Venous thromboembolism in critically Ill patients with COVID-19: Results of a screening study for deep vein thrombosis.
ABSTRACT: Background:The rapid spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and coronavirus disease 2019 (COVID-19), has caused more than 3.9 million cases worldwide. Currently, there is great interest to assess venous thrombosis prevalence, diagnosis, prevention, and management in patients with COVID-19. Objectives:To determine the prevalence of venous thromboembolism (VTE) in critically ill patients with COVID-19, using lower limbs venous ultrasonography screening. Methods:Beginning March 8, we enrolled 25 patients who were admitted to the intensive care unit (ICU) with confirmed SARS-CoV-2 infections. The presence of lower extremity deep vein thrombosis (DVT) was systematically assessed by ultrasonography between day 5 and 10 after admission. The data reported here are those available up to May 9, 2020. Results:The mean (± standard deviation) age of the patients was 68 ± 11 years, and 64% were men. No patients had a history of VTE. During the ICU stay, 8 patients (32%) had a VTE; 6 (24%) a proximal DVT, and 5 (20%) a pulmonary embolism. The rate of symptomatic VTE was 24%, while 8% of patients had screen-detected DVT. Only those patients with a documented VTE received a therapeutic anticoagulant regimen. As of May 9, 2020, 5 patients had died (20%), 2 remained in the ICU (8%), and 18 were discharged (72%). Conclusions:In critically ill patients with SARS-CoV-2 infections, DVT screening at days 5-10 of admission yielded a 32% prevalence of VTE. Seventy-five percent of events occurred before screening. Earlier screening might be effective in optimizing care in ICU patients with COVID-19.
Project description:Despite thromboprophylaxis, patients with coronavirus disease 2019 (COVID-19) exhibit hypercoagulability and higher venous thromboembolic risk, although its real incidence is still unknown. The aim of this study was to evaluate the incidence of venous thromboembolism (VTE) in patients with COVID-19 admitted to both intensive care units (ICUs) and medical wards (MWs). Consecutive patients admitted for COVID-19 to the MW and the ICU at Padua University Hospital, all receiving thromboprophylaxis, underwent systematic ultrasonography of the internal jugular, and the upper and lower limbs veins every 7 days (± 1 day) after the admission; and, if negative, once-weekly until discharge or death. In case of suspected pulmonary embolism, a multidetector computed tomographic angiography was performed. The primary outcome was the proportion of any deep-vein thrombosis (DVT) and symptomatic pulmonary embolism in both groups. An extended blood coagulative test was performed as well. From March 4 to April 30, 2020, a total of 85 patients were investigated, 44 (52%) in MWs and 41 (48%) in the ICU. Despite thromboprophylaxis, VTE occurred in 12 patients in the MWs (27.3%) and 31 patients in the ICU (75.6%) with an odds ratio of 9.3 (95% confidence interval (CI) 3.5-24.5; P < 0.001). Multiple-site DVT occurred in 55.6% of patients (95% CI 39.6-70.5). Increased D-dimer levels significantly correlated with VTE (P = 0.001) and death (P = 0.015). Summarizing, patients with COVID-19 admitted to the MW or ICU showed a high frequency of venous thromboembolism, despite standard-dose or high-dose thromboprophylaxis. Whether thrombosis, particularly asymptomatic events, may play a role in the morbidity and mortality of patients with COVID-19 remain to be clarified.
