Project description:Hospitalized patients with coronavirus disease 2019 (COVID-19), particularly those admitted to the intensive care unit (ICU) are at high risk of morbidity and mortality. Several observational studies have described hemostatic derangements and thrombotic complications in patients with COVID-19. The aim of this review article is to summarize the current evidence on pathologic findings, pathophysiology, coagulation and hemostatic abnormalities, D-dimer's role in prognostication epidemiology and risk factors of thrombotic complications, and the role of prophylactic and therapeutic anticoagulation in patients with COVID-19. While existing evidence is limited in quality, COVID-19 appears to increase micro-and macro-vascular thrombosis rates in hospitalized and critically ill patients, which may contribute to the burden of disease. D-dimer can be used for risk stratification of hospitalized patients, but its role to guide anticoagulation therapy remains unclear. Evidence of higher quality is needed to address the role of therapeutic anticoagulation or high-intensity venous thromboembolism prophylaxis in COVID-19 patients. TAKE-HOME POINTS.
Project description:Introduction Venous and arterial thromboses are frequently observed complications in patients with severe novel coronavirus disease 2019 (COVID-19) infection who require hospital admission. In this study, we evaluate the epidemiology of venous and arterial thrombosis events in ambulatory and postdischarge patients with COVID-19 infection. Materials and Method EMBASE and MEDLINE were searched up to July 21, 2021, in addition to other sources. We included studies that assessed the epidemiology of venous and arterial thrombosis events in ambulatory and postdischarge COVID-19 patients. Results A total of 16 studies (102,779 patients) were identified. The overall proportion of venous thromboembolic events in all patients, that is, ambulatory and postdischarge, was 0.80% (95% confidence interval [CI]: 0.44-1.28), 0.28% (95% CI: 0.07-0.64), and 1.16% (95% CI: 0.69-1.74), respectively. Arterial events occurred in 0.75% (95% CI: 0.27-1.47) of all patients, 1.45% (95% CI: 1.10-1.86) of postdischarge patients, and 0.23% (95% CI: 0.019-0.66) of ambulatory patients. The pooled incidence rate estimates per 1,000 patient-days for VTE events were 0.06 (95% CI: 0.03-0.08) and 0.12 (95% CI: 0.07-0.19) for outpatients and postdischarge, respectively, whereas for arterial events were 0.10 (95% CI: 0-0.30) and 0.26 (95% CI: 0.16-0.37). Conclusion This study found a low risk of venous and arterial thrombi in ambulatory and postdischarge COVID-19 patients, with a higher risk in postdischarge patients compared with ambulatory patients. This suggests that regular universal thromboprophylaxis in these patient populations is probably not necessary.
Project description:Objectives: This study aimed to investigate the clinical features of arterial thrombosis and venous thromboembolism (VTE) in coronavirus disease 2019 (COVID-19). Methods: The CLOT-COVID Study was a retrospective, multicenter cohort study that enrolled 2,894 consecutively hospitalized patients with COVID-19 among 16 centers in Japan from April 2021 to September 2021. We compared the clinical features of arterial thrombosis and VTE. Results: Thrombosis was observed in 55 patients (1.9%) during hospitalization. Arterial thrombosis and VTE occurred in 12 (0.4%) and 36 (1.2%) patients, respectively. Among the 12 patients with arterial thrombosis, 9 (75%), 2 (17%), and 1 developed ischemic cerebral infarction, myocardial infarction, and acute limb ischemia, respectively, and there were five patients (42%) without comorbidities. Among 36 patients with VTE, 19 (53%) and 17 (47%) developed pulmonary embolism (PE) and deep vein thrombosis (DVT), respectively. PE was common in the early stages of hospitalization; whereas, DVT was common beyond the early stages of hospitalization. Conclusion: Among patients with COVID-19, arterial thrombosis was less common than VTE, although ischemic cerebral infarction seemed to be relatively common, and a certain number of patients developed arterial thrombosis even in the absence of known atherosclerosis risk factors.
