Thromboembolic Risk Factors, Outcomes, and Thromboprophylaxis in COV-19 Infected Hospitalized Adults: A Prospective Study (CORE-19) Stephanie
1 Williams ,
Dimitrios
2 Giannis ,
Damian
2 Inlall ,
Alex C.
1,2 Spyropoulos
1Donald
and Barbara Zucker School of Medicine at Hofstra/Northwell 2Institute of Health Innovations and Outcomes Research, The Feinstein Institutes for Medical Research, Northwell Health
Background Like many viruses, the novel COVID-19 virus has been associated with an increased risk of venous thrombotic embolism and disseminated intravascular coagulation 1,2. The risk of VTE has been found to be highest in those who have had more severely symptomatic cases of COVID-19, requiring critical care admission 2. Earlier reports on COVID-19 found elevated D-dimers 59.6% of those with more severe cases of COVID-19 3. Additionally, some studies have found that COVID-19 patients are at an increased risk of developing disseminated intravascular coagulation (DIC) 3,4,5. Roberts, et. al found that 4.8 of 1000 COVID-19 discharges experienced hospital-associated venous thromboembolisms within 42 days after discharge 2. Such findings suggesting procoagulant states – including elevated D-dimers, fibrin degradation products, and prothrombin time – have been associated with worse patient outcomes 4. Specifically, DIC was found to be present in 15 out of 21 COVID-19 non-survivors in the study conducted by Tang et al 4. While the associated risk is evident, the recommendations of thromboprophylaxis in COVID-19 patients are not universal.
Hypothesis The goal is the gather more information about the post-discharge events of patients previously hospitalized with COVID-19. It is predicted that these patients are at an increased risk of having a thromboembolic event.
Table 1: Population characteristics and post-discharge outcomes Population characteristics (N = 4914) Age (Mean (SD)) Male (N%) Post-discharge outcomes N (%) Rehospitalization Venous thromboembolism DVT PE SVT Splanchnic vein thrombosis Other vein thrombosis Arterial thromboembolism Stroke or TIA MI Major adverse limb event Systemic embolism Major bleeding All-cause mortality
60.9 (17.5) 2661 (54.1%) 15.4% (759 patients) 1.23% (60 patients) 0.96% (47 patients) 0.25% (12 patients) 0.04% (2 patients) 0.08% (4 patients) 0.45% (22 patients) 0.59% (29 patients) 0.27% (13 patients) 0.12% (6 patients) 2.00% (98 patients) 4.81% (237 patients)
Key DVT = Deep vein thrombosis
MI = Myocardial Infarction
PE = pulmonary embolism
Methods
Conclusions
Results
SVT = superficial vein thrombosis
This study is a retrospective and prospective registry of patients with positive polymerase chain reaction (PCR) confirmed COVID-19 infection within the Northwell Health system. Relevant outcomes will be assessed for the duration of patient hospitalization up to 90 days post-hospital discharge. The patient population will consist of hospitalized adult individuals over the age of 18 years old. Data of interest will be assessed by EMR and HIE review, a filtered Radiology Informatics database, and REDCap entry with an established data collection form (that includes telephonic patient calls) through 90 days post-discharge. All study data will be aggregated and systematically stored in a unified repository (data Figure 7: Independent CRISPR knockout of CDK4 or CDK6 mart) developed by the Center for Research Informatics and Innovation. This database will use automatic ETL (extract-transform- load) processes to query and does not cause dropout in most breast cancer cell lines transfer data from radiology databases, EHRs and the HIE and REDCap sources. studied. Two sets of survival analyses will be conducted based on two different cut-off time points. The first cut-off time point is discharge, so that the first set of analyses include all the patients in the registry. The second cut-off time point is the 90th day after discharge, so that this set of analyses include only patients who were followed up to 90 days after discharge. When the end point is all-cause mortality, standard survival analyses such as Cox proportional hazard model will be conducted to explore the risk factors associated with mortality, either in-hospital mortality or mortality up to 90 days after discharge. When the end point is thromboembolic event other than all-cause mortality, competing risk survival analyses will be conducted, in which the competing risk is all- cause mortality.
Based on preliminary data, it appears as though prophylactic measures to protect against thromboembolic events in those discharged from the hospital following a COVID-19 infection may be beneficial. The total major thrombosis event is roughly two times higher than previous studies have found it to be for a medically ill patient population. Deep vein thrombosis appears to be the most frequent thromboembolic consequence, followed by pulmonary embolism. Arterial thromboembolisms appear to occur less frequently than venous thromboembolism in our group of patients. Rehospitalization is found in 15.3% of patients, suggesting that more intensive follow up care is required. A secondary finding of this study is that major bleeding events are threefold higher than previous studies have found it to be for a medically ill population . This may suggest that such prophylactic treatment must be better monitored to prevent negative outcomes, such as major bleeding events.
Future Direction Further statistical analysis is required to determine the significance of these findings. The data should be statistically compared to the outcomes of a control population of medically ill (critical care) patients in order to determine the associated risk with COVID-19 infection for the major events discussed. Additionally, the population can be further characterized to see who may benefit – or be harmed – most by prophylactic thromboembolic treatment. The cause of mortality in this population should also be better characterized to determine risk of mortality with each post-discharge event.
Resources 1 Subramaniam
S, Scharrer I. Procoagulant activity during viral infections. Front Biosci Landmark Ed. 2018 Jan
1;23:1060–81. 2 Roberts,
L., Whyte, M., Georgiou, L., et al. Post-discharge venous thromboembolism following hospital admission with COVID-19. Blood 3 Guan
W-J, Ni Z-Y, Hu Y, Liang W-H, Ou C-Q, He J-X, et al. Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med. 2020 Feb 28 4 Tang
N, Li D, Wang X, Sun Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost JTH. 2020 Feb 19 5 Wang
YD, Zhang SP, Wei QZ, Zhao MM, Mei H, Zhang ZL, et al. [COVID-19 complicated with DIC: 2 cases report and literatures review]. Zhonghua Xue Ye Xue Za Zhi Zhonghua Xueyexue Zazhi. 2020 Mar 5;41(0):E001.