Rotational Thromboelastometry predicts care level in COVID-19

AbstractBackgroundHigh prevalence of thrombotic events in severely ill COVID-19 patients have been reported. Pulmonary embolism as well as microembolization of vital organs may in these individuals be direct causes of death. The identification of patients at high risk of developing thrombosis may lead to targeted, more effective prophylactic treatment.ObjectivesTo test whether Rotational Thromboelastometry (ROTEM) indicates hypercoagulopathy in COVID-19 patients, and whether patients with severe disease have a more pronounced hypercoagulopathy compared with less severely ill patients.MethodsThe study was designed as a prospective observational study where COVID-19 patients over 18 years admitted to hospital were eligible for inclusion. Patients were divided into two groups depending on care level: 1) regular wards or 2) wards with specialized ventilation support. ROTEM was taken after admission and the data were compared with ROTEM in healthy controls.ResultsThe ROTEM variables Maximum Clot Firmness (EXTEM-/FIBTEM-MCF) were higher in COVID-19 patients compared with healthy controls (p<0.001) and higher in severely ill patients compared with patients at regular wards (p<0.05). Coagulation Time (EXTEM-CT) was longer and Clot Formation Time (EXTEM-CFT) shorter in COVID-19 patients compared with healthy controls. Our results suggest that hypercoagulopathy is present in hospitalized patients with mild to severe COVID-19 pneumonia.ConclusionROTEM variables were significantly different in COVID-19 patients early after admission compared with healthy controls. This pattern was more pronounced in patients with increased disease severity, suggesting that ROTEM-analysis may be useful to predict thromboembolic complications in these patients.

Download Full-text

Rotational Thromboelastometry Predicts Care Level in COVID-19: A Prospective, Observational Study.

10.21203/rs.3.rs-57906/v1 ◽

2020 ◽

Author(s):

Lou M. Almskog ◽

Agneta Wikman ◽

Jonas Svensson ◽

Michael Wanecek ◽

Matteo Bottai ◽

...

Keyword(s):

Observational Study ◽

Prospective Observational Study ◽

Severe Disease ◽

Healthy Controls ◽

Care Level ◽

Rotational Thromboelastometry ◽

High Prevalence ◽

Level 1 ◽

Clot Formation Time ◽

Maximum Clot Firmness

Abstract BackgroundHigh prevalence of thrombotic events in severely ill COVID-19 patients have been reported. Pulmonary embolism as well as microembolization of vital organs may in these individuals be direct causes of death. The identification of patients at high risk of developing thrombosis may lead to targeted, more effective prophylactic treatment. The aim of this study was to test whether Rotational Thromboelastometry (ROTEM) indicates hypercoagulopathy in COVID-19 patients, and whether patients with severe disease have a more pronounced hypercoagulopathy compared with less severely ill patients. MethodsThe study was designed as a prospective observational study where COVID-19 patients over 18 years admitted to hospital were eligible for inclusion. Patients were divided into two groups depending on care level: 1) regular wards or 2) wards with specialized ventilation support. ROTEM was taken after admission and the data were compared with ROTEM in healthy controls.ResultsThe ROTEM variables Maximum Clot Firmness (EXTEM-/FIBTEM-MCF) were higher in COVID-19 patients compared with healthy controls (p<0.001) and higher in severely ill patients compared with patients at regular wards (p<0.05). Coagulation Time (EXTEM-CT) was longer and Clot Formation Time (EXTEM-CFT) shorter in COVID-19 patients compared with healthy controls. Our results suggest that hypercoagulopathy is present in hospitalized patients with mild to severe COVID-19 pneumonia. ConclusionsROTEM variables were significantly different in COVID-19 patients early after admission compared with healthy controls. This pattern was more pronounced in patients with increased disease severity, suggesting that ROTEM-analysis may be useful to predict thromboembolic complications in these patients.

Download Full-text

Rotational thromboelastometry results are associated with care level in COVID-19

Journal of Thrombosis and Thrombolysis ◽

10.1007/s11239-020-02312-3 ◽

2020 ◽

Cited By ~ 1

Author(s):

Lou M. Almskog ◽

Agneta Wikman ◽

Jonas Svensson ◽

Michael Wanecek ◽

Matteo Bottai ◽

...