Project description:COVID-19 is a global pandemic with a daily increasing number of affected individuals. Thrombosis is a severe complication of COVID-19 that leads to a worse clinical course with higher rates of mortality. Multiple lines of evidence suggest that hyperinflammation plays a crucial role in disease progression. This review compiles clinical data of COVID-19 patients who developed thrombotic complications to investigate the possible role of hyperinflammation in inducing hypercoagulation. A systematic literature search was performed using PubMed, Embase, Medline and Scopus to identify relevant clinical studies that investigated thrombotic manifestations and reported inflammatory and coagulation biomarkers in COVID-19 patients. Only 54 studies met our inclusion criteria, the majority of which demonstrated significantly elevated inflammatory markers. In the cohort studies with control, D-dimer was significantly higher in COVID-19 patients with thrombosis as compared to the control. Pulmonary embolism, deep vein thrombosis and strokes were frequently reported which could be attributed to the hyperinflammatory response associated with COVID-19 and/or to the direct viral activation of platelets and endothelial cells, two mechanisms that are discussed in this review. It is recommended that all admitted COVID-19 patients should be assessed for hypercoagulation. Furthermore, several studies have suggested that anticoagulation may be beneficial, especially in hospitalized non-ICU patients. Although vaccines against SARS-CoV-2 have been approved and distributed in several countries, research should continue in the field of prevention and treatment of COVID-19 and its severe complications including thrombosis due to the emergence of new variants against which the efficacy of the vaccines is not yet clear.
Project description:Deep venous thrombosis (DVT) is a severe complication of coronavirus disease 2019 (COVID-19). The purpose of this study was to study the prevalence, risk factors, anticoagulant therapy and sex differences of DVT in patients with COVID-19. The enrolled 121 hospitalized non-ventilator patients were confirmed positive for COVID-19. All suspected patients received color Doppler ultrasound (US) to screen for DVT in both lower extremities. Multivariate logistic regression was performed to identify risk factors related to DVT in COVID-19 patients. DVT was found in 48% of the asymptomatic COVID-19 patients with an increased PADUA or Caprini index using US scanning. The multivariate logistic regression determined that age (OR, 1.05; p = .0306), C-reactive protein (CRP) (OR, 1.02; p = .0040), and baseline D-dimer (OR, 1.42; p = .0010) were risk factors among COVID-19 patients. Although the most common DVT location was infrapopliteal (classes I and II), higher mortality in DVT-COVID-19 patients was confirmed. DVT-COVID-19 patients presented significant increases in CRP, neutrophil count, and D-dimer throughout the whole inpatient period compared to non-DVT-COVID-19 patients. Although anticoagulation therapy accelerated the recovery of lymphocytopenia in DVT patients, men DVT-COVID-19 patients with anticoagulant therapy showed significant higher CRP and neutrophil count vs. lymphocyte count (N/L) ratio, but showed lower lymphocyte counts compared to women DVT-COVID-19 patients. DVT is common in COVID-19 patients with high-risk factors, especially for older age and higher CRP and baseline D-dimer populations. It is important to consider sex differences in anticoagulant therapy among DVT-COVID-19 patients.
