Prevalence of Acute Traumatic Coagulopathy in Acutely Traumatized Dogs and Association with Clinical and Laboratory Parameters at Presentation

Author(s):  
Yaiza Herrero ◽  
Rahel Jud Schefer ◽  
Benjamin M. Muri ◽  
Nadja E. Sigrist

Abstract Objective The aim of this study was to determine the prevalence of acute traumatic coagulopathy (ATC) and identify associated clinical and laboratory parameters including rotational thromboelastometry. Study Design Dogs presenting within 6 hours after trauma were allocated to the ATC or non-ATC group based on thromboelastometry analysis (ex-tem S, in-tem S, fib-tem S). ATC was defined as ≥2 hypocoagulable parameters in 1 profile and ≥ 1 hypocoagulable parameter in an additional profile. Parameters used were ex-tem and in-tem clotting time (CT), clot formation time (CFT), maximum clot firmness (MCF), maximum lysis and fib-tem MCF. Clinical and laboratory parameters at presentation, animal trauma triage (ATT) score, transfusion requirement and outcome were compared. Logistic regression was used to identify independent factors associated with ATC. Results Eleven of 33 dogs presented with ATC and showed ex-tem CT and CFT prolongation and reduced MCF amplitude in all profiles (all p < 0.001). pH (p = 0.043) and potassium concentration (p = 0.022) were significantly lower and bleeding (p = 0.027) and plasma transfusions (p = 0.001) more common in dogs with ATC. Time after trauma (p = 0.040) and Animal Trauma Triage score (p = 0.038, including haematocrit as confounding factor) were associated with the presence of ATC. Conclusion Acute traumatic coagulopathy is more common in traumatized dogs than previously reported. Acute traumatic coagulopathy was associated with acidosis, Animal trauma triage score, time after trauma and higher transfusion needs. Coagulation abnormalities include ex-tem CT and CFT prolongations and decreased clot strength.

2019 ◽  
Vol 32 (04) ◽  
pp. 289-296 ◽  
Author(s):  
Benjamin M. Muri ◽  
Rahel Jud Schefer ◽  
Nadja E. Sigrist

Objective The aim of this study was to describe coagulation abnormalities and incidence of acute traumatic coagulopathy (ATC) in traumatized cats over the first 24 hours after admission. Study Design This was a prospective observational study at the university teaching hospital including 26 cats with acute (<5 hours) trauma. Blood was sampled for rotational thromboelastometry (ROTEM) parameters at presentation and 6 hours/24 hours thereafter. Rotational thromboelastometry tracings were defined as hypo- or hypercoagulable if ≥ 2 of the following parameters were above or below institutional reference intervals: clotting time, clot formation time (CFT), maximum clot firmness, maximum lysis or maximum clot elasticity. Hypocoagulability at presentation was defined as ATC. Injury severity scores, treatment and survival to hospital discharge were retrieved from patient records. Results The incidence of ATC was 15% and the most common ROTEM abnormalities in cats with ATC were clotting time and CFT prolongation in both extrinsic and intrinsic ROTEM profiles. After 24 hours, compared with presentation, significantly more cats were hypercoagulable (p = 0.047) and none of the cats showed hypocoagulopathy. Cats with ATC received significantly more blood transfusions (p = 0.008). Conclusion The incidence of ATC in cats is higher than previously reported. Clotting time and CFT prolongations seem to be more common than hyperfibrinolysis and 53% of the cats became hypercoagulable within 24 hours. While the clinical relevance of ATC in cats needs to be investigated, cats diagnosed with ATC required significantly more blood transfusions.


2017 ◽  
Vol 126 (1) ◽  
pp. 115-127 ◽  
Author(s):  
Ross A. Davenport ◽  
Maria Guerreiro ◽  
Daniel Frith ◽  
Claire Rourke ◽  
Sean Platton ◽  
...  

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.


Diagnostics ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 1995
Author(s):  
Georgios N. Katsaras ◽  
Rozeta Sokou ◽  
Andreas G. Tsantes ◽  
Aikaterini Konstantinidi ◽  
Dimitra Gialamprinou ◽  
...  

