Routine Venous Thromboembolism Prophylaxis May Be Inadequate in the Hypercoagulable State of Severe Coronavirus Disease 2019

Abstract

Objectives: The aim of this study was to determine the frequency of venous thromboembolism in critically ill coronavirus disease 2019 patients and associate a degree of inflammatory marker elevation to venous thromboembolism development.

Design: An observational study that identified patients with severe coronavirus disease 2019 between March 12, 2020, and March 31, 2020. Data reported are those available through May 6, 2020.

Setting: A multicenter study including three Indianapolis area academic hospitals.

Patients: Two-hundred forty consecutive patients with confirmed severe acute respiratory syndrome coronavirus 2 infection were admitted to one of three hospitals. One-hundred nine critically ill coronavirus disease 2019 patients admitted to the ICU were included in the analysis.

Interventions: All patients received routine subcutaneous chemical venous thromboembolism prophylaxis.

Measurements and main results: The primary outcome of this study was to determine the frequency of venous thromboembolism and the degree of inflammatory and coagulation marker elevation associated with venous thromboembolism development. Descriptive statistics outlined the frequency of venous thromboembolism at any time during severe coronavirus disease 2019. Clinical course and laboratory metrics were compared between patients that developed venous thromboembolism and patients that did not develop venous thromboembolism. Hypercoagulable thromboelastography was defined as two or more hypercoagulable parameters.

Main results: One-hundred nine patients developed severe coronavirus disease 2019 requiring ICU care. The mean (± SD) age was 61 ± 16 years and 57% were male. Seventy-five patients (69%) were discharged home, 7 patients (6%) remain in the hospital, and 27 patients (25%) died. Venous thromboembolism was diagnosed in 31 patients (28%) 8 ± 7 days after hospital admission, including two patients diagnosed with venous thromboembolism at presentation to the hospital. Elevated admission D-dimer and peak D-dimer were associated with venous thromboembolism development (p < 0.05). D-dimer greater than 2,600 ng/mL predicted venous thromboembolism with an area under the receiver operating characteristic curve of 0.760 (95% CI, 0.661-0.858; p < 0.0001), sensitivity of 89.7%, and specificity of 59.5%. Twelve patients (11%) had thromboelastography performed and 58% of these patients had a hypercoagulable study. The calculated coagulation index was hypercoagulable in 50% of patients with thromboelastography.

Conclusions: These data show that coronavirus disease 2019 results in a hypercoagulable state. Routine chemical venous thromboembolism prophylaxis may be inadequate in preventing venous thromboembolism in severe coronavirus disease 2019.

Figure 1.

Flow chart of study patients. COVID-19 = coronavirus disease 2019.

Figure 2.

Receiver operator characteristic (ROC) curve, area under the curve, sensitivity, and specificity of d-dimer and platelet count to detect venous thromboembolism.

Figure 3.

Thromboelastography in 12 patients with severe coronavirus disease 2019 (COVID-19). Values are reported as mean ± sd. CI = coagulation index, IU = Indiana University, K = kinetics, LY30 = fibrinolytic activity 30 minutes after maximum amplitude, MA = maximum amplitude, R = reaction time, TEG = thromboelastography, VTE = venous thromboembolism, α = alpha angle.