Project description:BackgroundAlthough the incidence of venous and arterial thrombosis after a COVID-19 diagnosis and hospitalization has been well described using data available from electronic health records (EHR), little is known about their incidence after mild infections.ObjectivesTo characterize the cumulative incidence and risk factors for thrombosis after a COVID-19 diagnosis among those identified through the EHR and those with a self-reported case.MethodsWe calculated the cumulative incidence of thromboembolism diagnoses after EHR-identified and self-reported cases in the North Carolina COVID-19 Community Partnership, a prospective, multisite, longitudinal surveillance cohort using a Kaplan-Meier approach. We performed Cox regression to estimate the hazard of a thromboembolism diagnosis after COVID-19 by comorbidities, vaccination status, and dominant SARS-CoV-2 variant.ResultsOf a cohort of comprising more than 39,500 participants from 6 North Carolina sites, there were 6271 self-reported or EHR-diagnosed cases of COVID-19 reported between July 1, 2020, and April 30, 2022, of which 46 participants were diagnosed with a new-onset thromboembolism in the 365 days after their reported case. Self-reported cases had a lower estimated cumulative incidence of 0.15% (95% CI, 0.03-0.28) by day 90 and 0.64% (95% CI, 0.30-0.97) by day 365 compared with EHR-based diagnoses that had cumulative incidences of 0.73% (95% CI, 0.36-1.09) and 1.78 (95% CI, 1.14-2.46) by days 90 and 365 (log-rank test P value <.001). Those hospitalized and with pre-existing pulmonary and cardiovascular diseases were associated with the highest risk of a thromboembolism.ConclusionWe observed a higher cumulative incidence of thromboembolism after EHR-identified COVID-19 than self-reported cases.
Project description:Background: Thrombosis is a characteristic complication in coronavirus disease 2019 (COVID-19). Since coagulopathy has been observed over the entire clinical course, thrombosis might be a clue to understanding the specific pathology in COVID-19. Currently, there is limited epidemiological data of COVID-19-associated thrombosis in the Japanese population and none regarding variant strains of SARS-CoV-2. Here, we elucidate the risk factors and the pattern of thrombosis in COVID-19 patients. Methods: The patients consecutively admitted to Tokyo Medical and Dental University Hospital with COVID-19 were retrospectively analyzed. SARS-CoV-2 variants of concern/interest (VOC/VOI) carrying the spike protein mutants E484K, N501Y, or L452R were identified by PCR-based analysis. All thrombotic events were diagnosed by clinical symptoms, ultrasonography, and/or radiological tests. Results: Among the 516 patients, 32 patients experienced 42 thromboembolic events. Advanced age, severe respiratory conditions, and several abnormal laboratory markers were associated with the development of thrombosis. While thrombotic events occurred in 13% of the patients with a severe respiratory condition, those events still occurred in 2.5% of the patients who did not require oxygen therapy. Elevated D-dimer and ferritin levels on admission were independent risk factors of thrombosis (adjusted odds ratio 9.39 and 3.11, 95% confidence interval 2.08-42.3, and 1.06-9.17, respectively). Of the thrombotic events, 22 were venous, whereas 20 were arterial. While patients with thrombosis received anticoagulation and antiinflammatory therapies with a higher proportion, the mortality rate, organ dysfunctions, and bleeding complications in these patients were higher than those without thrombosis. The incidence of thrombosis in COVID-19 became less frequent over time, such as during the replacement of the earlier strains of SARS-CoV-2 by VOC/VOI and during increased use of anticoagulatory therapeutics. Conclusion: This study elucidated that elevated D-dimer and ferritin levels are useful biomarkers of thrombosis in COVID-19 patients. The comparable incidence of arterial thrombosis with venous thrombosis and the development of thrombosis in less severe patients required further considerations for the management of Japanese patients with COVID-19. Further studies would be required to identify high-risk populations and establish appropriate interventions for thrombotic complications in COVID-19.