Project description:The purpose of this study was to identify miRNAs that were dysregulated after the onset of COVID-19 and thus potentially be used for risk stratification (i.e., mortality). Therefore, we conducted a multi-center, retrospective longitudinal cohort study enrolling 142 patients with laboratory-confirmed SARS-CoV-2 infection who presented to two Canadian hospitals from May 2020 – December 2020 along with a cohort of 27 SARS-CoV-2 patients with mild upper respiratory tract symptoms and 69 SARS-CoV-2-negative patients from the ICU. Blood was biobanked from SARS-CoV-2 positive patients in the emergency department (mild), ward (moderate) or intensive care unit (severe). Assessment of miRNA expression and co-regulatory network generation revealed significant transcriptome dyregulation in pateints with severe COVID-19 that was largely different from SARS-CoV-2 negative patients in the ICU. Overall design: Platelet reduced plasma from either: (1) SARS-CoV-2 negative patients with mild upper respiratory tract symptoms, (2) patients with mild COVID-19, (3) patients with moderate COVID-19, (4) patients with severe COVID-19, and (5) SARS-CoV-2 negative patients from the ICU with upper respiratory tract illnesses was taken from a -80 freezer and thawed on ice. Sample Groups: (1) n=30 SARS-CoV-2 negative patients with mild upper respiratory tract symptoms (2) n=14 patients with mild COVID-19 (3) n=15 patients with moderate COVID-19 (4) n=45 patients with severe COVID-19 (5) n=31 SARS-CoV-2 negative patients from the ICU with upper respiratory tract symptoms. A total of 30uL of thawed plasma was co-incubated with 1:1 volumes of HTG Plasma Lysis buffer (pre-warmed to 50 degrees celsius) and 1/10th v/v proteinase K for three hours at 50 degrees celsius with shaking (200rpm).
Project description:<h4>Background</h4> COVID-19 appears to be associated with a high risk of venous thromboembolism (VTE). We aimed to systematically review and meta-analyze the risk of clinically relevant VTE in patients hospitalized for COVID-19. <h4>Methods</h4> This meta-analysis included original articles in English published from January 1st, 2020 to June 15th, 2020 in Pubmed/MEDLINE, Embase, Web of science, and Cochrane. Outcomes were major VTE, defined as any objectively diagnosed pulmonary embolism (PE) and/or proximal deep vein thrombosis (DVT). Primary analysis estimated the risk of VTE, stratified by acutely and critically ill inpatients. Secondary analyses explored the separate risk of proximal DVT and of PE; the risk of major VTE stratified by screening and by type of anticoagulation. <h4>Results</h4> In 33 studies (n?=?4009 inpatients) with heterogeneous thrombotic risk factors, VTE incidence was 9% (95%CI 5–13%, I2 =?92.5) overall, and 21% (95%CI 14–28%, I2 =?87.6%) for patients hospitalized in the ICU. Proximal lower limb DVT incidence was 3% (95%CI 1–5%, I2 =?87.0%) and 8% (95%CI 3–14%, I2 =?87.6%), respectively. PE incidence was 8% (95%CI 4–13%, I2 =?92.1%) and 17% (95%CI 11–25%, I2 =?89.3%), respectively. Screening and absence of anticoagulation were associated with a higher VTE incidence. When restricting to medically ill inpatients, the VTE incidence was 2% (95%CI 0–6%). <h4>Conclusions</h4> The risk of major VTE among COVID-19 inpatients is high but varies greatly with severity of the disease. These findings reinforce the need for the use of thromboprophylaxis in all COVID-19 inpatients and for clinical trials testing different thromboprophylaxis regimens in subgroups of COVID-19 inpatients. <h4>Trial registration</h4> The review protocol was registered in PROSPERO International Prospective Register of Systematic Reviews (CRD42020193369). <h4>Supplementary Information</h4> The online version contains supplementary material available at 10.1186/s12959-021-00266-x.
