Semin Thromb Hemost
DOI: 10.1055/s-0041-1735454
Review Article

Dynamic Hemostasis and Fibrinolysis Assays in Intensive Care COVID-19 Patients and Association with Thrombosis and Bleeding—A Systematic Review and a Cohort Study

Christine Lodberg Hvas
1  Department of Anesthesiology and Intensive Care, Aarhus University Hospital, Aarhus, Denmark
2  Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
,
Julie Brogaard Larsen
3  Thrombosis and Hemostasis Research Unit, Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark
,
Kasper Adelborg
2  Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
3  Thrombosis and Hemostasis Research Unit, Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark
4  Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark
,
Steffen Christensen
1  Department of Anesthesiology and Intensive Care, Aarhus University Hospital, Aarhus, Denmark
2  Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
,
Anne-Mette Hvas
2  Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
3  Thrombosis and Hemostasis Research Unit, Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark
› Author Affiliations
Funding This study was supported by Department of Anesthesiology and Intensive Care and Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark and Health Research Foundation of Central Denmark Region, grant number A3001.

Abstract

Patients admitted to the intensive care unit (ICU) with coronavirus disease 2019 (COVID-19), the infectious pathology caused by severe acute respiratory syndrome coronavirus 2, have a high risk of thrombosis, though the precise mechanisms behind this remain unclarified. A systematic literature search in PubMed and EMBASE identified 18 prospective studies applying dynamic coagulation assays in ICU COVID-19 patients. Overall, these studies revealed normal or slightly reduced primary hemostasis, prolonged clot initiation, but increased clot firmness. Thrombin generation assay parameters generally were equivalent to the control groups or within reference range. Fibrinolysis assays showed increased clot resistance. Only six studies related their findings to clinical outcome. We also prospectively included 51 COVID-19 patients admitted to the ICU. Blood samples were examined on day 1, 3–4, and 7–8 with platelet function tests, rotational thromboelastometry (ROTEM), in vivo and ex vivo thrombin generation, and clot lysis assay. Data on thrombosis, bleeding, and mortality were recorded during 30 days. Primary hemostasis was comparable to healthy controls, but COVID-19 patients had longer ROTEM-clotting times and higher maximum clot firmness than healthy controls. Ex vivo thrombin generation was similar to that of healthy controls while in vivo thrombin generation markers, thrombin–antithrombin (TAT) complex, and prothrombin fragment 1 + 2 (F1 + 2) were higher in ICU COVID-19 patients than in healthy controls. Impaired fibrinolysis was present at all time points. TAT complex and F1 + 2 levels were significantly higher in patients developing thrombosis (n = 16) than in those without. In conclusion, only few previous studies employed dynamic hemostasis assays in COVID-19 ICU-patients and failed to reveal a clear association with development of thrombosis. In ICU COVID-19 patients, we confirmed normal platelet aggregation, while in vivo thrombin generation was increased and fibrinolysis decreased. Thrombosis may be driven by increased thrombin formation in vivo.



Publication History

Publication Date:
29 October 2021 (online)

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