, Owen WG, Heit JA. Quantification of hypercoagulable state after blunt trauma: microparticle and thrombin generation are increased relative to injury severity, while standard markers are not. Surgery. 2012;151(6):831–6.CrossRefPubMedPubMedCentral Park MS, Owen BA, Ballinger BA, Sarr MG, Schiller HJ, Zietlow SP, Jenkins DH, Ereth MH, Owen WG, Heit JA. Quantification of hypercoagulable state after blunt trauma: microparticle and thrombin generation are increased relative to injury severity, while standard markers are not. Surgery. 2012;151(6):831–6.CrossRefPubMedPubMedCentral
17.
go back to reference Awad HA, Tantawy AA, El-Farrash RA, Ismail EA, Youssif NM. CD144+ endothelial microparticles as a marker of endothelial injury in neonatal ABO blood group incompatibility. Blood Transfus. 2014;12(2):250–9.PubMedPubMedCentral Awad HA, Tantawy AA, El-Farrash RA, Ismail EA, Youssif NM. CD144+ endothelial microparticles as a marker of endothelial injury in neonatal ABO blood group incompatibility. Blood Transfus. 2014;12(2):250–9.PubMedPubMedCentral
19.
go back to reference Combes V, Simon AC, Grau GE, Arnoux D, Camoin L, Sabatier F, Mutin M, Sanmarco M, Sampol J, Dignat-George F. In vitro generation of endothelial microparticles and possible prothrombotic activity in patients with lupus anticoagulant. J Clin Invest. 1999;104(1):93–102.CrossRefPubMedPubMedCentral Combes V, Simon AC, Grau GE, Arnoux D, Camoin L, Sabatier F, Mutin M, Sanmarco M, Sampol J, Dignat-George F. In vitro generation of endothelial microparticles and possible prothrombotic activity in patients with lupus anticoagulant. J Clin Invest. 1999;104(1):93–102.CrossRefPubMedPubMedCentral
20.
go back to reference Lacroix R, Plawinski L, Robert S, Doeuvre L, Sabatier F, Martinez de Lizarrondo S, Mezzapesa A, Anfosso F, Leroyer AS, Poullin P, et al. Leukocyte- and endothelial-derived microparticles: a circulating source for fibrinolysis. Haematologica. 2012;97(12):1864–72.CrossRefPubMedPubMedCentral Lacroix R, Plawinski L, Robert S, Doeuvre L, Sabatier F, Martinez de Lizarrondo S, Mezzapesa A, Anfosso F, Leroyer AS, Poullin P, et al. Leukocyte- and endothelial-derived microparticles: a circulating source for fibrinolysis. Haematologica. 2012;97(12):1864–72.CrossRefPubMedPubMedCentral
21.
go back to reference Perez-Casal M, Downey C, Fukudome K, Marx G, Toh CH. Activated protein C induces the release of microparticle-associated endothelial protein C receptor. Blood. 2005;105(4):1515–22.CrossRefPubMed Perez-Casal M, Downey C, Fukudome K, Marx G, Toh CH. Activated protein C induces the release of microparticle-associated endothelial protein C receptor. Blood. 2005;105(4):1515–22.CrossRefPubMed
22.
go back to reference Lacroix R, Dignat-George F. Microparticles as a circulating source of procoagulant and fibrinolytic activities in the circulation. Thromb Res. 2012;129(Suppl 2):S27–9.CrossRefPubMed Lacroix R, Dignat-George F. Microparticles as a circulating source of procoagulant and fibrinolytic activities in the circulation. Thromb Res. 2012;129(Suppl 2):S27–9.CrossRefPubMed
23.
go back to reference Rossaint R, Bouillon B, Cerny V, Coats TJ, Duranteau J, Fernandez-Mondejar E, Filipescu D, Hunt BJ, Komadina R, Nardi G, et al. The European guideline on management of major bleeding and coagulopathy following trauma: fourth edition. Crit Care. 2016;20:100.CrossRefPubMedPubMedCentral Rossaint R, Bouillon B, Cerny V, Coats TJ, Duranteau J, Fernandez-Mondejar E, Filipescu D, Hunt BJ, Komadina R, Nardi G, et al. The European guideline on management of major bleeding and coagulopathy following trauma: fourth edition. Crit Care. 2016;20:100.CrossRefPubMedPubMedCentral
24.
go back to reference Taniguchi Y, Tanaka H, Luis EJ, Sakai K, Kumode T, Sano K, Serizawa K, Rai S, Morita Y, Hanamoto H, et al. Elevated plasma levels of procoagulant microparticles are a novel risk factor for thrombosis in patients with myeloproliferative neoplasms. Int J Hematol. 2017;106(5):691–703.CrossRefPubMed Taniguchi Y, Tanaka H, Luis EJ, Sakai K, Kumode T, Sano K, Serizawa K, Rai S, Morita Y, Hanamoto H, et al. Elevated plasma levels of procoagulant microparticles are a novel risk factor for thrombosis in patients with myeloproliferative neoplasms. Int J Hematol. 2017;106(5):691–703.CrossRefPubMed
25.
go back to reference Mege D, Crescence L, Ouaissi M, Sielezneff I, Guieu R, Dignat-George F, Dubois C, Panicot-Dubois L. Fibrin-bearing microparticles: marker of thrombo-embolic events in pancreatic and colorectal cancers. Oncotarget. 2017;8(57):97394–406.CrossRefPubMedPubMedCentral Mege D, Crescence L, Ouaissi M, Sielezneff I, Guieu R, Dignat-George F, Dubois C, Panicot-Dubois L. Fibrin-bearing microparticles: marker of thrombo-embolic events in pancreatic and colorectal cancers. Oncotarget. 2017;8(57):97394–406.CrossRefPubMedPubMedCentral
26.
go back to reference Shaver CM, Woods J, Clune JK, Grove BS, Wickersham NE, McNeil JB, Shemancik G, Ware LB, Bastarache JA. Circulating microparticle levels are reduced in patients with ARDS. Crit Care. 2017;21(1):120.CrossRefPubMedPubMedCentral Shaver CM, Woods J, Clune JK, Grove BS, Wickersham NE, McNeil JB, Shemancik G, Ware LB, Bastarache JA. Circulating microparticle levels are reduced in patients with ARDS. Crit Care. 2017;21(1):120.CrossRefPubMedPubMedCentral
27.
go back to reference Park MS, Xue A, Spears GM, Halling TM, Ferrara MJ, Kuntz MM, Dhillon SK, Jenkins DH, Harmsen WS, Ballman KV, et al. Thrombin generation and procoagulant microparticle profiles after acute trauma: A prospective cohort study. J Trauma Acute Care Surg. 2015;79(5):726–31.CrossRefPubMedPubMedCentral Park MS, Xue A, Spears GM, Halling TM, Ferrara MJ, Kuntz MM, Dhillon SK, Jenkins DH, Harmsen WS, Ballman KV, et al. Thrombin generation and procoagulant microparticle profiles after acute trauma: A prospective cohort study. J Trauma Acute Care Surg. 2015;79(5):726–31.CrossRefPubMedPubMedCentral
Metadata
Title
Temporal phenotyping of circulating microparticles after trauma: a prospective cohort study
Authors
Matthias Fröhlich
Nadine Schäfer
Michael Caspers
Julia K. Böhm
Ewa K. Stürmer
Bertil Bouillon
Marc Maegele
Publication date
01-12-2018
Publisher
BioMed Central
DOI
https://doi.org/10.1186/s13049-018-0499-9

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