Project description:Coronavirus disease 2019 (COVID-19) is associated with coagulation activation and high incidence of venous thromboembolism (VTE) in severe patients despite routine thromboprophylaxis. Conflicting results exist regarding the epidemiology of VTE for unselected anticoagulated COVID-19 patients hospitalized in general wards. The aim of this study was to evaluate the prevalence of asymptomatic deep venous thrombosis (DVT) in unselected patients with COVID-19 recently hospitalized in general wards. We performed a systematic complete doppler ultrasound (CDU) at a median 4 days after admission in 42 consecutive COVID-19 patients hospitalized in general wards of our university hospital, irrespective of D-Dimer level, and retrospectively collected clinical, biological and outcome data from electronic charts. Thromboprophylaxis was systematically applied following a French national proposal. In our population, the prevalence of asymptomatic DVT was 19% (8/42 patients), with distal thrombosis in 7/8 cases and bilateral DVT in 4/8 cases. Symptomatic pulmonary embolism was detected in 4 (9.5%) patients, associated to DVT in one case. Compared to patients without DVT, patients with DVT were older and experienced poorer outcomes. In conclusion, prevalence of asymptomatic DVT is high in the first days of hospitalization of unselected COVID-19 patients in general wards and may be related to poor prognosis. Individualized assessment of thromboprophylaxis and early systematic screening for DVT is warranted in this context.
Project description:Background:Venous thromboembolism (VTE) is frequently observed in patients with coronavirus disease 2019 (COVID-19). However, reported VTE-rates differ substantially. Objectives:We aimed at evaluating available data and estimating the prevalence of VTE in COVID-19 patients. Methods:We conducted a systematic literature search (MEDLINE, EMBASE, WHO COVID-19 database) to identify studies reporting VTE-rates in COVID-19 patients. Studies with suspected high risk of bias were excluded from quantitative synthesis. Pooled outcome rates were obtained within a random effects meta-analysis. Subgroup analyses were performed for different settings (intensive care unit (ICU) vs. non-ICU hospitalization and screening vs. no screening) and the association of D-dimer levels and VTE-risk was explored. Results:Eighty-six studies (33,970 patients) were identified and 66 (28,173 patients, mean age: 62.6 years, 60% men, 20% ICU-patients) were included in quantitative analysis. The overall VTE-prevalence estimate was 14.1% (95%CI 11.6-16.9), 40.3% (95%CI 27.0-54.3) with ultrasound-screening and 9.5% (95%CI 7.5-11.7) without screening. Subgroup analysis revealed high heterogeneity, with a VTE-prevalence of 7.9% (95%CI 5.1-11.2) in non-ICU and 22.7% (95%CI 18.1-27.6) in ICU patients. Prevalence of pulmonary embolism (PE) in non-ICU and ICU patients was 3.5% (95%CI 2.2-5.1) and 13.7% (95%CI 10.0-17.9). Patients developing VTE had higher D-dimer levels (weighted mean difference 3.26 µg/ml (95%CI 2.76-3.77) than non-VTE patients. Conclusion:VTE occurs in 22.7% of patients with COVID-19 in the ICU, but VTE risk is also increased in non-ICU hospitalized patients. Patients developing VTE had higher D-dimer levels. Studies evaluating thromboprophylaxis strategies in patients with COVID-19 are needed to improve prevention of VTE.
Project description:BACKGROUND:Preliminary evidence indicates that prophylactic-dose thromboprophylaxis may be inadequate to control the increased risk of venous thromboembolism (VTE) in patients hospitalized for coronavirus disease 2019 (COVID-19) infection. Additionally, it remains unclear whether the D-dimer measurement is useful for VTE risk stratification among COVID-19 patients. This study aimed to offer benchmark data on the incidence of VTE and to examine the difference in D-dimer levels among anticoagulated COVID-19 patients with and without VTE incident. METHODS:A comprehensive literature review of PubMed from inception to May 2020 was performed for original studies that reported the frequency of VTE and death among COVID-19 patients who received thromboprophylaxis on hospitalization. The endpoints included VTE (a composite of pulmonary embolism (PE) or deep vein thrombosis (DVT)), PE, DVT, and mortality. RESULTS:A total of 11 cohort studies were included. Among hospitalized COVID-19 patients, 23.9% (95% confidence interval (CI), 16.2% to 33.7%; I2 = 93%) developed VTE despite anticoagulation. PE and DVT were detected in 11.6% (95% CI, 7.5% to 17.5%; I2 = 92%) and 11.9% (95% CI, 6.3% to 21.3%; I2 = 93%) of patients, respectively. Patients in the intensive care unit (ICU) had a higher risk for VTE (30.4% )95% CI, 19.6% to 43.9%)) than those in the ward (13.0% (95% CI, 5.9% to 26.3%)). The mortality was estimated at 21.3% (95% CI, 17.0% to 26.4%; I2 = 53%). COVID-19 patients who developed VTE had higher D-dimer levels than those who did not develop VTE (mean difference, 2.05 µg/mL; 95% CI, 0.30 to 3.80 µg/mL; P = 0.02). CONCLUSIONS:The heightened and heterogeneous risk of VTE in COVID-19 despite prophylactic anticoagulation calls into research on the pathogenesis of thromboembolic complications and strategy of thromboprophylaxis and risk stratification. Prominent elevation of D-dimer may be associated with VTE development and can be used to identify high-risk subsets.
