The pathophysiology of acute traumatic coagulopathy and the diagnosis of disseminated intravascular coagulation for trauma patients in acute phase

Abstract Background Major trauma is a leading cause of morbidity and mortality worldwide with hemorrhage accounting for 40% of deaths. Acute traumatic coagulopathy exacerbates bleeding, but controversy remains over the degree to which inhibition of procoagulant pathways (anticoagulation), fibrinogen loss, and fibrinolysis drive the pathologic process. Through a combination of experimental study in a murine model of trauma hemorrhage and human observation, the authors’ objective was to determine the predominant pathophysiology of acute traumatic coagulopathy. Methods First, a prospective cohort study of 300 trauma patients admitted to a single level 1 trauma center with blood samples collected on arrival was performed. Second, a murine model of acute traumatic coagulopathy with suppressed protein C activation via genetic mutation of thrombomodulin was used. In both studies, analysis for coagulation screen, activated protein C levels, and rotational thromboelastometry (ROTEM) was performed. Results In patients with acute traumatic coagulopathy, the authors have demonstrated elevated activated protein C levels with profound fibrinolytic activity and early depletion of fibrinogen. Procoagulant pathways were only minimally inhibited with preservation of capacity to generate thrombin. Compared to factors V and VIII, proteases that do not undergo activated protein C–mediated cleavage were reduced but maintained within normal levels. In transgenic mice with reduced capacity to activate protein C, both fibrinolysis and fibrinogen depletion were significantly attenuated. Other recognized drivers of coagulopathy were associated with less significant perturbations of coagulation. Conclusions Activated protein C–associated fibrinolysis and fibrinogenolysis, rather than inhibition of procoagulant pathways, predominate in acute traumatic coagulopathy. In combination, these findings suggest a central role for the protein C pathway in acute traumatic coagulopathy and provide new translational opportunities for management of major trauma hemorrhage.

Download Full-text

Disseminated intravascular coagulation immediately after trauma predicts a poor prognosis in severely injured patients

Scientific Reports ◽

10.1038/s41598-021-90492-0 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Takeshi Wada ◽

Atsushi Shiraishi ◽

Satoshi Gando ◽

Kazuma Yamakawa ◽

Seitaro Fujishima ◽

...

Keyword(s):

Disseminated Intravascular Coagulation ◽

Survival Probability ◽

Poor Prognosis ◽

Massive Transfusion ◽

Late Phase ◽

Hospital Death ◽

Trauma Patients ◽

Severely Injured ◽

Cross Sectional ◽

Intravascular Coagulation

AbstractTrauma patients die from massive bleeding due to disseminated intravascular coagulation (DIC) with a fibrinolytic phenotype in the early phase, which transforms to DIC with a thrombotic phenotype in the late phase of trauma, contributing to the development of multiple organ dysfunction syndrome (MODS) and a consequently poor outcome. This is a sub-analysis of a multicenter prospective descriptive cross-sectional study on DIC to evaluate the effect of a DIC diagnosis on the survival probability and predictive performance of DIC scores for massive transfusion, MODS, and hospital death in severely injured trauma patients. A DIC diagnosis on admission was associated with a lower survival probability (Log Rank P < 0.001), higher frequency of massive transfusion and MODS and a higher mortality rate than no such diagnosis. The DIC scores at 0 and 3 h significantly predicted massive transfusion, MODS, and hospital death. Markers of thrombin and plasmin generation and fibrinolysis inhibition also showed a good predictive ability for these three items. In conclusion, a DIC diagnosis on admission was associated with a low survival probability. DIC scores obtained immediately after trauma predicted a poor prognosis of severely injured trauma patients.

Download Full-text

424 A SIMPLE DISSEMINATED INTRAVASCULAR COAGULATION SCORE PREDICTS OUTCOME IN TRAUMA PATIENTS

Journal of Investigative Medicine ◽

10.2310/6650.2005.00006.423 ◽

2005 ◽

Vol 53 (1) ◽

pp. S328.6-S328

Author(s):

J. Zein ◽

E. Chbeir ◽

R. Albrecht ◽

C. Castle ◽

F. B. Taylor ◽

...