Background: Although respiratory distress syndrome (RDS) constitutes a postnatal risk factor for bleeding and thromboembolic events in neonates, few studies have addressed this issue. We aimed to evaluate the hemostatic profile of neonates with RDS using rotational thromboelastometry (ROTEM). Methods: An observational study was conducted from November 2018 to November 2020 in the NICU of General Hospital of Nikaia “Aghios Panteleimon”. Preterm and term neonates with RDS hospitalized in the NICU were included and EXTEM (tissue factor-triggered extrinsic pathway), INTEM (ellagic acid activated intrinsic pathway), and FIBTEM (with platelet inhibitor cytochalasin D) assays were performed at the onset of the disease. Results: A hypocoagulable profile was noted in neonates with RDS compared to controls, expressed as significant prolongation of EXTEM CT (clotting time) and CFT (clot formation time), lower EXTEM A10 (amplitude at 10 min), MCF (maximum clot firmness), and LI60 (lysis index). Furthermore, prolongation of INTEM CFT and FIBTEM CT, and decreased INTEM and FIBTEM A10 and MCF were found in neonates with RDS. Multivariable logistic regression analysis showed that RDS is an independent factor for the recorded alterations in ROTEM variables. Conclusions: RDS is associated with a hypocoagulable profile and greater hyperfibrinolytic potential compared to healthy neonates.


Author(s):  
Syarifah Syahirah Syed Abas ◽  
Noralisa Abdul Karim ◽  
Petrick Periyasamy ◽  
Nurasyikin Yusof ◽  
Shamsul Azhar Shah ◽  
...  

Dengue mortality remains high despite monitoring against warning signs (WS). The associations of WS at febrile phase (FP) and hemorrhage at defervescence with the levels and kinetics of ROTEM, platelet count, cortisol, and ferritin were analyzed. Patients with confirmed dengue serology and WS in two centers were screened (n = 275) and 62 eligible patients were recruited prospectively over 9 months. “Vomiting” was the commonest WS (62.9%), with shortened clotting time (CT) INTEM (p = 0.01). “Hematocrit increase” showed significant prolonged CT INTEM, EXTEM, and FIBTEM (p < 0.05). “Platelet decrease” showed reduced platelet function and reduced clot amplitude at 10 min (A10) and maximum clot firmness (MCF) in INTEM and EXTEM (p < 0.001). The kinetics were reduced in platelet count, CT EXTEM, and cortisol (p < 0.05) but increased in CT INTEM (p = 0.03). At FP, “vomiting”, “hematocrit increase”, and “platelet decrease” demonstrated impaired CT, clot strengths A10/MCF and platelet functions. Majority (60/62, 96.7%) had non-severe outcomes, consistent with increase in cortisol kinetics. In conclusion, “vomiting”, “hematocrit increase” and “platelet decrease” at FP correlated with ROTEM. No conclusion could be made further regarding ferritin and cortisol. Larger study is required to study “hematocrit increase” with ROTEM as a potential marker for hemorrhage.


Perfusion ◽  
2020 ◽  
pp. 026765912094843
Author(s):  
Kazuhiro Shirozu ◽  
Yuji Karashima ◽  
Ken Yamaura

