Venous Thromboembolism among Hospitalized Patients with COVID-19 Undergoing Thromboprophylaxis: A Systematic Review and Meta-Analysis.
ABSTRACT: 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:<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:Background: Emerging evidence shows that coronavirus disease 2019 (COVID-19) is commonly complicated by coagulopathy, and venous thromboembolism (VTE) is considered to be a potential cause of unexplained death. Information on the incidence of VTE in COVID-19 patients, however, remains unclear. Method: English-language databases (PubMed, Embase, Cochrane), Chinese-language databases (CNKI, VIP, WANFANG), and preprint platforms were searched to identify studies with data of VTE occurrence in hospitalized COVID-19 patients. Pooled incidence and relative risks (RRs) of VTE were estimated by a random-effects model. Variations were examined based on clinical manifestations of VTE (pulmonary embolism-PE and deep vein thrombosis-DVT), disease severity (severe patients and non-severe patients), and rate of pharmacologic thromboprophylaxis (?60 and <60%). Sensitivity analyses were conducted to strengthen the robustness of results. Meta-regression was performed to explore the risk factors associated with VTE in COVID-19 patients. Results: A total of 17 studies involving 1,913 hospitalized COVID-19 patients were included. The pooled incidence of VTE was 25% (95% CI, 19-31%; I 2, 95.7%), with a significant difference between the incidence of PE (19%; 95% CI, 13-25%; I 2, 93.2%) and DVT (7%; 95% CI, 4-10%; I 2, 88.3%; P interaction < 0.001). Higher incidence was observed in severe COVID-19 patients (35%; 95 CI%, 25-44%; I 2, 92.4%) than that in non-severe patients (6%; 95 CI%, 3-10%; I 2, 62.2%; P interaction < 0.001). The high rate of pharmacologic thromboprophylaxis in COVID-19 patients (?60%) was associated with a lower incidence of VTE compared with the low pharmacologic thromboprophylaxis rate (<60%) (19 vs. 40%; P interaction = 0.052). Severe patients had a 3.76-fold increased risk of VTE compared with non-severe patients (RR, 4.76; 95% CI, 2.66-8.50; I 2, 47.0%). Sensitivity analyses confirmed the robustness of the primacy results. Conclusions: This meta-analysis revealed that the estimated VTE incidence was 25% in hospitalized COVID-19 patients. Higher incidence of VTE was observed in COVID-19 patients with a severe condition or with a low rate of pharmacologic thromboprophylaxis. Assessment of VTE risk is strongly recommended in COVID-19 patients, and effective measures of thromboprophylaxis should be taken in a timely manner for patients with high risk of VTE.
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:<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.
Project description:BACKGROUND:The incidence of venous thromboembolic events (VTE) in patients with COVID-19 is generally high but varies markedly. However, the relationship between anticoagulation and mortality in patients with COVID-19 is still unclear. METHODS:We performed a systematic review and meta-analysis to determine the incidence of VTE and evaluate the role of anticoagulation in patients with COVID-19. Random effects models were used to determine overall pooled estimates and 95% confidence intervals (CIs). RESULTS:After a database search, 25 observational studies (20 on VTE incidence and 5 on the relationship between anticoagulation and mortality) were included. The pooled incidence rates of VTE, pulmonary embolism (PE), and deep vein thrombosis (DVT) in hospitalised COVID-19 patients were 21% (95% CI 15-27%), 15% (95% CI 10-20%), and 27% (95% CI 19-36%), respectively. A meta-analysis of five studies found that anticoagulation was not associated with an increased risk of mortality in hospitalised COVID-19 patients (RR = 0.86, 95% CI, 0.69-1.09, P = 0.218; I2 = 47.4%). CONCLUSIONS:In conclusion, the incidence of VTE among hospitalised COVID-19 patients was high. Clinical trials are urgently needed to evaluate the roles of prophylactic and therapeutic anticoagulation in 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: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: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:Thrombosis is a common complication in patients with cancer. Whether thromboprophylaxis could benefit patients with cancer is unclear. The aim of this systematic review was to determine the efficacy and safety of thromboprophylaxis in patients with cancer undergoing surgery or chemotherapy. Methods:We searched the Cochrane Library, EMBASE, MEDLINE, EBSCOhost, and Web of Science for studies published before May 2018 to investigate whether thromboprophylaxis measures were more effective than a placebo in patients with cancer. Results:In total, 33 trials with 11,942 patients with cancer were identified. In patients with cancer undergoing surgery, the administration of thromboprophylaxis was associated with decreasing trends in venous thromboembolism (VTE) [relative risk (RR) 0.51, 95% confidence interval (CI) 0.32-0.81] and DVT (RR 0.53, 95% CI 0.33-0.87). In patients with cancer undergoing chemotherapy, the administration of thromboprophylaxis reduced the incidences of VTE, DVT, and pulmonary embolism compared with no thromboprophylaxis (RR 0.54, 95% CI 0.40-0.73; RR 0.47, 95% CI 0.31-0.73; RR 0.51, 95% CI 0.32-0.81, respectively). The pooled results regarding major bleeding showed no significant difference between prophylaxis and no prophylaxis in either the surgical or the chemotherapy groups (RR 2.35, 95% CI 0.74-7.52, p?=?0.1482, I2?=?0%; RR 1.30, 95% CI 0.93-1.83, p?=?0.1274, I2?=?0%, respectively). Conclusion:Thromboprophylaxis did not increase major bleeding events or the incidence of thrombocytopenia. All-cause mortality was not significantly different between those who received thromboprophylaxis and those who did not. This meta-analysis provides evidence that thromboprophylaxis can reduce the number of VTE and DVT events, with no apparent increase in the incidence of major bleeding in patients with cancer.
Project description:Venous thromboembolism (VTE) is one of the most common preventable causes of in-hospital death in trauma patients surviving their injuries. We assessed the prevalence, incidence and risk factors for deep venous thrombosis (DVT) and pulmonary embolism (PE) in critically ill trauma patients, in the setting of a mature and early mechanical and pharmacological thromboprophylaxis protocol.This was a prospective observational study on a cohort of patients from a surgical intensive care unit of a university level 1 trauma centre. We enrolled consecutive primary trauma patients expected to be in intensive care for ?48 h. Thromboprophylaxis was protocol driven. DVT screening was performed by duplex ultrasound of upper and lower extremities within the first 48 h, between 5 and 7 days and then weekly until discharge. We recorded VTE risk factors at baseline and on each examination day. Independent risk factors were analysed using a multivariate logistic regression.In 153 patients with a mean Injury Severity Score of 23 ± 12, the prevalence of VTE was 30.7%, 95 CI [23.7-38.8] (29.4% DVT and 4.6% PE). The incidence was 18%, 95 CI [14-24] patients-week. The median time of apparition of DVT was 6 days [1; 4]. The global protocol compliance was 77.8% with a median time of introduction of the pharmacological prophylaxis of 1 day [1; 2]. We identified four independent risk factors for VTE: central venous catheter (OR 4.39, 95 CI [1.1-29]), medullar injury (OR 5.59, 95 CI [1.7-12.9]), initial systolic arterial pressure <80 mmHg (OR 3.64, 95 CI [1.3-10.8]), and pelvic fracture (OR 3.04, 95 CI [1.2-7.9]).Despite a rigorous, protocol-driven thromboprophylaxis, critically ill trauma patients showed a high incidence of VTE. Further research is needed to tailor pharmacological prophylaxis and balance the risks and benefits.