Keyword(s):

Disseminated Intravascular Coagulation ◽

Trauma Patients ◽

Intravascular Coagulation

Download Full-text

Validation of the COAST score for predicting acute traumatic coagulopathy: A retrospective single-centre cohort study

Trauma ◽

10.1177/1460408619838187 ◽

2019 ◽

Vol 22 (2) ◽

pp. 112-117

Author(s):

Sophie Thorn ◽

Martin Tonglet ◽

Marc Maegele ◽

Russell Gruen ◽

Biswadev Mitra

Keyword(s):

Cohort Study ◽

Early Identification ◽

Adverse Outcomes ◽

Trauma Patients ◽

Operating Characteristics ◽

Hospital Data ◽

Single Centre ◽

Acute Traumatic Coagulopathy ◽

Simple Method ◽

Traumatic Coagulopathy

Purpose Early identification of trauma patients at risk of developing acute traumatic coagulopathy is important in initiating appropriate, coagulopathy-focused treatment. A clinical acute traumatic coagulopathy prediction tool is a quick, simple method to evaluate risk. The COAST score was developed in Australia and we hypothesised that it could predict coagulopathy and bleeding-related adverse outcomes in other advanced trauma systems. We validated COAST on a single-centre cohort of trauma patients from a trauma centre in Belgium. Methods The COAST score was modified to suit available data; we used entrapment, blood pressure, temperature, major chest injury and abdominal injury to calculate the score. Acute traumatic coagulopathy was defined as international normalised ratio >1.5 or activated partial thromboplastin time >60 s upon arrival of the patient to the hospital. Data were extracted from the local trauma registry on patients that presented between 1 January and 31 December 2015. Results In all, 133 patients met the inclusion criteria (>16 years old, available COAST and outcome data) for analysis. The COAST score had an area under the receiver operating characteristics curve of 0.941 (95% CI: 0.884–0.999) and at COAST ≥3, it had 80% sensitivity and 96% specificity. The score also identified patients with higher rates of mortality, blood transfusion and emergent surgery. Conclusion This retrospective cohort study demonstrated the utility of the COAST score in identifying trauma patients who are likely to have bleeding-related poor outcomes. The early identification of these patients will facilitate timely, appropriate treatment for acute traumatic coagulopathy and minimise the risk of over-treatment. It can also be used to select patients with acute traumatic coagulopathy for trials involving therapeutic agents targeted at acute traumatic coagulopathy.

Download Full-text

Significant Correlations between Tissue Factor and Thrombin Markers in Trauma and Septic Patients with Disseminated Intravascular Coagulation

Thrombosis and Haemostasis ◽

10.1055/s-0037-1615025 ◽

1998 ◽

Vol 79 (06) ◽

pp. 1111-1115 ◽

Cited By ~ 96

Author(s):

Satoshi Nanzaki ◽

Shigeyuki Sasaki ◽

Osamu Kemmotsu ◽

Satoshi Gando

Keyword(s):

Tissue Factor ◽

Disseminated Intravascular Coagulation ◽

Thrombin Generation ◽

Trauma Patients ◽

Elevated Plasma ◽

Antigen Concentration ◽

Intravascular Coagulation ◽

Factor Antigen ◽

D Dimer

SummaryTo determine the role of plasma tissue factor on disseminated intravascular coagulation (DIC) in trauma and septic patients, and also to investigate the relationships between tissue factor and various thrombin markers, we made a prospective cohort study. Forty trauma patients and 20 patients with sepsis were classified into subgroups according to the complication of DIC. Plasma tissue factor antigen concentration (tissue factor), prothrombin fragment F1+2 (PF1+2), thrombin antithrombin complex (TAT), fibrinopeptide A (FPA), and D-dimer were measured on the day of admission (day 0), and on days 1, 2, 3, and 4 after admission. The levels of plasma tissue factor in the DIC group were more elevated than those of the non-DIC group in both the trauma and the septic patients. In patients with sepsis, tissue factor levels on days 0 through 4 in the non-DIC group showed markedly higher values than those in the control patients (135 ± 8 pg/ml). Significant correlations between tissue factor and PF1+2, TAT, FPA, and D-dimer were observed in the DIC patients, however, no such correlations were found in the non-DIC patients. These results suggest that elevated plasma tissue factor in patients with trauma and sepsis gives rise to thrombin generation, followed by intravascular coagulation.

Download Full-text

Plasma ADAMTS13 Activity Associates with Injury Severity in Pediatric Trauma Patients

Blood ◽

10.1182/blood.v128.22.3777.3777 ◽

2016 ◽

Vol 128 (22) ◽

pp. 3777-3777

Author(s):

Jenny K. McDaniel ◽

Ilan I Maizlin ◽

Michelle C. Shroyer ◽

Morgan E. Banks ◽

Jean-Francois Pittet ◽

...

