Venous Thromboembolism In COVID-19 Patients Research Articles

Characteristics, Outcomes, and Associations of Venous Thromboembolism in Diabetic Patients Infected With COVID-19 in Riyadh, Saudi Arabia.

Background The associations and risk factors for venous thromboembolism (VTE) among hospitalized COVID-19 patients remain ambiguous in the literature, with some conflicting findings, especially in Saudi Arabia. In this study, we aim to elaborate on these data by examining regional patient populations and exploring the incidence, lab findings, and outcomes of VTE among hospitalized COVID-19 patients known to have diabetes mellitus (DM). Methodology This cross-sectional study was conducted at King Abdulaziz Medical City in Riyadh. The BestCare system was used to collect patients' data between September 2020 and February 2022. JMP15 was used for data analysis. Frequencies and percentages were used for categorical data, and median and interquartile ranges were used for quantitative data. The chi-square and Kruskal-Wallis rank-sum tests were used to assess the difference between categorical and quantitative variables, respectively. Nominal logistical regression was used to assess diabetes as a risk factor for developing VTE among COVID-19 patients. Results Data from 153 admitted patients were collected after they satisfied the inclusion criteria. Of these patients, 39 (25.49%) developed VTE. The demographic data included age group, gender, and DM status presented as frequencies and percentages. Through bivariate analysis, patients with longer hospital stays had at least one episode of VTE (p = 0.0072). Using nominal logistic regression analysis, diabetes as a risk factor (odds ratio = 4.11, confidence interval = 0.955-5.05, p = 0.0287) was significantly associated with the development of VTE in COVID-19 patients. Conclusions Based on our study, diabetes proved significant when evaluating the possible factors regarding VTE development in COVID-19 patients. In addition, the length of stay also played a critical role in the severity of VTE in COVID-19 patients. Similar studies should be conducted on a national scale in Saudi Arabia to accomplish two goals: first, to gain further understanding of the impact of the variables investigated in our population, and second, to publish data that are more generalizable to the larger population of Saudi Arabia.

Clinical Characteristics of COVID-19 Coagulopathy, Experiences in a New York City Safety Net Hospital

Purpose/Objective: COVID-19 is a significant cause of morbidity and mortality in the inner-city population in New York City (NYC), with COVID-19 coagulopathy and venous thromboembolism (VTE) as major contributing factors. A recent meta-analysis of 17 studies demonstrated a pooled 25% increased risk of VTE incidence in hospitalized COVID-19 patients (Zhang et. al, 2020). To assess morbidity burden, the primary objective of this current study is to investigate COVID-19 coagulopathy incidence in hospitalized patients in an Afro-Caribbean NYC population. The secondary objective was to assess the clinical characteristics and risk factors of COVID-19 coagulopathy, classify disease severity and outcomes. Methods: A retrospective study was performed at the NYC Health and Hospitals/Kings County on patients hospitalized with COVID-19. Data was collected from March 1 st, 2020 to December 31 st, 2021 for hospitalized and intensive care patients. Information was collected on the incidence of VTE, type of VTE (deep vein thrombosis or pulmonary embolism), demographics, VTE prevention strategies, VTE management, inflammatory markers, and outcomes. GraphPad PRISM was used for statistical analysis, through unpaired t-tests and odds ratios, with p<0.05 indicating statistical significance. Results: The primary objective investigated 675 patients to assess COVID-19 incidence, with imaging-confirmed VTE incidence in 32 (4.74%), and mortality in 112 (16.6%) patients (Table 1). To assess factors that influence VTE, we assessed demographic, outcome and infection severity between 32 VTE patients, and 142 non-VTE patients (Table 2). Multivariable analysis of comorbidities demonstrated that obesity was an independent risk factor for VTE (OR=11.4938, 95% CI 4.3512 to 30.3615, p<0.001). Interestingly, prior VTE did not increase the risk of VTE between cohorts. Further, there is a trend towards increased mortality risk in VTE patients compared to non-VTE patients, although not statistically significant (OR= 2.7483, 95% CI 0.9332 to 8.0934, p=0.0666). We were unable to deduce differences between VTE prevention strategies between the cohorts due to insufficient power. Upon analyzing inflammatory markers, D-Dimers were determined to be significantly elevated in VTE patients compared to non-VTE patients (p=0.0274), whereas there was no significant difference between LDH or ferritin between the cohorts. Conclusions/Implications: This study characterized the incidence and demographics of COVID-19 coagulopathy in a safety net NYC hospital, wherein there is decreased VTE incidence compared to prior published literature (Zhang et. al, 2020). Our study also supports current literature which identifies obesity as a risk factor for VTE in COVID-19 patients (Wang et al, 2021). We hypothesize that BMI reduction may be protective against COVID-19 induced VTE risk, and targeted BMI reduction programs may mitigate COVID-19 severity. Future studies should continue to investigate COVID-19 risk reduction strategies in patients with comorbidities and can consider anticoagulation use based on risk factors.

