SCCM Resource Library-63-D-Dimer and Fibrinogen Magnitude and Hypercoagulability by Thromboelastography in Severe COVID-19

Video Transcription

Hi, everyone. My name is Abhi Chandel, and I'm a second year Pulmonary Critical Care Fellow at Walter Reed National Military Medical Center in Bethesda, Maryland.  Thank you for joining me for this virtual presentation. I'll be discussing our group's research into the hypercoagulability in COVID-19.  Our research examined the association of D-dimer and fibrinogen with hypercoagulability and severe COVID-19 requiring extracorporeal membrane oxygenation.  We have no conflicts of interest to disclose. We would, however, like to take a moment to acknowledge the tireless, multidisciplinary  efforts in caring for patients involved in this study and caring for all patients with COVID-19 within the Inova healthcare system.  As an introduction, we note the D-dimer concentration has been used by institutions to identify  candidates for intensified anticoagulant treatment for venous thromboembolism prevention and for the mitigation of the microthrombotic complications associated with COVID-19.  Thromboelastography or TEG maximum amplitude has been validated as a marker of hypercoagulability. TEG maximum amplitude of greater than or equal to 68 millimeters has been utilized  as a marker of hypercoagulability in other conditions. The goal of the study was to evaluate the relationship between coagulation, inflammatory,  and TEG parameters in patients with COVID-19 on extracorporeal membrane oxygenation, otherwise known as ECMO.  We performed a single center retrospective analysis of consecutive patients that received ECMO for the treatment of COVID-19.  TEG, inflammatory, and coagulation markers were compared in patients with and without thrombotic complications.  Correlation tests were performed to identify the coagulation and inflammatory markers that best predict hypercoagulability as defined by an elevated TEG maximum amplitude.  Of note, we chose to perform this study in patients on ECMO as it is standard practice at our institution to obtain daily TEGs on these patients.  Thus, the study population increased the ease of implementation of this analysis. As a result, we collected 168 TEGs in 24 unique patients.  Patients were grouped by the presence or absence of diagnosed macrothrombosis during hospitalization. Graphs of the two groups are displayed here.  Patients with diagnosed macrothrombosis were significantly more likely to have higher median C-reactive protein and fibrinogen values.  D-dimer was found to be negatively correlated with maximum amplitude in patients with heparin, 5-valerudin, and an aggregate.  Alternatively, fibrinogen was positively correlated with maximum amplitude in all patients.  A receiver-operating curve was generated using fibrinogen to classify maximum amplitude greater than or equal to 68 mm.  A fibrinogen of greater than 441 mg per deciliter was 91.2% sensitive and 85.7% specific for identifying a maximum amplitude greater than or equal to 68 mm.  In conclusion, in our study of patients with severe COVID-19 on ECMO, we found that D-dimer  was negatively correlated with a surrogate marker of hypercoagulability, namely TEG maximum amplitude.  Given this result, we postulate that D-dimer concentration may reflect hemostatic perturbation  in patients on ECMO or the severity of COVID-19-related sepsis, rather than be directly reflective of hypercoagulability in this population.  The fibrinogen concentration of greater than 441 mg per deciliter was accurate for the identification of TEG maximum amplitude greater than 68 mm.  However, it should be noted that this study was small in size, and TEG maximum amplitude was not associated with macrothrombosis in this population.  Further study is necessary to determine if maximum amplitude and viscoelastic testing are accurate predictors of hypercoagulability in COVID-19.  Thank you very much for your interest in this presentation. Please feel free to contact myself or the study team with any questions regarding our work.

Video Summary

Abhi Chandel, a second-year Pulmonary Critical Care Fellow at Walter Reed National Military Medical Center, discusses their research on hypercoagulability in COVID-19. The study examined the association between D-dimer and fibrinogen levels and severe COVID-19 requiring extracorporeal membrane oxygenation (ECMO). They found that D-dimer was negatively correlated with a marker of hypercoagulability, while fibrinogen was positively correlated. A fibrinogen concentration greater than 441 mg per deciliter accurately identified hypercoagulability. However, the study was small, and further research is needed to determine the accuracy of coagulation markers in predicting hypercoagulability in COVID-19.

Asset Subtitle

Hematology, Crisis Management, 2021

Asset Caption

The Society of Critical Care Medicine's Critical Care Congress features internationally renowned faculty and content sessions highlighting the most up-to-date, evidence-based developments in critical care medicine. This is a presentation from the 2021 Critical Care Congress held virtually from January 31-February 12, 2021.

Abhimanyu Chandel, MD

Introduction/Hypothesis: Coronavirus disease 2019 (COVID-19) is associated with a high rate of thrombotic complications related to an acute inflammatory state. D-dimer has been established as a marker of disease severity in COVID-19. Despite a paucity of data, D-dimer concentration has been used by institutions to identify candidates for intensified anticoagulant treatment for prevention and mitigation of the thrombotic complications associated with COVID-19. Thromboelastography (TEG) maximum amplitude (MA) has been validated as a marker of hypercoagulability with previous research defining hypercoagulability by a TEG MA â‰¥ 68 mm. We examined the relationship between common clinical laboratory parameters and hypercoagulability as represented by TEG MA.

Methods: We performed a single center retrospective analysis of consecutive patients who received ECMO for the treatment of COVID-19 with simultaneous TEG, coagulation, and inflammatory markers (D-dimer, fibrinogen, ferritin, and C-reactive protein) drawn during hospitalization. TEG MA values and inflammatory markers were compared in patients with and without a thrombotic complication during admission. Correlation tests were performed to identify the coagulation and inflammatory markers that may predict hypercoagulability as defined by elevated TEG MA.

Results: 168 TEGs were available in 24 patients. C-reactive protein and fibrinogen were significantly higher in patients that developed a thrombotic event versus those that did not (p=0.038 and p=0.043 respectively). There was no difference in D-dimer between groups (p=0.312). D-dimer was negatively correlated with TEG MA (p<0.001) and explained little of the variance in this variable (adjusted R2=0.162). Fibrinogen was significantly positively correlated (p<0.001) with MA and explained over 50% of the variance. A fibrinogen > 441 mg/dL had high diagnostic accuracy (sensitivity of 91.2%, specificity of 85.7%) for the detection of MA â‰¥ 68 mm.

Conclusions: In critically ill patients with COVID-19, D-dimer had an inverse relationship with hypercoagulability as measured by TEG MA. D-dimer elevation may reflect severity of COVID-19 related sepsis rather than designate patients likely to benefit from anticoagulation. Fibrinogen concentration may represent a more useful marker of hypercoagulability in this population.

Meta Tag

Content Type Presentation

Knowledge Area Hematology

Knowledge Area Crisis Management

Knowledge Level Advanced

Membership Level Select

Tag COVID-19

Tag Coagulation

Year 2021

Keywords

hypercoagulability

COVID-19

D-dimer

fibrinogen levels

ECMO

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