Thrombogenicity markers for early diagnosis and prognosis in COVID-19: a change from the current paradigm?

Paul A Gurbel, Kevin P Bliden, Jerrold H Levy, Naval Walia, Nicole Rapista, Alastair Cho, Christophe Jerjian, Udaya S Tantry, Paul A Gurbel, Kevin P Bliden, Jerrold H Levy, Naval Walia, Nicole Rapista, Alastair Cho, Christophe Jerjian, Udaya S Tantry

Abstract

Standard biomarkers have been widely used for COVID-19 diagnosis and prognosis. We hypothesize that thrombogenicity metrics measured by thromboelastography will provide better diagnostic and prognostic utility versus standard biomarkers in COVID-19 positive patients. In this observational prospective study, we included 119 hospitalized COVID-19 positive patients and 15 COVID-19 negative patients. On admission, we measured standard biomarkers and thrombogenicity using a novel thromboelastography assay (TEG-6s). In-hospital all-cause death and thrombotic occurrences (thromboembolism, myocardial infarction and stroke) were recorded. Most COVID-19 patients were African--Americans (68%). COVID-19 patients versus COVID-19 negative patients had higher platelet-fibrin clot strength (P-FCS), fibrin clot strength (FCS) and functional fibrinogen level (FLEV) (P ≤ 0.003 for all). The presence of high TEG-6 s metrics better discriminated COVID-19 positive from negative patients. COVID-19 positive patients with sequential organ failure assessment (SOFA) score at least 3 had higher P-FCS, FCS and FLEV than patients with scores less than 3 (P ≤ 0.001 for all comparisons). By multivariate analysis, the in-hospital composite endpoint occurrence of death and thrombotic events was independently associated with SOFA score more than 3 [odds ratio (OR) = 2.9, P = 0.03], diabetes (OR = 3.3, P = 0.02) and FCS > 40 mm (OR = 3.4, P = 0.02). This largest observational study suggested the early diagnostic and prognostic utility of thromboelastography to identify COVID-19 and should be considered hypothesis generating. Our results also support the recent FDA guidance regarding the importance of measurement of whole blood viscoelastic properties in COVID-19 patients. Our findings are consistent with the observation of higher hospitalization rates and poorer outcomes for African--Americans with COVID-19.

Trial registration: ClinicalTrials.gov NCT04493307.

Conflict of interest statement

Dr. Gurbel reports grants and personal fees from Bayer HealthCare LLC, Otitopic Inc, Amgen, Janssen, and US WorldMeds LLC; grants from Instrumentation Laboratory, Haemonetics, Medicure Inc, Idorsia Pharmaceuticals, and Hikari Dx; personal fees from UpToDate; Dr. Gurbel is a relator and expert witness in litigation involving clopidogrel; in addition, Dr. Gurbel has two patents, Detection of restenosis risk in patients issued and Assessment of cardiac health and thrombotic risk in a patient.

Dr. Levy serves on steering committees for Instrumentation Labs, Merck and Octapharma.

Dr. Tantry reports receiving honoraria from UptoDate and Aggredyne.

Other author reports no disclosures.

Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.

Figures

Fig. 1
Fig. 1
Thromboelastography and standard markers in COVID-19 positive and negative patients. FEU, fibrinogen equivalent units.

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Source: PubMed

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