Neutrophil-Lymphocyte Ratio and Platelet-Lymphocyte Ratio for an Early Detection of Venous Thromboembolism in COVID-19 Patients

Background: Venous Thromboembolism (VTE) is an umbrella term that includes both deep vein thrombosis (DVT) and pulmonary embolism (PE). COVID-19 infection has emerged as a risk factor for VTE; however, traditional methods of testing (D-dimer and Well's score) have been less than optimal. The neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte Ratio (PLR) have a role in diagnosing DVT in non-COVID19 patients. These two inexpensive values are readily available from the complete blood count (CBC). Objective: To determine the association of NLR and PLR on admission and imaging day with the incidence of VTE in COVID-19 patients. Methods: This was a historical cohort study of all patients admitted with COVID-19 from 2020-2021, who underwent duplex ultrasound (US) and/or computed tomography angiography (CTA) of the chest, and serial complete blood counts (CBC) with differential measurements during hospitalization. Patients who had risk factors for VTE (active malignancy, history of thrombophilia disorders and any anticoagulation therapy) were excluded. The NLR and PLR were calculated on admission and upon imaging for eligible patients. Data were analyzed using Student's t-test, analysis of variance, the x2 test and logistic regression. Results: We included 234 patients, 51.3% (120/234) female, 57.3% Black (134/234) with mean age 59.2 ± 15.9 years. The mean NLR on admission for all admitted patients was higher in the VTE group vs non-VTE group, 11.24 ±11.33 vs 7.66 ±5.16 respectively, (p=0.002). The mean NLR on admission for non-ICU patients was higher in the VTE group vs non-VTE group, 9.06 ± 5.72 vs 7.04 ± 4.53 respectively, (p=0.02). For ICU patients, the mean NLR on admission was higher in the VTE group vs non-VTE group, 14.49 ±16.01 vs 8.6±4.53 respectively, (p=0.02).. There was no association between PLR on admission, NLR and PLR on imaging and incidence of VTE. After controlling for sex, every unit increase in NLR at admission increased the risk of VTE by 6.8% (OR=1.068, p=0.005). Conclusion: NLR on admission may be a useful, readily available and inexpensive method of screening for VTE in patients with COVID-19 infection.

Predictive value of inflammatory and coagulation biomarkers for venous thromboembolism in COVID-19 patients.

