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

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.

Serial Thromboelastography and the Development of Venous Thromboembolism in Critically Ill Patients With COVID-19

“…The differences between thromboelastography parameters in patients who developed VTE and those who did not narrowed over time, likely due to the exclusion of measurements in patients who developed VTE and/or died over time; yet, lower MA, α, G, and clotting index were more common in patients who subsequently developed VTE compared with those who did not at nearly every timepoint. Prior retrospective studies have shown an association between hypercoagulable thromboelastography and the development of VTE; the differences between our results and those studies may be attributed to differences in methodology including retrospective study design selecting for patients with concern for coagulopathy and contributing to ascertainment bias, use of thromboelastography without heparinase or the TEG®6 machine, and use of the combined endpoints of VTE or death instead of controlling for the competing risk of death (5, 25–27).…”

A guide to molecular and functional investigations of platelets to bridge basic and clinical sciences

“…Many other drugs targeting thrombosis are also being tested 19 . Techniques such as TEG, especially TEG6s, have proven useful in investigating the levels of thrombogenicity markers 139 and also evaluating the pharmacodynamic response to anticoagulants and aspirin in patients with COVID-19 (ref. 115 ).…”

COVID myocardial involvement presenting as left ventricular aneurysm and clot associated with normal coronary anatomy, deep vein thrombosis, and abnormal brachial artery flow-mediated dilatation

“…[ 1 2 3 4 ] The COVID infection has been reported to have raised fibrinogen levels and hypercoagulable state in a recent study. [ 5 ]…”