Abstract
In patients with severe forms of COVID-19, thromboelastometry has been reported to display a hypercoagulant pattern. However, an algorithm to differentiate severe COVID-19 patients from nonsevere patients and healthy controls based on thromboelastometry parameters has not been developed. Forty-one patients over 18 years of age with positive qRT-PCR for SARS-CoV-2 were classified according to the severity of the disease: nonsevere (NS, n = 20) or severe (S, n = 21). A healthy control (HC, n = 9) group was also examined. Blood samples from all participants were tested by extrinsic (EXTEM), intrinsic (INTEM), non-activated (NATEM) and functional assessment of fibrinogen (FIBTEM) assays of thromboelastometry. The thrombodynamic potential index (TPI) was also calculated. Severe COVID-19 patients exhibited a thromboelastometry profile with clear hypercoagulability, which was significantly different from the NS and HC groups. Nonsevere COVID-19 cases showed a trend to thrombotic pole. The NATEM test suggested that nonsevere and severe COVID-19 patients presented endogenous coagulation activation (reduced clotting time and clot formation time). TPI data were significantly different between the NS and S groups. The maximum clot firmness profile obtained by FIBTEM showed moderate/elevated accuracy to differentiate severe patients from NS and HC. A decision tree algorithm based on the FIBTEM-MCF profile was proposed to differentiate S from HC and NS. Thromboelastometric parameters are a useful tool to differentiate the coagulation profile of nonsevere and severe COVID-19 patients for therapeutic intervention purposes.
Highlights
Patients with coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) have shown an increased frequency of thromboembolic phenomena since the beginning of the pandemic, which represents a high morbidity-mortality burden [1,2,3]
Since heparin thromboprophylaxis was administered to 90% of severe patients included in the present investigation and they still presented a clear INTEM hypercoagulability profile, we hypothesize that heparin therapy in usual doses may not have been sufficient to control the thrombotic tendency in severe COVID-19 patients and that INTEM analysis may represent a relevant biomarker to predict and adjust thromboprophylaxis management in COVID-19 patients, even knowing that INTEM is not highly sensitive to LMWH [25,26,27]
As the nonsevere patients exhibited this thromboelastometric parameter (NATEM-clotting time (CT)) suggestive of incipient hypercoagulopathy, our results suggested that even patients not hospitalized with nonsevere forms of COVID-19 may present a risk of developing thromboembolic events, which is probably due to increased levels of circulating tissue factor (TF) expression
Summary
Patients with coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) have shown an increased frequency of thromboembolic phenomena since the beginning of the pandemic, which represents a high morbidity-mortality burden [1,2,3] The pathophysiology of these findings is not fully established, information available to date shows that the changes in the hemostasis system seem to be triggered by the high production of proinflammatory cytokines [1,2,3,4,5]. The standard tests for the evaluation of coagulopathies are activated partial thromboplastin time (APTT), prothrombin time and activity (PTA), d-dimer and platelet count [4, 7] These methods present several limitations because they only cover the initial phase of coagulation and do not evaluate the different components involved in the dynamics of clot formation. The thrombodynamic potential index (TPI) [10] constitutes an alternative parameter for monitoring the risk of thromboembolic events by representing the global coagulation process [8, 9, 13]
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