The predictive value of coagulation markers for venous thromboembolism (VTE) in COVID-19 patients has been investigated with conflicting results. Our aim was to investigate the correlation between biomarkers and VTE and the predictive value of D-dimer for VTE in hospitalized COVID-19 patients. Complete blood count, inflammatory and coagulation biomarkers at admission were collected. VTE was defined as diagnosed pulmonary embolism or deep vein thrombosis. Events were defined as in-hospital death or ICU admission. Predictors of VTE were identified with Pearson prediction models. A ROC curve was constructed to assess the predictive value of D-dimer. 1651 participants were included, 111 VTE were identified. Events incidence was higher in the VTE group (49.5% vs 28.2%, p < 0.001). Neutrophil-lymphocyte ratio (NLR, 0.001; 95% CI 0.000-0.002; p 0.019) and D-dimer (0.00005; 95% CI 0.00002-0.00008; p < 0.001), Geneva score (0.026; 95% CI 0.012-0.040; p < 0.001) and Wells score (0.047; 95% CI 0.033-0.061; p < 0.001) were associated with VTE. D-dimer had a goor predictive value for VTE (ROC area 0.85, 95% CI 0.816-0.893), with an optimal cut-off value of 2677μg/L (Youden index of 0,602). Among coagulation biomarkers D-dimer had the best predictive value for VTE, but higher cut-off values should be used in COVID-19.

Lymphocytes, Mean Platelet Volume, and Albumin in Critically Ill COVID-19 Patients with Venous Thromboembolism.

As one of the frequent complications leading to poor prognosis in hospitalized COVID-19 patients, a better understanding of venous thromboembolism (VTE) in COVID-19 patients is needed. We conducted a single-center, retrospective study on 96 COVID-19 patients admitted to the intensive care unit (ICU) from April to June 2022, in Shanghai Renji Hospital. Records of these COVID-19 patients upon admission were reviewed for demographic information, co-morbidities, vaccinations, treatment, and laboratory tests. VTE occurred in 11 (11.5%) cases among 96 COVID-19 patients despite the standard thromboprophylaxis since ICU admission. In COVID-VTE patients, a significant increase in B cells and a decrease in Ts cells were observed and a strong negative correlation (r = -0.9524, P = .0003) was found between these two populations. In COVID-19 patients with VTE, increased MPV and decreased albumin levels were seen in addition to the common VTE indicators of D-dimer abnormalities. The altered lymphocyte composition in COVID-VTE patients is noteworthy. In addition to D-dimer, MPV and albumin levels might be novel indicators for the risk of VTE in COVID-19 patients.

Incidence and Prevalence of Myocarditis in COVID-19 Infections

The outbreak of COVID-19, caused by a novel virus, has led to a global pandemic with significant implications for public health. COVID-19 exhibits a wide range of manifestations, affecting multiple organs in addition to the respiratory system. Cardiovascular complications, including myocarditis, have been observed in a substantial proportion of hospitalized COVID-19 patients and are associated with adverse outcomes. Studies have reported varying rates of myocarditis incidence among COVID-19 patients, with seasonal variations and higher numbers observed in the summer. The relative numbers of myocarditis cases are highest in younger individuals, but the in-hospital case-fatality rate increases with age. COVID-19 patients with myocarditis are more likely to require intensive care and ventilation support. Myocarditis is independently associated with increased case-fatality and the occurrence of venous thromboembolism in COVID-19 patients. Understanding the incidence and prevalence of myocarditis in COVID-19 is essential for patient management and prognosis.

Abstract 15698: Logistic and Machine Learning Approaches to Identify Predictors of Venous Thromboembolism in Covid-19 Patients

