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

Abstract

BackgroundAfter 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.MethodsBlood 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).ResultsTwenty 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.DiscussionIn 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.ConclusionIn 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.

Divergent enhancement of in vitro induced coagulopathy by microparticle subtypes

“…As recently published by our group, there is a positive correlation between injury severity and MP concentration after trauma likely reaching high quantities inducing procoagulative effects [16]. Our in vitro experimental setup indicates that under LT conditions MP promote procoagulative function by different pathways based on their cellular origin.…”

“…Special emphasis was given on the analysis of selected MP on blood coagulation with particular focus on PDMP and EDMP. Both MP subtypes had been reported to be released in high quantities in patients who sustained major traumatic injuries indicating that these particles might be involved in regulating blood coagulation after trauma [16,17,21,22]. With this study we demonstrated for the rst time a divergent mechanism of action on coagulation originating from MP with different parental cells.…”

“…In contrast, small circulating microparticles (MP), with diverse cellular origin exhibit different function supporting coagulation at the boundary of cellular-and plasmatic-driven coagulation. Beside plateletderived MP (PDMP), own investigations also revealed endothelial-derived MP (EDMP) as crucial players in the trauma setting as being associated with improved coagulation parameters [16,17]. However, to date it is still less understood how different cell-speci c MP physiologically functionalize under traumainduced coagulation disturbances.…”

Platelets and Fibrinogen: Emerging Complexity in Trauma-Induced Coagulopathy

“…These microparticles of platelet cell membrane are procoagulant, 58,59 and their levels in circulation increase after injury. 60 In one study, patients with only modest increases in the PMP level had a higher incidence of coagulopathy and higher blood transfusion requirement, 61 though another large study found no clear association. 62 These heterogeneous findings could arise from the existence of multiple PMP subpopulations with differing phenotypic effects.…”

Plasmatic and cell-based enhancement of&nbsp;in vitro&nbsp;induced coagulopathy by microparticles originated from platelets and endothelial cells

“…Special emphasis was given to the analysis of selected MP on blood coagulation with a particular focus on PDMP and EDMP. Both MP subtypes had been reported to be released in high quantities in patients who sustained major traumatic injuries indicating that these particles might be involved in regulating blood coagulation after trauma [19,25,31,32]. With this study we demonstrated for the rst time a divergent mechanism of action on coagulation originating from MP with different parental cells.…”