Keyword(s):

Injury Severity ◽

Pediatric Trauma ◽

Initial Presentation ◽

Trauma Patients ◽

Adamts13 Activity ◽

Acute Traumatic Coagulopathy ◽

Time Period ◽

Increased Risk ◽

Significant Difference ◽

Traumatic Coagulopathy

Abstract Background: Acute traumatic coagulopathy occurs in both pediatric and adult trauma patients and is associated with an increased risk of mortality. Trauma patients not only have increased risk for hemorrhagic complications, but also are at increased risk for thrombosis due to multiple factors including local tissue injury, inflammation, and immobility. The complex underlying pathophysiology of coagulation abnormalities associated with traumatic injury have yet to be fully elucidated. Additionally, there are significant differences in the hemostatic system of pediatric patients compared to adults. Objectives: The purpose of this study was to determine the levels of coagulation parameters including von Willebrand factor (VWF) antigen and ADAMTS13 activity in pediatric trauma patients and evaluate for possible association with injury severity and/or mortality. Methods: This study utilized plasma specimens collected from pediatric trauma patients that presented to our institution over a 2-year time period. The specimens were collected at initial presentation and 24 hours later. The injury severity was estimated using both the Glasgow Coma Scale (GCS) and Injury Severity Score (ISS). A cohort of control samples was obtained from pediatric patients for elective surgical procedures over the same time period. Plasma VWF antigen was determined by a sandwich ELISA; plasma ADAMTS13 activity was determined by FRETS-VWF73. The results were determined by nonparametric tests for the differences in median values. Results: A total of 106 trauma patient samples at initial time point, 78 trauma samples at 24 hour time point, and 54 control samples were obtained and utilized for study. There were statistically significant differences (p<0.05) in the plasma levels of VWF antigen, ADAMTS13 activity, and the ratio of ADAMTS13 activity to VWF antigen for the trauma patient samples at initial presentation when compared to controls (Table 1). At 24 hours, there were still statistically significant differences between ADAMTS13 activity and the ratio of ADAMTS13 activity to VWF antigen in trauma patients compared to controls, but there was no significant difference in VWF antigen between the two cohorts (Table 2). There was a significant difference between the decrease in ADAMTS13 activity and injury severity as estimated by ISS ³ 15 or GCS < 8 at both time points; however, ADAMTS13 activity was not statistically different in survivors vs. non-survivors. A higher VWF antigen level at initial presentation was the only factor found to be significantly different in non-survivors. Conclusions: This study demonstrates significant differences in plasma ADAMTS13 activity and VWF antigen in pediatric trauma patients compared to controls. In patients with more severe injuries as estimated by GCS and ISS, there was also a significant association with decreased levels of ADAMTS13 activity. These finding may underlie part of the prothrombotic propensity in microcirculation that occurs in patients post-trauma. Further investigation is warranted to better understand the mechanisms of acute traumatic coagulopathy and potential prognostic factors, and to determine the most effective interventions for acute traumatic coagulopathy in the pediatric population. Disclosures Zheng: Ablynx: Consultancy; Alexion: Research Funding.

Download Full-text

Clinical course and outcome of disseminated intravascular coagulation diagnosed by Japanese Association for Acute Medicine criteria

Thrombosis and Haemostasis ◽

10.1160/th08-05-0306 ◽

2008 ◽

Vol 100 (12) ◽

pp. 1099-1105 ◽

Cited By ~ 34

Author(s):

Satoshi Gando ◽

Daizoh Saitoh ◽

Hiroshi Ogura ◽

Toshihiko Mayumi ◽

Kazuhide Koseki ◽

...

Keyword(s):

Disseminated Intravascular Coagulation ◽

Clinical Course ◽

Trauma Patients ◽

Acute Medicine ◽

Japanese Association ◽

Intravascular Coagulation ◽

Coagulation Abnormalities ◽

Failure Assessment ◽

Jaam Criteria ◽

Prothrombin Time Ratio

SummaryThe Japanese Association for Acute Medicine (JAAM) disseminated intravascular coagulation (DIC) study group recently announced new diagnostic criteria for DIC. These criteria have been prospectively validated and demonstrated to progress to overt DIC as defined by the International Society on Thrombosis and Haemostasis (ISTH).Although an underlying condition is essential for the development of DIC, it has never been clarified if patients with different underlying disorders have a similar course. Among 329 patients with DIC diagnosed by the JAAM criteria, those with underlying sepsis (n=98) or trauma (n=95) were compared. The 28-day mortality rate was significantly higher in sepsis patients than trauma patients (34.7% vs. 10.5%, p<0.0001).Within three days of fulfilling the JAAM criteria, sepsis patients had a lower platelet count, higher prothrombin time ratio, higher systemic inflammatory response syndrome score, and higher Sequential Organ Failure Assessment score compared with trauma patients. On day 3, a significantly higher percentage of trauma patients than sepsis patients showed improvement of DIC (64.2% vs. 30.6%, p<0.001).These differences were mainly due to patients with lower JAAM DIC scores. More than 50% of the JAAM DIC patients with sepsis who died within 28 days could not be detected by ISTH DIC criteria during the initial three days. In contrast, most trauma patients who died within 28 days had DIC simultaneously diagnosed by JAAM and ISTH criteria, except for those with brain death. These findings suggest that coagulation abnormalities, organ dysfunction, and the outcome of JAAM DIC differ between patients with sepsis and trauma.

Download Full-text