Introduction: Venous thromboembolism (VTE) has a significantly higher incidence in COVID-19 patients when compared to other acute viral infections. The evidence on the risk factors of VTE in COVID-19 inhospital patients is still inconsistent. The information is of utmost importance, as a path to promote prevention, early diagnosis and treatment. Hypothesis: VTE predictors may be identified through logistic regression (LR) and machine learning (ML) approaches. Methods: This multicenter cohort study included consecutive COVID-19 adult patients from 16 hospitals, admitted between March and September, 2020. Deep venous thrombosis and pulmonary embolism were confirmed by objective imaging. LR analysis, tree-based boosting and bagging were used to investigate the association of variables upon hospital presentation with VTE. Results: Among 4,120 patients (median age 61 [interquartile range 48-72] years-old, 55.5% men, 39.3% admitted to intensive care unit), VTE was confirmed in 6.7%. In multivariate LR analysis, obesity (OR 1.50, 95%CI 1.11-2.02); being an ex-smoker (OR 1.44, 95%CI 1.03-2.01); surgery ≤ 90 days (OR 2.20, 95%CI 1.14-4.23); axillary temperature (OR 1.41, 95%CI 1.22-1.63); D-dimer ≥ 4 times above the upper limit of reference value (OR 2.16, 95%CI 1.26-3.67), lactate (OR 1.10, 95%CI 1.02-1.19), C-reactive protein levels (CRP, OR 1.09, 95% CI 1.01-1.18); and neutrophil count (OR 1.04, 95%CI 1.005-1.075) were independent predictors of VTE. Temperature at hospital presentation, SF ratio, neutrophil count, D-dimer, CRP and lactate levels were also identified as predictors by ML methods. Conclusions: By using ML and LR analysis, we showed that D-dimer, axillary temperature, neutrophil count, CPR and lactate levels are risk factors for VTE in COVID-19 patients. ML approaches were able to identify additional predictors. We suggest that patients presenting those risk factors at hospital admission should be more closely monitored for VTE development.

Role of Combined CT Pulmonary Angiography and Indirect CT Venography in Diagnosing Venous Thromboembolism in COVID-19 Patients - Experience From an Indian Quaternary Centre.

ObjectivesTo study the role of combined CTPA and indirect CT venogram to diagnose venous thromboembolism (VTE) in patients with COVID-19 pneumonia and to compare the clinical characteristics, laboratory parameters, CT findings and clinical outcomes between the VTE positive and negative groups.MethodsIn this retrospective study, 131 patients with COVID-19 pneumonia who underwent CTPA and venogram between August 2020 and January 2021 were included. Relevant demographical, clinical and laboratory data and CT images were collected. Two thoracic radiologists independently reviewed the CTPA and venogram images.ResultsVTE was identified in 29 patients (22% of the study population). CT venogram identified DVT in 9 patients. No statistical difference was observed between the two groups with respect to age, gender, BMI and presence of comorbidities. There was a significant difference in the hospital stay duration, which is increased in the VTE positive group. The number of patients who were dependent on oxygen and mortality were also high in the positive group. There was statistically significant difference in the mean D-dimer value and the mean Neutrophil/lymphocyte ratio, which were higher in the VTE positive group.ConclusionCombined CTPA and venogram can be used as a one-stop investigation for diagnosing PE and DVT of lower limbs in patients with COVID-19 pneumonia. CTPA with venogram should be performed in patients with D-dimer value in the range of 1000 – 1200 μg/L and above to rule out VTE as the hospital stay duration and final outcomes vary between the positive and negative groups.

Efficacy and Safety of Anticoagulants for COVID-19 Patients in the Intensive Care Unit: A Systematic Review and Meta-Analysis.

This study aims to analyze the efficacy and safety of anticoagulants for COVID-19 patients in the intensive care unit. A comprehensive search was conducted using databases such as MEDLINE, PubMed, EuropePMC, Science Direct, Google Scholar, Clinicaltrial.gov, The Cochrane Central Register of Controlled Trial (CENTRAL, Cochrane Library) and several other published articles from the systematic review up to March 31, 2021. The Newcastle-Ottawa Scale (NOS) was used for the studies' qualitative assessment. The primary outcome examined was mortality rate, while the secondary included the length of stay (LOS) in thei care unit; hospital length of stay (HOS), coagulation markers including D-dimer, Platelet count, aPTT, PT and fibrinogen; markers of inflammation specifically C-reactive protein; and other adverse events ranging from hemorrhage to thrombosis. Additionally, the quantitative synthesis was conducted using fixed and random effects model in "The Revman 5.4", while heterogeneity was tested using the I-squared (I2) measure. A total of 1,062 articles were found during the initial search step and eventually 12 were chosen to be analyzed quantitatively in a meta-analysis. Comparison of the results related to anticoagulant group with no anticoagulant or standard care treatment showed that anticoagulant group significantly reduced mortality rate with RR= 0.53; 95 % CI, 0.30-0.95; P= 0.03, with I2 = 88% and venous thromboembolism (VTE) RR = 0.53; 95% CI, 0.37-0.76; P = .0007 with I2 = 35%. Based on the results, anticoagulants can mitigate mortality rate and VTE in COVID-19 patients.