Project description:BACKGROUND:Coronavirus disease 2019 (COVID-19) can lead to systemic coagulation activation and thrombotic complications. OBJECTIVES:To investigate the incidence of objectively confirmed venous thromboembolism (VTE) in hospitalized patients with COVID-19. METHODS:Single-center cohort study of 198 hospitalized patients with COVID-19. RESULTS:Seventy-five patients (38%) were admitted to the intensive care unit (ICU). At time of data collection, 16 (8%) were still hospitalized and 19% had died. During a median follow-up of 7 days (IQR, 3-13), 39 patients (20%) were diagnosed with VTE of whom 25 (13%) had symptomatic VTE, despite routine thrombosis prophylaxis. The cumulative incidences of VTE at 7, 14 and 21 days were 16% (95% CI, 10-22), 33% (95% CI, 23-43) and 42% (95% CI 30-54) respectively. For symptomatic VTE, these were 10% (95% CI, 5.8-16), 21% (95% CI, 14-30) and 25% (95% CI 16-36). VTE appeared to be associated with death (adjusted HR, 2.4; 95% CI, 1.02-5.5). The cumulative incidence of VTE was higher in the ICU (26% (95% CI, 17-37), 47% (95% CI, 34-58), and 59% (95% CI, 42-72) at 7, 14 and 21 days) than on the wards (any VTE and symptomatic VTE 5.8% (95% CI, 1.4-15), 9.2% (95% CI, 2.6-21), and 9.2% (2.6-21) at 7, 14, and 21 days). CONCLUSIONS:The observed risk for VTE in COVID-19 is high, particularly in ICU patients, which should lead to a high level of clinical suspicion and low threshold for diagnostic imaging for DVT or PE. Future research should focus on optimal diagnostic and prophylactic strategies to prevent VTE and potentially improve survival.
Project description:The coronavirus disease 2019 (COVID-19) pandemic due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has challenged health-care systems and physicians worldwide to attempt to provide the best care to their patients with an evolving understanding of this unique pathogen. This disease and its worldwide impact have sparked tremendous interest in the epidemiology, pathogenesis, and clinical consequences of COVID-19. This accumulating body of evidence has centered around case series and often empiric therapies as controlled trials are just getting underway. What is clear is that patients appear to be at higher risk for thrombotic disease states including acute coronary syndrome (ACS), venous thromboembolism (VTE) such as deep vein thrombosis (DVT) or pulmonary embolism (PE), or stroke. Patients with underlying cardiovascular disease are also at higher risk for morbidity and mortality if infected. These patients are commonly treated with anticoagulation and/or antiplatelet medications and less commonly thrombolysis during hospitalization, potentially with great benefit but the management of these medications can be difficult in potentially critically ill patients. In an effort to align practice patterns across a large health system (Jefferson Health 2,622 staffed inpatient beds and 319 intensive care unit (ICU) beds across 14 facilities), a task force was assembled to address the utilization of anti-thrombotic and anti-platelet therapy in COVID-19 positive or suspected patients. The task force incorporated experts in Cardiology, Vascular Medicine, Hematology, Vascular Surgery, Pharmacy, and Vascular Neurology. Current guidelines, consensus documents, and policy documents from specialty organizations were used to formulate health system recommendations. OBJECTIVE:Our goal is to provide guidance to the utilization of antithrombotic and antiplatelet therapies in patients with known or suspected COVID-19.