Introduction: Supplementation of fresh frozen plasma immediately after cardiopulmonary bypass is an effective method to enhance clotting ability as coagulation factors are consumed in the extracorporeal circuit during cardiopulmonary bypass. On the other hand, the anticoagulation factors in fresh frozen plasma can also deter the clotting ability. This study investigated the effect of fresh frozen plasma administration on the comprehensive clotting ability following cardiopulmonary bypass. Methods: This prospective observational study included 22 patients scheduled for cardiac surgery. Clotting times and maximum clot firmness were evaluated using the types of rotational thromboelastometry, intrinsic rotational thromboelastometry, and heparinase thromboelastography preoperatively, immediately after cardiopulmonary bypass, and 1 hour after cardiopulmonary bypass. Activated clotting time, antithrombin activity, and heparin concentration were also measured at these time-points. Results: Antithrombin activity (62.9 ± 7.2% vs. 51.1 ± 7.4%, p < 0.0001) and activated clotting time (132.6 ± 9.6% vs. 120.0 ± 9.0%, p < 0.001) were significantly higher 1 hour after cardiopulmonary bypass compared to measurements taken immediately after cardiopulmonary bypass. Heparin concentration 1 hour after cardiopulmonary bypass was significantly decreased compared to that immediately after cardiopulmonary bypass. On the other hand, maximum clot firmness determined via intrinsic rotational thromboelastometry was significantly greater 1 hour after cardiopulmonary bypass (53.8 ± 4.8 mm) than that immediately after cardiopulmonary bypass (49.5 ± 4.8 mm). Clotting time determined via intrinsic rotational thromboelastometry and heparinase thromboelastography was also significantly shorter 1 hour after cardiopulmonary bypass than that immediately after cardiopulmonary bypass. Conclusion: Fresh frozen plasma administration increased antithrombin activity and caused activated clotting time prolongation, but then increased clotting ability. Thus, testing by rotational thromboelastometry after cardiopulmonary bypass could be valuable in the detection of comprehensive clotting ability.


Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1075-1075
Author(s):  
Michael Adam Meledeo ◽  
Armando C Rodriguez ◽  
Chet R Voelker ◽  
James A Bynum ◽  
Andrew P Cap

Abstract Introduction The acute traumatic coagulopathy (ATC) which develops within 30 min following severe trauma with tissue damage and shock is defined by an increased prothrombin time (PT) and international normalized ratio (INR). While reduced thrombin might be expected in conjunction with elevated PT, recent clinical studies reveal paradoxically elevated thrombin generation potential in patients with ATC. We therefore hypothesized that the quantity of thrombin and the timing of thrombin-fibrinogen interactions both have an impact on clot quality; the exuberant production of thrombin found in trauma results in improper clot formation. Methods In vitro studies were conducted in human blood products and simplified synthetic plasma (consisting of purified human coagulation factors in HEPES buffered saline). Turbidimetry was used to observe fibrin crosslinking, while thromboelastography (TEG) was used to quantify clot formation parameters. Quantitation of fibrin(ogen) degradation products (FDPs) was conducted with the STA-R Evolution coagulation analyzer and by ELISA. A fluorogenic substrate was used to observe thrombin generation. Results Increasing the amount of prothrombin or thrombin (0-1400nM) in prothrombin-immunodepleted citrated plasma resulted in reduced clot times. The same dose response was examined in a buffered mixture of fibrinogen (300 mg/dl), FXIII (31.25nM), Ca2+ (2mM), and FXa (170nM-only used with prothrombin samples). However, while increasing prothrombin increased clot strength in both FII-deficient plasma and in the synthetic plasma, direct addition of thrombin decreased clot strength and by 3-fold at 1000nM versus 100nM (Figure 1; *p<0.05; **p<0.01; ***p<0.001 between groups at given concentration); fibrin density was similarly reduced in turbidimetric assays. In TEG, the thrombin dose response did not affect whole blood or platelet-rich plasma, but in platelet-poor plasma the same clot strength inhibition trend was observed. Thrombin generation from the combination of prothrombin (0-1000 nM), FXa (170 nM), and Ca2+ (2 mm) was found to be saturated above an initial prothrombin concentration of 500nM. An examination of FDPs from plasmin-degraded fibrinogen ± thrombin ± FXIII showed that FDPs from both crosslinked and uncrosslinked fibrin had 4-fold higher amounts of fibrin monomer and D-dimer than those produced from plasmin digestion of pure fibrinogen. When FDPs from thrombin +fibrinogen ± FXIII were supplemented back into fresh fibrinogen (0-50% of the final mixture) and allowed to clot again, there was a concentration-dependent decrease in fibrin formation rate (control: 0.15 OD/min; 50% FDP: 0.07 OD/min; p<0.001) which was not observed in samples treated with non-thrombin exposed FDPs. The use of these FDPs allowed for simulations of trauma patient plasma to be constructed using concentrations of plasma proteins associated with both "normal" trauma and the hypocoagulable state which manifests in ATC. When combining relevant levels of thrombin, fibrinogen, FDPs, and antithrombin III as are found in trauma patients that trend toward either good or bad outcomes, differences in TEG tracings can be observed illustrating the validity of these in vitro systems (Figure 2). Conclusions The dose responses of prothrombin versus thrombin reveal the significance of the timing of these reactions on proper clot formation. The conversion of prothrombin to thrombin mediated through FXa and FVa results in strong clots under normal circumstances. These results were reflected in both turbidimetry and TEG, indicating that fibrin crosslinking is being hindered by the presence of excess thrombin even in the presence of the antithrombin III. Additionally, FDPs from crosslinked substrates reduce new clot-making efficiency. Excess thrombin and significant increases in FDPs (which can result from fibrinolytic feedback loops) both contribute to an in vitro phenotype that may represent an underlying factor in the development of ATC. Disclosures No relevant conflicts of interest to declare.


