Incidence of Venous Thromboembolism in Hospitalized Coronavirus Disease 2019 Patients: A Systematic Review and Meta-Analysis.
ABSTRACT: 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: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:Many aspects of care such as management of hypercoagulable state in COVID-19 patients, especially those admitted to intensive care units is challenging in the rapidly evolving pandemic of novel coronavirus disease 2019 (COVID-19). We seek to systematically review the available evidence regarding the anticoagulation approach to prevent venous thromboembolism (VTE) among COVID-19 patients admitted to intensive care units. Electronic databases were searched for studies reporting venous thromboembolic events in patients admitted to the intensive care unit receiving any type of anticoagulation (prophylactic or therapeutic). The pooled prevalence (and 95% confidence interval [CI]) of VTE among patients receiving anticoagulant were calculated using the random-effects model. Subgroup pooled analyses were performed with studies reported prophylactic anticoagulation alone and with studies reported mixed prophylactic and therapeutic anticoagulation. We included twelve studies (8 Europe; 2 UK; 1 each from the US and China) in our systematic review and meta-analysis. All studies utilized LMWH or unfractionated heparin as their pharmacologic thromboprophylaxis, either prophylactic doses or therapeutic doses. Seven studies reported on the proportion of patients with the previous history of VTE (range 0-10%). The pooled prevalence of VTE among ICU patients receiving prophylactic or therapeutic anticoagulation across all studies was 31% (95% CI 20-43%). Subgroup pooled analysis limited to studies reported prophylactic anticoagulation alone and mixed (therapeutic and prophylactic anticoagulation) reported pooled prevalences of VTE of 38% (95% CI 10-70%) and 27% (95% CI 17-40%) respectively. With a high prevalence of thromboprophylaxis failure among COVID-19 patients admitted to intensive care units, individualised rather than protocolised VTE thromboprophylaxis would appear prudent at interim.
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:Several Western guidelines recommend the routine use of pharmacologic thromboprophylaxis for cancer surgery patients to prevent venous thromboembolism (VTE). However, the necessity of routine pharmacologic perioperative thromboprophylaxis in Asian gastric cancer (GC) patients has not been clearly determined. To determine the necessity of routine perioperative pharmacologic thromboprophylaxis in Korean gastric cancer patients, the incidence of postoperative VTE was prospectively evaluated in gastric cancer patients receiving surgery. Among 610 GC patients who had received surgery, 375 patents underwent routine duplex Doppler ultrasonography (DUS) on days 5-12 following surgery to detect VTE and then VTE-related symptoms and signs were checked at 4 weeks after surgery (cohort A). The 235 patients that declined DUS were registered to cohort B and the occurrence of postoperative VTE was retrospectively analyzed. In cohort A, symptomatic or asymptomatic VTE until 4 weeks after surgery was detected in 9 patients [2.4%; 95% confidence interval (CI); 0.9-3.9]. Tumor stage was a significant factor related to VTE development [stage I, 1.4%; stage II/III, 2.4%; stage IV, 9.7% (P = 0.008)]. In multivariate analysis, patients with stage IV had a higher postoperative VTE development [odds ratio, 8.18 (95% CI, 1.54-43.42)] than those with stage I. In cohort B, a low incidence of postoperative VTE was reaffirmed; only one postoperative VTE case (0.4%) was observed. In conclusion, the incidence of postoperative VTE in Korean GC patients was only 2.4%. Risk-stratified applications of perioperative pharmacologic thromboprophylaxis are thought to be more appropriate than the routine pharmacologic thromboprophylaxis in Korean GC patients receiving surgery.
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 association of severe coronavirus disease 2019 (COVID-19) with an increased risk of venous thromboembolism (VTE) has resulted in specific guidelines for its prevention and management. The VTE risk appears highest in those with critical care admission. The need for postdischarge thromboprophylaxis remains controversial, which is reflected in conflicting expert guideline recommendations. Our local protocol provides thromboprophylaxis to COVID-19 patients during admission only. We report postdischarge VTE data from an ongoing quality improvement program incorporating root-cause analysis of hospital-associated VTE (HA-VTE). Following 1877 hospital discharges associated with COVID-19, 9 episodes of HA-VTE were diagnosed within 42 days, giving a postdischarge rate of 4.8 per 1000 discharges. Over 2019, following 18?159 discharges associated with a medical admission; there were 56 episodes of HA-VTE within 42 days (3.1 per 1000 discharges). The odds ratio for postdischarge HA-VTE associated with COVID-19 compared with 2019 was 1.6 (95% confidence interval, 0.77-3.1). COVID-19 hospitalization does not appear to increase the risk of postdischarge HA-VTE compared with hospitalization with other acute medical illness. Given that the risk-benefit ratio of postdischarge thromboprophylaxis remains uncertain, randomized controlled trials to evaluate the role of continuing thromboprophylaxis in COVID-19 patients following hospital discharge are required.
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:Pharmacologic thromboprophylaxis is routinely recommended for Western cancer patients undergoing major surgery for prevention of venous thromboembolism (VTE). However, it is uncertainwhetherroutine administration of pharmacologic thromboprophylaxis is necessary in all Asian surgical cancer patients. This prospective study was conducted to examine the incidence of and risk factors for postoperative VTE in Korean colorectal cancer (CRC) patients undergoing major abdominal surgery.This study comprised two cohorts, and none of patients received perioperative pharmacologic thromboprophylaxis. In cohort A (n=400), patients were routinely screened for VTE using lower-extremity Doppler ultrasonography (DUS) on postoperative days 5-14. In cohort B (n=148), routine DUS was not performed, and imaging was only performed when there were symptoms or signs that were suspicious for VTE. The primary endpoint was the VTE incidence at 4 weeks postoperatively in cohort A.The postoperative incidence of VTE was 3.0% (n=12) in cohort A. Among the 12 patients, eight had distal calf vein thromboses and one had symptomatic thrombosis. Age ? 70 years (odds ratio [OR], 5.61), ? 2 comorbidities (OR, 13.42), and white blood cell counts of > 10,000/?L (OR, 17.43) were independent risk factors for postoperative VTE (p < 0.05). In cohort B, there was one case of VTE (0.7%).The postoperative incidence of VTE, which included asymptomatic cases, was 3.0% in Korean CRC patients who did not receive pharmacologic thromboprophylaxis. Perioperative pharmacologic thromboprophylaxis should be administered to Asian CRC patients on a risk-stratified basis.
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: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.