Keyword(s):

Disease Severity ◽

Blood Type ◽

Care Level ◽

Rotational Thromboelastometry ◽

Moderate Disease ◽

High Prevalence ◽

Coagulation Tests ◽

Ventilation Support ◽

Level 1 ◽

Maximum Clot Firmness

Abstract High prevalence of thrombotic events in severely ill COVID-19 patients have been reported. Pulmonary embolism as well as microembolization of vital organs may in these individuals be direct causes of death. The identification of patients at high risk of developing thrombosis may lead to targeted, more effective prophylactic treatment. The primary aim of this study was to test whether rotational thromboelastometry (ROTEM) at admission indicates hypercoagulopathy and predicts the disease severity, assessed as care level, in COVID-19 patients. The study was designed as a prospective, observational study where COVID-19 patients over 18 years admitted to hospital were eligible for inclusion. Patients were divided into two groups depending on care level: (1) regular wards or (2) wards with specialized ventilation support. Conventional coagulation tests, blood type and ROTEM were taken at admission. 60 patients were included; age 61 (median), 67% men, many with comorbidities (e.g. hypertension, diabetes). The ROTEM variables Maximum Clot Firmness (EXTEM-/FIBTEM-MCF) were higher in COVID-19 patients compared with in healthy controls (p < 0.001) and higher in severely ill patients compared with in patients at regular wards (p < 0.05). Our results suggest that hypercoagulopathy is present early in patients with mild to moderate disease, and more pronounced in severe COVID-19 pneumonia. Non-O blood types were not overrepresented in COVID-19 positive patients. ROTEM variables showed hypercoagulopathy at admission and this pattern was more pronounced in patients with increased disease severity. If this feature is to be used to predict the risk of thromboembolic complications further studies are warranted.

Download Full-text

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

Veterinary and Comparative Orthopaedics and Traumatology ◽

10.1055/s-0040-1721707 ◽

2021 ◽

Author(s):

Yaiza Herrero ◽

Rahel Jud Schefer ◽

Benjamin M. Muri ◽

Nadja E. Sigrist

Keyword(s):

Clotting Time ◽

Acute Traumatic Coagulopathy ◽

Rotational Thromboelastometry ◽

Clot Strength ◽

Laboratory Parameters ◽

Coagulation Abnormalities ◽

Trauma Triage ◽

Clot Formation Time ◽

Maximum Clot Firmness ◽

Traumatic Coagulopathy

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.

Download Full-text

Thromboelastometry in Neonates with Respiratory Distress Syndrome: A Pilot Study

Diagnostics ◽

10.3390/diagnostics11111995 ◽

2021 ◽

Vol 11 (11) ◽

pp. 1995

Author(s):

Georgios N. Katsaras ◽

Rozeta Sokou ◽

Andreas G. Tsantes ◽

Aikaterini Konstantinidi ◽

Dimitra Gialamprinou ◽

...

Keyword(s):

Respiratory Distress Syndrome ◽

Respiratory Distress ◽

Distress Syndrome ◽

Multivariable Logistic Regression Analysis ◽

Extrinsic Pathway ◽

Term Neonates ◽

Rotational Thromboelastometry ◽

Significant Prolongation ◽

Clot Formation Time ◽

Maximum Clot Firmness

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.

Download Full-text

Comparison of standard coagulation tests and rotational thromboelastometry for hemostatic system monitoring during orthotopic liver transplantation: Results from a pilot study

Medicinski pregled ◽

10.2298/mpns1510301n ◽

2015 ◽

Vol 68 (9-10) ◽

pp. 301-307 ◽

Cited By ~ 3

Author(s):

Sladjana Novakovic-Anucin ◽

Dusica Kosanovic ◽

Sanja Gnip ◽

Visnja Canak ◽

Velibor Cabarkapa ◽

...