PLoS ONE ◽  
2022 ◽  
Vol 17 (1) ◽  
pp. e0262600
Author(s):  
Rodrigo B. Aires ◽  
Alexandre A. de S. M. Soares ◽  
Ana Paula M. Gomides ◽  
André M. Nicola ◽  
Andréa Teixeira-Carvalho ◽  
...  

In patients with severe forms of COVID-19, thromboelastometry has been reported to display a hypercoagulant pattern. However, an algorithm to differentiate severe COVID-19 patients from nonsevere patients and healthy controls based on thromboelastometry parameters has not been developed. Forty-one patients over 18 years of age with positive qRT-PCR for SARS-CoV-2 were classified according to the severity of the disease: nonsevere (NS, n = 20) or severe (S, n = 21). A healthy control (HC, n = 9) group was also examined. Blood samples from all participants were tested by extrinsic (EXTEM), intrinsic (INTEM), non-activated (NATEM) and functional assessment of fibrinogen (FIBTEM) assays of thromboelastometry. The thrombodynamic potential index (TPI) was also calculated. Severe COVID-19 patients exhibited a thromboelastometry profile with clear hypercoagulability, which was significantly different from the NS and HC groups. Nonsevere COVID-19 cases showed a trend to thrombotic pole. The NATEM test suggested that nonsevere and severe COVID-19 patients presented endogenous coagulation activation (reduced clotting time and clot formation time). TPI data were significantly different between the NS and S groups. The maximum clot firmness profile obtained by FIBTEM showed moderate/elevated accuracy to differentiate severe patients from NS and HC. A decision tree algorithm based on the FIBTEM-MCF profile was proposed to differentiate S from HC and NS. Thromboelastometric parameters are a useful tool to differentiate the coagulation profile of nonsevere and severe COVID-19 patients for therapeutic intervention purposes.


2015 ◽  
Vol 35 (02) ◽  
pp. 181-186 ◽  
Author(s):  
T. Schneider ◽  
T. Siegemund ◽  
R. Siegemund ◽  
S. Petros

SummaryPublished data on thrombin generation variables and their correlation with thrombo - elastometry in the healthy population are scarce. This study aimed at assessing thrombin generation in adults and its correlation to classical rotational thromboelastometry (ROTEM).Thrombin generation was measured in platelet-poor plasma from healthy volunteers using the calibrated automated thrombogram (CAT) with 1 and 5 pmol/l tissue factor final concentration. Lag time, thrombin peak, time to thrombin peak and endogenous thrombin potential (ETP) were analyzed. ROTEM was performed without activator (NATEM) and data for clotting time, alpha angle, clot formation time and maximum clot firmness were correlated with those of thrombin generation.Altogether 132 persons (72 men, 60 women; median age: 48.0 years) were included. There was a positive non-linear correlation for age versus lag time (p < 0.001) and time to peak (p = 0.001), and almost linear correlation for age versus thrombin peak (p = 0.024) and ETP (p = 0.001), although with a moderate regression slope. Regarding ROTEM, there was a positive correlation between age and maximum clot firmness and alpha angle (p = 0.001), but a negative correlation between age and clotting time (p = 0.039). Comparing both assays, thrombin peak and ETP measured with a final tissue factor concentration of 5 pmol/l correlated significantly with alpha angle and maximum clot firmness.The age-related changes in CAT and ROTEM variables among adults are not linear. There is a significant correlation, although with a moderate slope, between data from CAT measured with 5 pmol/l tissue factor and ROTEM.


PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0243604
Author(s):  
Thiago Domingos Corrêa ◽  
Ricardo Luiz Cordioli ◽  
João Carlos Campos Guerra ◽  
Bruno Caldin da Silva ◽  
Roseny dos Reis Rodrigues ◽  
...  

Background Coagulation abnormalities in COVID-19 patients have not been addressed in depth. Objective To perform a longitudinal evaluation of coagulation profile of patients admitted to the ICU with COVID-19. Methods Conventional coagulation tests, rotational thromboelastometry (ROTEM), platelet function, fibrinolysis, antithrombin, protein C and S were measured at days 0, 1, 3, 7 and 14. Based on median total maximum SOFA score, patients were divided in two groups: SOFA ≤ 10 and SOFA > 10. Results Thirty patients were studied. Some conventional coagulation tests, as aPTT, PT and INR remained unchanged during the study period, while alterations on others coagulation laboratory tests were detected. Fibrinogen levels were increased in both groups. ROTEM maximum clot firmness increased in both groups from Day 0 to Day 14. Moreover, ROTEM–FIBTEM maximum clot firmness was high in both groups, with a slight decrease from day 0 to day 14 in group SOFA ≤ 10 and a slight increase during the same period in group SOFA > 10. Fibrinolysis was low and decreased over time in all groups, with the most pronounced decrease observed in INTEM maximum lysis in group SOFA > 10. Also, D-dimer plasma levels were higher than normal reference range in both groups and free protein S plasma levels were low in both groups at baseline and increased over time, Finally, patients in group SOFA > 10 had lower plasminogen levels and Protein C ​​than patients with SOFA <10, which may represent less fibrinolysis activity during a state of hypercoagulability. Conclusion COVID-19 patients have a pronounced hypercoagulability state, characterized by impaired endogenous anticoagulation and decreased fibrinolysis. The magnitude of coagulation abnormalities seems to correlate with the severity of organ dysfunction. The hypercoagulability state of COVID-19 patients was not only detected by ROTEM but it much more complex, where changes were observed on the fibrinolytic and endogenous anticoagulation system.


2015 ◽  
Vol 68 (9-10) ◽  
pp. 301-307 ◽  
Author(s):  
Sladjana Novakovic-Anucin ◽  
Dusica Kosanovic ◽  
Sanja Gnip ◽  
Visnja Canak ◽  
Velibor Cabarkapa ◽  
...  

Introduction. During liver transplantation, continuous laboratory monitoring of complex changes of the hemostatic system is necessary. The aim of this study was to compare two methods of monitoring: standard coagulation tests and rotational thromboelastometry. Material and Methods. The study included 17 patients who had undergone orthotopic liver transplantation in the Clinical Centre of Vojvodina, Serbia in the period from June 2008 to October 2012. The coagulation parameters (platelet count, activated partial thromboplastin time, prothrombin time and fibrinogen level) were compared with the thromboelastometric parameters (coagulation time, clot formation time and maximal clot firmness). Results. The results showed a statistically significant correlation between the platelet count and maximum clot firmness of the intrinsically (r=0.51, p<0.001) and extrinsically activated thromboelastometric assays (r=0.64, p<0.001). The fibrinogen level and maximum clot firmness of the fibrinogen thromboelastometric test correlated significantly as well (r=0.44, p=0.002). No significant correlations were found among the activated partial thromboplastin time, prothrombin time, coagulation time and clot formation time. Conclusion. For an adequate perioperative monitoring of the dynamic intraoperative hemostatic changes and the optimal use of blood derivatives during liver transplantation, the combined application of standard coagulation tests and rotational thromboelastometry should be considered whenever possible. Science and Technological Development, Republic of Serbia


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