Project description:BackgroundThere are few data on the incidence of thrombosis among COVID-19 cases, with most research concentrated on hospitalised patients. We aimed to estimate the incidence of venous thromboembolism, arterial thromboembolism, and death among COVID-19 cases and to assess the impact of these events on the risks of hospitalisation and death.MethodsWe conducted a distributed network cohort study using primary care records from the Netherlands, Italy, Spain, and the UK, and outpatient specialist records from Germany. The Spanish database was linked to hospital admissions. Participants were followed up from the date of a diagnosis of COVID-19 or positive RT-PCR test for SARS-CoV-2 (index date) for 90 days. The primary study outcomes were venous thromboembolic events, arterial thromboembolic events, and death, all over the 90 days from the index date. We estimated cumulative incidences for the study outcomes. Multistate models were used to calculate adjusted hazard ratios (HRs) for the association between venous thromboembolism or arterial thromboembolism occurrence and risks of hospitalisation or COVID-19 fatality.FindingsOverall, 909 473 COVID-19 cases and 32 329 patients hospitalised with COVID-19 on or after Sept 1, 2020, were studied. The latest index dates across the databases ranged from Jan 30, 2021, to July 31, 2021. Cumulative 90-day incidence of venous thromboembolism ranged from 0·2% to 0·8% among COVID-19 cases, and up to 4·5% for those hospitalised. For arterial thromboembolism, estimates ranged from 0·1% to 0·8% among COVID-19 cases, increasing to 3·1% among those hospitalised. Case fatality ranged from 1·1% to 2·0% among patients with COVID-19, rising to 14·6% for hospitalised patients. The occurrence of venous thromboembolism in patients with COVID-19 was associated with an increased risk of death (adjusted HRs 4·42 [3·07-6·36] for those not hospitalised and 1·63 [1·39-1·90] for those hospitalised), as was the occurrence of arterial thromboembolism (3·16 [2·65-3·75] and 1·93 [1·57-2·37]).InterpretationRisks of venous thromboembolism and arterial thromboembolism were up to 1% among COVID-19 cases, and increased with age, among males, and in those who were hospitalised. Their occurrence was associated with excess mortality, underlying the importance of developing effective treatment strategies that reduce their frequency.FundingEuropean Medicines Agency.
Project description:AbstractDeep venous thrombosis (DVT) is associated with high mortality in coronavirus disease 2019 (COVID-19) but there remains uncertainty about the benefit of anti-coagulation prophylaxis and how to decide when ultrasound screening is indicated. We aimed to determine parameters predicting which COVID-19 patients are at risk of DVT and to assess the benefit of prophylactic anti-coagulation.Adult hospitalized patients with positive severe acute respiratory syndrome coronavirus-2 reverse transcription-polymerase chain reaction (RT-PCR) undergoing venous duplex ultrasound for DVT assessment (n = 451) were retrospectively reviewed. Clinical and laboratory data within 72 hours of ultrasound were collected. Using split sampling and a 10-fold cross-validation, a random forest model was developed to find the most important variables for predicting DVT. Different d-dimer cutoffs were examined for classification of DVT. We also compared the rate of DVT between the patients going and not going under thromboprophylaxis.DVT was found in 65 (14%) of 451 reverse transcription-polymerase chain reaction positive patients. The random forest model, trained and cross-validated on 2/3 of the original sample (n = 301), had area under the receiver operating characteristic curve = 0.91 (95% confidence interval [CI]: 0.85-0.97) for prediction of DVT in the test set (n = 150), with sensitivity = 93% (95%CI: 68%-99%) and specificity = 82% (95%CI: 75%-88%). The following variables had the highest importance: d-dimer, thromboprophylaxis, systolic blood pressure, admission to ultrasound interval, and platelets. Thromboprophylaxis reduced DVT risk 4-fold from 26% to 6% (P < .001), while anti-coagulation therapy led to hemorrhagic complications in 14 (22%) of 65 patients with DVT including 2 fatal intra-cranial hemorrhages. D-dimer was the most important predictor with area under curve = 0.79 (95%CI: 0.73-0.86) by itself, and a 5000 ng/mL threshold at 7 days postCOVID-19 symptom onset had 75% (95%CI: 53%-90%) sensitivity and 81% (95%CI: 72%-88%) specificity. In comparison with d-dimer alone, the random forest model showed 68% versus 32% specificity at 95% sensitivity, and 44% versus 23% sensitivity at 95% specificity.D-dimer >5000 ng/mL predicts DVT with high accuracy suggesting regular monitoring with d-dimer in the early stages of COVID-19 may be useful. A random forest model improved the prediction of DVT. Thromboprophylaxis reduced DVT in COVID-19 patients and should be considered in all patients. Full anti-coagulation therapy has a risk of life-threatening hemorrhage.