Project description:BACKGROUND:Venous thromboembolism (VTE) may complicate the course of Coronavirus Disease 2019 (COVID-19). OBJECTIVES:To evaluate the incidence of VTE in patients with COVID-19. METHODS:MEDLINE, EMBASE, and PubMed were searched up to 24th June 2020 for studies that evaluated the incidence of VTE, including pulmonary embolism (PE) and/or deep vein thrombosis (DVT), in patients with COVID-19. Pooled proportions with corresponding 95% confidence intervals (CI) and prediction intervals (PI) were calculated by random-effect meta-analysis. RESULTS:3487 patients from 30 studies were included. Based on very low-quality evidence due to heterogeneity and risk of bias, the incidence of VTE was 26% (95% PI, 6%-66%). PE with or without DVT occurred in 12% of patients (95% PI, 2%-46%) and DVT alone in 14% (95% PI, 1%-75%). Studies using standard algorithms for clinically suspected VTE reported PE in 13% of patients (95% PI, 2%-57%) and DVT in 6% (95% PI, 0%-60%), compared to 11% (95% PI, 2%-46%) and 24% (95% PI, 2%-85%) in studies using other diagnostic strategies or patient sampling. In patients admitted to intensive care units, VTE occurred in 24% (95% PI, 5%-66%), PE in 19% (95% PI, 6%-47%), and DVT alone in 7% (95% PI, 0%-69%). Corresponding values in general wards were respectively 9% (95% PI, 0%-94%), 4% (95% PI, 0%-100%), and 7% (95% CI, 1%-49%). CONCLUSIONS:VTE represents a frequent complication in hospitalized COVID-19 patients and often occurs as PE. The threshold for clinical suspicion should be low to trigger prompt diagnostic testing.
Project description:<h4>Background</h4> Hospitalized patients with COVID-19 and raised D-dimer levels have high rates of venous thromboembolism (VTE). <h4>Methods</h4> We used data from hospitalized patients with COVID-19 that were tested for pulmonary embolism (PE) or deep vein thrombosis (DVT) because of raised D-dimer levels. We aimed to identify patients at increased risk for VTE. <h4>Results</h4> From March 25 to July 5th, 2020, 1,306 hospitalized patients with COVID-19 and raised D-dimer levels underwent testing for VTE in 12 centers. In all, 171 of 714 (24%) had PE, and 161 of 810 (20%) had DVT. The median time elapsed from admission to VTE testing was 12 days, and the median time from D-dimer measurement to testing 2 days. Most patients with VTE were men (62%), mean age was 62 ?± ?15 years, 45% were in an intensive care unit. Overall, 681 patients (52%) received VTE prophylaxis with standard doses, 241 (18%) with intermediate doses and 100 (7.7%) with therapeutic doses of anticoagulants. On multivariable analysis, patients with D-dimer levels >20 times the upper normal range (19% of the whole cohort) were at increased risk for VTE (odds ratio [OR]: 3.24; 95%CI: 2.18–4.83), as were those with a platelet count <100,000/?L (OR: 4.17; 95%CI: 1.72–10.0). <h4>Conclusions</h4> Hospitalized patients with COVID-19 and D-dimer levels >20 times the upper normal range were at an increased risk for VTE. This may help to identify what patients could likely benefit from the use of higher than recommended doses of anticoagulants for VTE prophylaxis. Highlights • Hospitalized patients with COVID-19 and raised D-dimer levels have high rates of venous thromboembolism (VTE).• We used data from hospitalized patients with COVID-19 that were tested for venous thromboembolism (VTE) because of raised D-dimer levels, aimed to identify those at increased risk for VTE.• Patients with D-dimer levels >20 times the upper normal range (19% of the whole cohort) were at a 3-fold higher risk for VTE.• Our data support the identification of individuals with higher thrombotic risk.