Keyword(s):

Liver Transplantation ◽

Platelet Count ◽

Fibrinogen Level ◽

Activated Partial Thromboplastin Time ◽

Coagulation Time ◽

Rotational Thromboelastometry ◽

Hemostatic System ◽

Coagulation Tests ◽

Clot Formation Time ◽

Maximum Clot Firmness

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

Download Full-text

Hypercoagulation detected by Rotational Thromboelastometry predicts mortality in COVID-19: A risk model based on a prospective observational study.

TH Open ◽

10.1055/a-1725-9221 ◽

2021 ◽

Author(s):

Lou Mandelman Almskog ◽

Agneta Wikman ◽

Jonas Svensson ◽

Matteo Bottai ◽

Mariann Kotorman ◽

...

Keyword(s):

Observational Study ◽

Prediction Model ◽

Prospective Observational Study ◽

Risk Model ◽

Severe Disease ◽

Anticoagulation Therapy ◽

Respiratory Frequency ◽

Rotational Thromboelastometry ◽

Risk Of Death

ABSTRACT Background: Severe disease due to COVID-19 has been shown to be associated with hypercoagulation. The aim of this study was to assess Rotational Thromboelastometry (ROTEM®) as a marker of coagulopathy in hospitalized COVID-19 patients. Methods: This was a prospective, observational study where patients hospitalized due to a COVID-19 infection were eligible for inclusion. Conventional coagulation tests and ROTEM were taken after hospital admission, and patients were followed for 30 days. A prediction model including variables ROTEM EXTEM-MCF (Maximum Clot Firmness), which in previous data has been suggested a suitable marker of hypercoagulation, age and respiratory frequency was developed using logistic regression to evaluate the probability of death. Results: Out of the 141 patients included, 18 (13%) died within 30 days. In the final prediction model, the risk of death within 30 days for a patient hospitalized due to COVID-19 was increased with increased EXTEM-MCF, age and respiratory frequency. Longitudinal ROTEM data in the severely ill subpopulation showed enhanced hypercoagulation. In an in vitro analysis, no heparin effect on EXTEM-CT (Coagulation Time) was observed, supporting a SARS-CoV-2 effect on prolonged initiation of coagulation. Conclusions: Here we show that hypercoagulation measured with ROTEM predicts 30-days mortality in COVID-19. Longitudinal ROTEM data strengthen the hypothesis of hypercoagulation as a driver of severe disease in COVID-19. Thus, ROTEM may be a useful tool to assess disease severity in COVID-19 and could potentially guide anticoagulation therapy.

Download Full-text

Analysis of Racial Disparity in Plasma of Healthy Volunteers Using Rotational Thromboelastometry Reveals Higher Prothrombotic Profile in African Americans

Blood ◽

10.1182/blood.v124.21.5972.5972 ◽

2014 ◽

Vol 124 (21) ◽

pp. 5972-5972 ◽

Cited By ~ 1

Author(s):

Maissaa Janbain ◽

Walter J Liszewski ◽

Cindy A Leissinger

Keyword(s):

