David J Roh1, Katherine Eiseman, Hannah Kirsch, Nina Yoh, Amelia Boehme, Sachin Agarwal, Soojin Park, E Sander Connolly, Jan Claassen, Gebhard Wagener. 1. From the Division of Critical Care and Hospitalist Neurology (D.J.R., H.K., A.B., S.A., S.P., J.C.), Department of Neurology, New York-Presbyterian Hospital and Vagelos College of Physicians and Surgeons, Columbia University; Department of Neurology (A.B.), Vagelos College of Physicians and Surgeons, Columbia University; Department of Neurological Surgery (N.Y., E.S.C.), New York-Presbyterian Hospital and Vagelos College of Physicians and Surgeons, Columbia University; and Department of Anesthesiology (K.E., G.W.), Columbia University Irving Medical Center/NewYork-Presbyterian Hospital, New York, New York.
Abstract
BACKGROUND: Critically ill coronavirus disease 2019 (COVID-19) patients have frequent thrombotic complications and laboratory evidence of hypercoagulability. The relationship of coagulation tests and thrombosis requires investigation to identify best diagnostic and treatment approaches. We assessed for hypercoagulable characteristics in critically ill COVID-19 patients using rotational thromboelastometry (ROTEM) and explored relationships of D-dimer and ROTEM measurements with thrombotic complications. METHODS: Critically ill adult COVID-19 patients receiving ROTEM testing between March and April 2020 were analyzed. Patients receiving therapeutic anticoagulation before ROTEM were excluded. Rotational thromboelastometry measurements from COVID-19 patients were compared with non-COVID-19 patients matched by age, sex, and body mass index. Intergroup differences in ROTEM measurements were assessed using t tests. Correlations of D-dimer levels to ROTEM measurements were assessed in COVID-19 patients who had available concurrent testing. Intergroup differences of D-dimer and ROTEM measurements were explored in COVID-19 patients with and without thrombosis. RESULTS: Of 30 COVID-19 patients receiving ROTEM, we identified hypercoagulability from elevated fibrinogen compared with non-COVID-19 patients (fibrinogen assay maximum clot firmness [MCF], 47 ± 13 mm vs. 20 ± 7 mm; mean intergroup difference, 27.4 mm; 95% confidence interval [CI], 22.1-32.7 mm; p < 0.0001). In our COVID-19 cohort, thrombotic complications were identified in 33%. In COVID-19 patients developing thrombotic complications, we identified higher D-dimer levels (17.5 ± 4.3 μg/mL vs. 8.0 ± 6.3 μg/mL; mean difference, 9.5 μg/mL; 95% CI, 13.9-5.1; p < 0.0001) but lower fibrinogen assay MCF (39.7 ± 10.8 mm vs. 50.1 ± 12.0 mm; mean difference, -11.2 mm; 95% CI, -2.1 to -20.2; p = 0.02) compared with patients without thrombosis. We identified negative correlations of D-dimer levels and ROTEM MCF in these patients (r = -0.61; p = 0.001). CONCLUSION: We identified elevated D-dimer levels and hypercoagulable blood clot characteristics from increased fibrinogen on ROTEM testing in critically ill COVID-19 patients. However, we identified lower, albeit still hypercoagulable, ROTEM measurements of fibrinogen in COVID-19 patients with thrombotic complications compared with those without. Further work is required to externally validate these findings and to investigate the mechanistic drivers for these relationships to identify best diagnostic and treatment approaches for these patients. LEVEL OF EVIDENCE: Epidemiologic, level IV.
BACKGROUND: Critically ill coronavirus disease 2019 (COVID-19) patients have frequent thrombotic complications and laboratory evidence of hypercoagulability. The relationship of coagulation tests and thrombosis requires investigation to identify best diagnostic and treatment approaches. We assessed for hypercoagulable characteristics in critically ill COVID-19patients using rotational thromboelastometry (ROTEM) and explored relationships of D-dimer and ROTEM measurements with thrombotic complications. METHODS: Critically ill adult COVID-19patients receiving ROTEM testing between March and April 2020 were analyzed. Patients receiving therapeutic anticoagulation before ROTEM were excluded. Rotational thromboelastometry measurements from COVID-19patients were compared with non-COVID-19patients matched by age, sex, and body mass index. Intergroup differences in ROTEM measurements were assessed using t tests. Correlations of D-dimer levels to ROTEM measurements were assessed in COVID-19patients who had available concurrent testing. Intergroup differences of D-dimer and ROTEM measurements were explored in COVID-19patients with and without thrombosis. RESULTS: Of 30 COVID-19patients receiving ROTEM, we identified hypercoagulability from elevated fibrinogen compared with non-COVID-19patients (fibrinogen assay maximum clot firmness [MCF], 47 ± 13 mm vs. 20 ± 7 mm; mean intergroup difference, 27.4 mm; 95% confidence interval [CI], 22.1-32.7 mm; p < 0.0001). In our COVID-19 cohort, thrombotic complications were identified in 33%. In COVID-19patients developing thrombotic complications, we identified higher D-dimer levels (17.5 ± 4.3 μg/mL vs. 8.0 ± 6.3 μg/mL; mean difference, 9.5 μg/mL; 95% CI, 13.9-5.1; p < 0.0001) but lower fibrinogen assay MCF (39.7 ± 10.8 mm vs. 50.1 ± 12.0 mm; mean difference, -11.2 mm; 95% CI, -2.1 to -20.2; p = 0.02) compared with patients without thrombosis. We identified negative correlations of D-dimer levels and ROTEM MCF in these patients (r = -0.61; p = 0.001). CONCLUSION: We identified elevated D-dimer levels and hypercoagulable blood clot characteristics from increased fibrinogen on ROTEM testing in critically ill COVID-19patients. However, we identified lower, albeit still hypercoagulable, ROTEM measurements of fibrinogen in COVID-19patients with thrombotic complications compared with those without. Further work is required to externally validate these findings and to investigate the mechanistic drivers for these relationships to identify best diagnostic and treatment approaches for these patients. LEVEL OF EVIDENCE: Epidemiologic, level IV.
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