3D-PAST: Risk Assessment Model for Predicting Venous Thromboembolism in COVID-19.

Hypercoagulability is a recognized feature in SARS-CoV-2 infection. There exists a need for a dedicated risk assessment model (RAM) that can risk-stratify hospitalized COVID-19 patients for venous thromboembolism (VTE) and guide anticoagulation. We aimed to build a simple clinical model to predict VTE in COVID-19 patients. This large-cohort, retrospective study included adult patients admitted to four hospitals with PCR-confirmed SARS-CoV-2 infection. Model training was performed on 3531 patients hospitalized between March and December 2020 and validated on 2508 patients hospitalized between January and September 2021. Diagnosis of VTE was defined as acute deep vein thrombosis (DVT) or pulmonary embolism (PE). The novel RAM was based on commonly available parameters at hospital admission. LASSO regression and logistic regression were performed, risk scores were assigned to the significant variables, and cutoffs were derived. Seven variables with assigned scores were delineated as: DVT History = 2; High D-Dimer (>500–2000 ng/mL) = 2; Very High D-Dimer (>2000 ng/mL) = 5; PE History = 2; Low Albumin (<3.5 g/dL) = 1; Systolic Blood Pressure <120 mmHg = 1, Tachycardia (heart rate >100 bpm) = 1. The model had a sensitivity of 83% and specificity of 53%. This simple, robust clinical tool can help individualize thromboprophylaxis for COVID-19 patients based on their VTE risk category.

The Incidence of Venous Thromboembolism in Critically Ill Patients with SARS-CoV-2 Infection Compared with Critically Ill Influenza and Community-Acquired Pneumonia Patients: A Retrospective Chart Review.

The rate of venous thromboembolism in COVID-19 patients has been reported to be 30% (deep vein thrombosis 20% and pulmonary embolism 18%). This has been shown to be higher in COVID-19 patients admitted to the ICU. Prophylactic anticoagulation may be sufficient at ward level, but not in intensive care. A retrospective chart review was undertaken in a large university hospital. The review included 276 patients from COVID-19 Wave 1, COVID-19 Wave 2, influenza, and community-acquired pneumonia groups. The timeframe included patients admitted between 23 February 2014 and 12 May 2021. Clinical characteristics, outcomes, blood results, rates of venous thromboembolism, and anticoagulation status were recorded. The incidence of venous thromboembolism in COVID-19 Wave 1, COVID-19 Wave 2, influenza, and community-acquired pneumonia was 10.91%, 13.69%, 13.33%, and 6.81%, respectively (p = 0.481). The incidence of pulmonary embolism was 7.27%, 10.95%, 3.33%, and 5.68%, respectively (p = 0.350). The incidence of deep vein thrombosis was 5.45%, 5.48%, 10.00%, and 1.14%, respectively (p = 0.117). Although most patients were prophylactically anticoagulated, venous thromboembolism still occurred. Venous thromboembolism remains an important differential to consider in critically ill COVID-19 patients. The current literature does not advise therapeutic anticoagulation for thromboprophylaxis in the ICU.

Predictors of venous thromboembolism in COVID-19 patients: results of the COVID-19 Brazilian Registry.