African Americans ◽

Healthy Volunteers ◽

Racial Differences ◽

Whole Blood ◽

Thrombin Generation ◽

Alpha Angle ◽

Formation Time ◽

Rotational Thromboelastometry ◽

Clot Formation Time ◽

Maximum Clot Firmness

Racial differences in the incidence of arterial and venous thrombotic events are well established in literature, with a higher incidence noted in African Americans compared to Caucasians. Several studies have tried to explain this difference, by looking separately at chemical biomarkers, socioeconomic and clinical risk factors. Yet the exact reason behind this disparity remains unclear. At least one study of thrombin generation suggested that African ethnicity was associated with increased peak thrombin generation when compared to Caucasians. Rotational thromboelastometry is a visco-elastic methodology that offers a global assessment of hemostasis using either whole blood or plasma. We explored the racial differences in rotational thromboelastometry findings using plasma samples from healthy volunteers. We studied a cohort of 9 otherwise healthy adult volunteers with no history of cardiovascular nor thromboembolic events, 5 African Americans and 4 Caucasians. After informed consent, we collected citrated whole blood samples and processed them within 3 hours of phlebotomy. Platelet free plasma, obtained after centrifugation of whole blood for 20 minutes, was kept frozen at -70°C, and then thawed at 37°C for 5 minutes prior to testing. Samples were re-calcified with star-tem® reagent, and then the in-tem® reagent was added. The latter contains an optimized concentration of ellagic acid and partial thromboplastin phospholipid from rabbit brain. Thromboelastometry parameters including Clot Formation Time, Alpha Angle, and Maximum Clot Firmness were determined. We then compared the data between the two study populations using parametric unpaired Student’s t-test. Our results showed that the Clot Formation Time was higher in the plasma of Caucasians when compared to African Americans with a difference between means of 40.1 ± 4.4 seconds (p <.0001); the Alpha Angle was lower in Caucasians with a difference between means of 3.45 ± 0.3 degrees (p <.0001); and the Maximum Clot Firmness was lower in Caucasians with a difference between means of 9.75 ± 2 mm (p <.01). These findings demonstrated that the plasma of Caucasians took longer to reach the maximum firmness, and this maximum firmness was less than that reached in the plasma of African Americans. This reveals a significantly increased prothrombotic profile in the plasma of African Americans compared to Caucasians. Despite the limited number of participants, the striking observed differences in the thromboelastometry parameters suggest that global assays may offer benefit in assessing thrombotic risks in disparate patient populations, as they incorporate multiple components of the hemostatic system. Higher numbers of subjects and assessment of both whole blood and plasma are indicated. We are currently in the process of expanding our cohort to confirm these preliminary results. Disclosures No relevant conflicts of interest to declare.

Download Full-text

Serum C-Reactive Protein and Interleukin-6 Levels as Biomarkers for Disease Severity and Clinical Outcomes in Patients with Idiopathic Granulomatous Mastitis

Journal of Clinical Medicine ◽

10.3390/jcm10102077 ◽

2021 ◽

Vol 10 (10) ◽

pp. 2077

Author(s):

Yi-Min Huang ◽

Chiao Lo ◽

Chiao-Feng Cheng ◽

Cheng-Hsun Lu ◽

Song-Chou Hsieh ◽

...

Keyword(s):

Disease Severity ◽

Severe Disease ◽

Linear Regression Analysis ◽

Multiple Linear Regression Analysis ◽

Serum Biomarkers ◽

Healthy Controls ◽

Granulomatous Mastitis ◽

C Reactive Protein ◽

Idiopathic Granulomatous Mastitis ◽

Reactive Protein

Idiopathic granulomatous mastitis (IGM) is a rare inflammatory breast disease mimicking breast cancer. Limited research has been conducted on the application of serum biomarkers. This study aims to investigate the association of serum biomarkers with disease severity in patients with IGM. From November 2011 to March 2020, medical records of patients with IGM were reviewed. Serum cytokine levels were measured in patients and healthy controls between July 2018 and March 2020. A total of 41 patients with histologically proven IGM were found. Serum interleukin (IL)-6 level was significantly higher in patients with IGM (n = 11) than healthy controls (n = 7). Serum IL-6 and C-reactive protein (CRP) levels were significantly higher in patients with severe disease than mild and moderate disease. Serum IL-6 (Spearman’s ρ = 0.855; p < 0.001) and CRP (Spearman’s ρ = 0.838; p = 0.001) levels were associated with time to resolution. A higher serum CRP level was associated with a longer time to resolution (B = 0.322; p < 0.001) in multiple linear regression analysis. Serum IL-6 and CRP levels can be used as biomarkers for the evaluation of disease severity in IGM. IL-6 may play a crucial role in the immunopathology of IGM.

Download Full-text

Pathological findings in rotation thromboelastometry associated with thromboembolic events in COVID-19 patients

Thrombosis Journal ◽

10.1186/s12959-021-00263-0 ◽

2021 ◽

Vol 19 (1) ◽

Cited By ~ 1

Author(s):

Kristina Boss ◽

Andreas Kribben ◽

Bartosz Tyczynski

Keyword(s):

