Cellular microparticle and thrombogram phenotypes in the Prospective Observational Multicenter Major Trauma Transfusion (PROMMTT) study: correlation with coagulopathy.

Abstract

BACKGROUND:

Trauma-induced coagulopathy following severe injury is associated with increased bleeding and mortality. Injury may result in alteration of cellular phenotypes and release of cell-derived microparticles (MP). Circulating MPs are procoagulant and support thrombin generation (TG) and clotting. We evaluated MP and TG phenotypes in severely injured patients at admission, in relation to coagulopathy and bleeding.

METHODS:

As part of the Prospective Observational Multicenter Major Trauma Transfusion (PROMMTT) study, research blood samples were obtained from 180 trauma patients requiring transfusions at 5 participating centers. Twenty five healthy controls and 40 minimally injured patients were analyzed for comparisons. Laboratory criteria for coagulopathy was activated partial thromboplastin time (APTT) ≥ 35 sec. Samples were analyzed by Calibrated Automated Thrombogram to assess TG, and by flow cytometry for MP phenotypes [platelet (PMP), erythrocyte (RMP), leukocyte (LMP), endothelial (EMP), tissue factor (TFMP), and Annexin V positive (AVMP)].

RESULTS:

21.7% of patients were coagulopathic with the median (IQR) APTT of 44 sec (37, 53), and an Injury Severity Score of 26 (17, 35). Compared to controls, patients had elevated EMP, RMP, LMP, and TFMP (all p<0.001), and enhanced TG (p<0.0001). However, coagulopathic PROMMTT patients had significantly lower PMP, TFMP, and TG, higher substantial bleeding, and higher mortality compared to non-coagulopathic patients (all p<0.001).

CONCLUSIONS:

Cellular activation and enhanced TG are predominant after trauma and independent of injury severity. Coagulopathy was associated with lower thrombin peak and rate compared to non-coagulopathic patients, while lower levels of TF-bearing PMPs were associated with substantial bleeding.

• Authors: Nena Matijevic, Yao-Wei W Wang, Charles E Wade, John B Holcomb, Bryan A Cotton, Martin A Schreiber, Peter Muskat, Erin E Fox, Deborah J Del Junco, Jessica C Cardenas, Mohammad H Rahbar, Mitchell Jay Cohen, PROMMTT Study Group
• Journal: Thrombosis research (Thromb Res) Vol. 134 Issue 3 Pg. 652-8 (Sep 2014) ISSN: 1879-2472 [Electronic] United States
• PMID: 25086657 (Publication Type: Journal Article, Multicenter Study, Observational Study, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: Copyright © 2014 Elsevier Ltd. All rights reserved.

Chemical References

• Biomarkers
• Thromboplastin
• Thrombin

Topics

• Adult
• Biomarkers (blood)
• Blood Coagulation
• Blood Coagulation Disorders (blood, diagnosis, etiology, mortality, therapy)
• Blood Transfusion
• Cell-Derived Microparticles (metabolism)
• Female
• Hemorrhage (blood, diagnosis, etiology, mortality)
• Humans
• Injury Severity Score
• Male
• Middle Aged
• Partial Thromboplastin Time
• Phenotype
• Predictive Value of Tests
• Prospective Studies
• Risk Factors
• Thrombelastography
• Thrombin (metabolism)
• Thromboplastin (metabolism)
• United States
• Wounds and Injuries (complications, diagnosis, mortality)
• Young Adult