Previous studies that assessed risk factors for venous thromboembolism (VTE) in COVID-19 patients have shown inconsistent results. Our aim was to investigate VTE predictors by both logistic regression (LR) and machine learning (ML) approaches, due to their potential complementarity. This cohort study of a large Brazilian COVID-19 Registry included 4120 COVID-19 adult patients from 16 hospitals. Symptomatic VTE was confirmed by objective imaging. LR analysis, tree-based boosting, and bagging were used to investigate the association of variables upon hospital presentation with VTE. Among 4,120 patients (55.5% men, 39.3% critical patients), VTE was confirmed in 6.7%. In multivariate LR analysis, obesity (OR 1.50, 95% CI 1.11–2.02); being an ex-smoker (OR 1.44, 95% CI 1.03–2.01); surgery ≤ 90 days (OR 2.20, 95% CI 1.14–4.23); axillary temperature (OR 1.41, 95% CI 1.22–1.63); D-dimer ≥ 4 times above the upper limit of reference value (OR 2.16, 95% CI 1.26–3.67), lactate (OR 1.10, 95% CI 1.02–1.19), C-reactive protein levels (CRP, OR 1.09, 95% CI 1.01–1.18); and neutrophil count (OR 1.04, 95% CI 1.005–1.075) were independent predictors of VTE. Atrial fibrillation, peripheral oxygen saturation/inspired oxygen fraction (SF) ratio and prophylactic use of anticoagulants were protective. Temperature at admission, SF ratio, neutrophil count, D-dimer, CRP and lactate levels were also identified as predictors by ML methods. By using ML and LR analyses, we showed that D-dimer, axillary temperature, neutrophil count, CRP and lactate levels are risk factors for VTE in COVID-19 patients.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11739-022-03002-z.

Venous thromboembolism in COVID-19 patients and prediction model: a multicenter cohort study

BackgroundPatients with COVID-19 infection are commonly reported to have an increased risk of venous thrombosis. The choice of anti-thrombotic agents and doses are currently being studied in randomized controlled trials and retrospective studies. There exists a need for individualized risk stratification of venous thromboembolism (VTE) to assist clinicians in decision-making on anticoagulation. We sought to identify the risk factors of VTE in COVID-19 patients, which could help physicians in the prevention, early identification, and management of VTE in hospitalized COVID-19 patients and improve clinical outcomes in these patients.MethodThis is a multicenter, retrospective database of four main health systems in Southeast Michigan, United States. We compiled comprehensive data for adult COVID-19 patients who were admitted between 1st March 2020 and 31st December 2020. Four models, including the random forest, multiple logistic regression, multilinear regression, and decision trees, were built on the primary outcome of in-hospital acute deep vein thrombosis (DVT) and pulmonary embolism (PE) and tested for performance. The study also reported hospital length of stay (LOS) and intensive care unit (ICU) LOS in the VTE and the non-VTE patients. Four models were assessed using the area under the receiver operating characteristic curve and confusion matrix.ResultsThe cohort included 3531 admissions, 3526 had discharge diagnoses, and 6.68% of patients developed acute VTE (N = 236). VTE group had a longer hospital and ICU LOS than the non-VTE group (hospital LOS 12.2 days vs. 8.8 days, p < 0.001; ICU LOS 3.8 days vs. 1.9 days, p < 0.001). 9.8% of patients in the VTE group required more advanced oxygen support, compared to 2.7% of patients in the non-VTE group (p < 0.001). Among all four models, the random forest model had the best performance. The model suggested that blood pressure, electrolytes, renal function, hepatic enzymes, and inflammatory markers were predictors for in-hospital VTE in COVID-19 patients.ConclusionsPatients with COVID-19 have a high risk for VTE, and patients who developed VTE had a prolonged hospital and ICU stay. This random forest prediction model for VTE in COVID-19 patients identifies predictors which could aid physicians in making a clinical judgment on empirical dosages of anticoagulation.

Clinical Characteristics of Venous Thromboembolism in COVID-19 Patients Admitted to the Intensive Care Unit

Clinical Characteristics of Venous Thromboembolism in COVID-19 Patients Admitted to the Intensive Care Unit

Prediction of Symptomatic Venous Thromboembolism in Covid-19 Patients: A Retrospective Comparison of Caprini, Padua, and IMPROVE-DD Scores

Previously, we reported high predictability of the Caprini score for symptomatic venous thromboembolism (VTE) in coronavirus 2019 (COVID-19) patients. This analysis aimed to compare the Caprini score with the Padua and IMPROVE-DD scores in the same cohort.