Severe Sepsis ◽

Severe Disease ◽

Study Data ◽

Sepsis Group ◽

Similar Data ◽

Disease Course ◽

Thromboembolic Events ◽

Pathological Findings ◽

Fibrinolysis Shutdown ◽

Maximum Clot Firmness

Abstract Background Severe thromboembolic events are one of the major complications associated with COVID-19 infection, especially among critically ill patients. We analysed ROTEM measurements in COVID-19 patients with a severe disease course and in patients with severe sepsis. Methods In this study, data obtained by extended analysis of haemostasis with standard laboratory tests and thromboelastometry of 20 patients with severe course of COVID-19 were retrospectively analysed and compared with similar data from 20 patients with severe sepsis but no COVID-19. Results The thromboelastometry values obtained from 20 sepsis patients contained a maximum clot firmness above the normal range but among COVID-19 patients, hypercoagulability was much more pronounced, with significantly higher maximum clot firmness (FIBTEM: 38.4 ± 10.1 mm vs. 29.6 ± 10.8 mm; P = 0.012; EXTEM: 70.4 ± 10.4 mm vs. 60.6 ± 14.8 mm; P = 0.022). Additionally, fibrinogen levels were significantly higher among COVID-19 patients (757 ± 135 mg/dl vs. 498 ± 132 mg/dl, P < 0.0001). Furthermore, thromboelastometry showed fibrinolysis shutdown among COVID-19 patients with significantly lower maximum of lysis than among sepsis patients (EXTEM: 0.6 ± 1.2 % vs. 3.3 ± 3.7 %; P = 0.013). Seven of 20 COVID-19 patients experienced thromboembolic events, whereas no patient in the sepsis group experienced such events. Conclusions ROTEM analysis showed significantly different pathological findings characterized by hypercoagulability and fibrinolysis shutdown among COVID-19 patients with a severe disease course compared to patients with severe sepsis. These abnormalities seem to be associated with thromboembolic events.

Download Full-text

Coagulation under Mild Hypothermia Assessed by Thromboelastometry

Transfusion Medicine and Hemotherapy ◽

10.1159/000513922 ◽

2021 ◽

pp. 1-7

Author(s):

Tobias Nitschke ◽

Philipp Groene ◽

Alice-Christin Acevedo ◽

Tobias Kammerer ◽

Simon T. Schäfer

Keyword(s):

Mild Hypothermia ◽

Onset Time ◽

Rotational Thromboelastometry ◽

Lysis Time ◽

Sample Data ◽

In Vivo Testing ◽

Fibrinolytic Capacity ◽

Clot Formation Time

Introduction: While previous studies have shown a significant impact of extreme hypo- and hyperthermia on coagulation, effects of much more frequently occurring perioperative mild hypothermia are largely unknown. This study therefore aimed to analyze the effects of mild hypothermia using rotational thromboelastometry in vitro. Materials and Methods: Twelve healthy volunteers were included in this study. Standard thromboelastometric tests (EXTEM, INTEM, FIBTEM) were used to evaluate coagulation in vitro at 39, 37, 35.5, 35, and 33°C. Beyond standard thromboelastometric tests, we also evaluated the effects of mild hypothermia on the TPA-test (ClotPro, Enicor GmbH, Munich, Germany), a new test which aims to detect fibrinolytic capacity by adding tissue plasminogen activator to the sample. Data are presented as the median with 25/75th percentiles. Results: Extrinsically activated coagulation (measured by EXTEM) showed a significant increase in clot formation time (CFT; 37°C: 90 s [81/105] vs. 35°C: 109 s [99/126]; p = 0.0002), while maximum clot firmness (MCF) was not significantly reduced. Intrinsically activated coagulation (measured by INTEM) also showed a significant increase in CFT (37°C: 80 s [72/88] vs. 35°C: 94 s [86/109]; p = 0.0002) without significant effects on MCF. Mild hypothermia significantly increased both the lysis onset time (136 s [132/151; 37°C] vs. 162 s [141/228; 35°C], p = 0.0223) and lysis time (208 s [184/297; 37°C] vs. 249 s [215/358; 35°C]; p = 0.0259). Conclusion: This demonstrates that even under mild hypothermia coagulation is significantly altered in vitro. Perioperative temperature monitoring and management are greatly important and can help to prevent mild hypothermia and its adverse effects. Further investigation and in vivo testing of coagulation under mild hypothermia is needed.

Download Full-text