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Viscoelastometric Testing to Assess Hemostasis of COVID-19: A Systematic Review
Marion Bareille1, Michaël Hardy2, Jonathan Douxfils3,4
1Namur Thrombosis and Hemostasis Center (NTHC), CHU UCL Namur, Université Catholique de Louvain, 5530 Yvoir, Belgium.
Insights
Viscoelastic testing (VET) in COVID-19 patients shows hypercoagulability and impaired fibrinolysis. However, study heterogeneity and small sample sizes limit the ability of VET to predict thrombotic events.
Area of Science:
- Coagulation and Thrombosis
- Infectious Diseases
- Critical Care Medicine
Background:
- SARS-CoV-2 infection is linked to a high risk of thrombosis.
- Accurate laboratory assessment of hypercoagulability and impaired fibrinolysis in COVID-19 remains challenging.
- Viscoelastic testing (VET) is a potential tool for evaluating coagulation abnormalities.
Purpose of the Study:
- To systematically review the literature on the usefulness of VET in predicting thrombotic events in COVID-19 patients.
- To analyze the impact of anticoagulation and heparin neutralization methods on VET results.
- To compare maximal clot mechanical strength with Clauss fibrinogen and scrutinize hypofibrinolysis diagnosis.
Main Methods:
- Systematic literature search of PubMed and Scopus databases (until December 31, 2020).
- Extraction of VET methods, parameters, patient features, and outcomes from 44 studies involving 1063 patients.
- Analysis of data from various VET devices (ROTEM, TEG, Quantra, ClotPro) with noted heterogeneity in reagents and protocols.
Main Results:
- Common findings include increased clot mechanical strength (primarily due to fibrinogen) and impaired fibrinolysis, especially with added plasminogen activators.
- Significant heterogeneity in study design, VET devices, reagents (limited heparin neutralization), and definitions of hypercoagulability was observed.
- Only 4 out of 16 studies found an association between VET results and thrombotic events; VET patterns often normalized with increased anticoagulation. Small sample sizes limit definitive conclusions.
Conclusions:
- Viscoelastic testing reveals a prothrombotic phenotype in COVID-19, characterized by hypercoagulability and hypofibrinolysis.
- Heterogeneity in VET methodologies and small study sizes hinder the definitive establishment of VET's predictive value for thrombotic events in COVID-19.
- Further standardized research is needed to clarify the role of VET in managing thrombotic risk in SARS-CoV-2 infection.
Abstract:
Infection by SARS-CoV-2 is associated with a high risk of thrombosis. The laboratory documentation of hypercoagulability and impaired fibrinolysis remains a challenge. Our aim was to assess the potential usefulness of viscoelastometric testing (VET) to predict thrombotic events in COVID-19 patients according to the literature. We also (i) analyzed the impact of anticoagulation and the methods used to neutralize heparin, (ii) analyzed whether maximal clot mechanical strength brings more information than Clauss fibrinogen, and (iii) critically scrutinized the diagnosis of hypofibrinolysis. We performed a systematic search in PubMed and Scopus databases until 31st December 2020. VET methods and parameters, and patients' features and outcomes were extracted. VET was performed for 1063 patients (893 intensive care unit (ICU) and 170 non-ICU, 44 studies). There was extensive heterogeneity concerning study design, VET device used (ROTEM, TEG, Quantra and ClotPro) and reagents (with non-systematic use of heparin neutralization), timing of assay, and definition of hypercoagulable state. Notably, only 4 out of 25 studies using ROTEM reported data with heparinase (HEPTEM). The common findings were increased clot mechanical strength mainly due to excessive fibrinogen component and impaired to absent fibrinolysis, more conspicuous in the presence of an added plasminogen activator. Only 4 studies out of the 16 that addressed the point found an association of VETs with thrombotic events. So-called functional fibrinogen assessed by VETs showed a variable correlation with Clauss fibrinogen. Abnormal VET pattern, often evidenced despite standard prophylactic anticoagulation, tended to normalize after increased dosing. VET studies reported heterogeneity, and small sample sizes do not support an association between the poorly defined prothrombotic phenotype of COVID-19 and thrombotic events.
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