Anticoagulation practices and venous thromboembolism in COVID-19 patients in a Philippine tertiary hospital

Funding AcknowledgementsType of funding sources: None.INTRODUCTIONCOVID-19 poses an increased risk for thrombosis and initiation of prophylactic anticoagulation has been shown to have mortality benefit in earlier studies. However, the use of full dose anticoagulation as prophylaxis and evidence of the efficacy and safety of anticoagulation on COVID-19 patients remains to be a topic of interest. This study aimed to explore the aspects of anticoagulation applied in a tertiary hospital in the Philippines and to further elucidate on its outcomes and development of complications among COVID-19 patients.METHODSIn this retrospective, observational study, we collected data from the case record forms of 945 patients with COVID-19 from two tertiary centers. Patients given anticoagulant therapy were classified as treated with standard, intermediate and therapeutic dose anticoagulation. The incidence of mortality and venous thromboembolism (VTE) among the three groups were compared as well as the risk for bleeding complications. Categorical variables were analyzed using the Chi-squared test and logistic regression analysis was done to quantify odds for mortality and complications among the treatment groups.RESULTSAmong available agents, Enoxaparin was the anticoagulant of choice in 96.1% of cases. The percentage of patients given anticoagulation was noted to increase with increasing severity. Overall, there were 168 (17.8%) inpatient deaths wherein 128 received anticoagulation. 51.3% of those who received therapeutic anticoagulation were intubated at any time during their hospital stay (p value 0.00). In-hospital survival for patients given prophylactic anticoagulation was 78.3% with the highest mortality among patients given therapeutic anticoagulation at 53.8%. Using binary logistic regression, there was increasing odds of mortality as anticoagulant dosage increased with an odds ratio of 2.818 for therapeutic anticoagulation (p = 0.00, b = 1.036). There was significantly lower incidence of pulmonary embolism and among patients given standard prophylactic therapy. The odds of incurring VTE (OR = 3.38, p = 0.001) and PE (OR = 4.315, p = 0.000) were found to increase as dosage increased. Major bleeding after given anticoagulant therapy was recorded in 4.7% of patients. Although half of the patients who presented with bleeding were given standard dose prophylaxis, the incidence of bleeding was highest within the intermediate dose category at 9.2%.CONCLUSIONTherapeutic dose anticoagulation was associated with higher odds of mortality. The incidence of recorded venous thromboembolism was low but still showed increasing odds as dosage of anticoagulation increased. In lieu of these findings, we recommend that therapeutic dose anticoagulation be given with caution to patients diagnosed with COVID-19, especially among those with severe to critical disease. Patients with the highest risks for VTE and requiring higher anticoagulant dosages should be monitored closely due to higher odds of bleeding. Figure. Figure.

Venous Thromboembolism in COVID-19 Patients During the First and the Second Waves of the Pandemic: Real-Practice Data

Venous Thromboembolism in COVID-19 Patients During the First and the Second Waves of the Pandemic: Real-Practice Data

The Impact of Degree of Anticoagulation on Thrombotic and Other Complications in Hospitalized COVID-19 Patients

Introduction:In hospitalized patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the frequency of venous thromboembolism (VTE) is increased. Retrospective studies suggested that an elevated D-dimer level is associated with increased mortality and predictive of thrombosis in these patients. In the spring of 2020, our institution developed a risk protocol for stratification of hospitalized COVID-19 patients into high, intermediate, or low risk groups, based upon history of thrombosis and D-dimer level. These patients were treated with full-dose anticoagulation, high- or standard-dose prophylaxis, respectively. The goal of this project was to determine the impact of this protocol on VTE frequency, need for intensive care unit (ICU) admission, organ failure and in-hospital mortality while assessing the frequency of hemorrhagic complications when compared to standard prophylactic anticoagulation.Methods:We performed a retrospective chart review of adults hospitalized between March 1 - June 1, 2020 who tested positive for SARS-CoV-2 by nasopharyngeal polymerase chain reaction (PCR). Patients were excluded if they were initially admitted to the ICU. VTE was defined as either a deep vein thrombosis (DVT) on Duplex ultrasound and/or pulmonary embolism (PE) on computed tomography (CT) angiogram. We collected demographic data, medical histories, laboratory and radiologic data on all subjects. Data were analyzed using the Chi Square test and Fisher's Exact Test to establish significant association with clinical outcomes between 3 anticoagulation regimens. Statistical significance was assessed at the p<0.05 level.Results:Data were analyzed from 910 patients; 496 (54.6%) were male and the mean age was 57.8 ± 16.9 years. 419 (46%) subjects were Black, 151 (16.6%) Caucasian, 133 (14.6%) Latinx. Diabetes mellitus (35.3%) and hypertension (59.8%) were common in our cohort as were tobacco (12.6%) and alcohol (20.4%) use. Only 69 (7.6%) were treated with chronic anticoagulation and 216 (23.7%) were on antiplatelet agents. 123 (13.5%) required an ICU transfer and the overall mortality was 5.3%. Most patients, 809 (88.9%), received standard prophylactic anti-coagulation initially (Group A); 32 (3.5%) received high dose prophylaxis (Group B) and 69 (7.6%) received therapeutic dose anticoagulation (Group C). In the entire cohort, 46 (5.1%) developed VTE; 29 (3.6%) in Group A, 2 (6.3%) in Group B, and 15 (22%) in Group C (p<0.0001). ICU admission was required for 102 (12.6%) in Group A, 7 (21.9%) in Group B, and 14 (20.3%) in Group C (p=0.075). 73 ICU patients (8%) required vasopressors, including 57 (7%) in Group A, 6 (18.8%) in Group B and 10 (14.5%) in Group C (p=0.175). 81 ICU patients (8.9%) required mechanical ventilation, including 66 (8.2%) in Group A, 6 (18.8%) in Group B, and 9 (13%) in Group C (p=0.513). One patient in Group B developed an intracerebral hemorrhage. Gastrointestinal hemorrhage occurred in 11 (1.2%) of the cohort; similar rates were observed across treatment arms. The overall in-hospital mortality was 5.3% in this cohort (4.7% in Group A, 12.5% in Group B, and 8.6% in Group C, p=0.064).Conclusion:The rate of VTE in COVID-19 patients receiving any form of anti-coagulation was low. There was an increased rate of VTE, but not rates of ICU admission, mortality, mechanical ventilation nor vasopressor use in those receiving either high dose prophylaxis or therapeutic anticoagulation, suggesting an increased propensity for thrombosis either related to prior thrombotic events or reflected by increased D-dimer levels. These findings need to be confirmed in prospective studies. DisclosuresDiLorenzo: Abbott: Current holder of individual stocks in a privately-held company; Merck & Co: Current holder of individual stocks in a privately-held company; Glaxo Smith Kline: Current holder of individual stocks in a privately-held company. Sloan: Pharmacosmos: Membership on an entity's Board of Directors or advisory committees; Astra Zeneca: Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria; Stemline: Honoraria. Weinberg: Janssen Pharmaceuticals: Other: Serve on data safety monitoring boards; Merck & Co: Current holder of individual stocks in a privately-held company. Klings: CSL Behring: Other: Consultant; Omeros: Other: Consultant; Bluebird Bio: Other: Consultant; Bayer: Research Funding; Novartis: Research Funding; FORM therapeutics: Research Funding.

Does Fibrin Structure Contribute to the Increased Risk of Thrombosis in COVID-19 ICU Patients?

Introduction: SARS-CoV-2 is responsible for a global pandemic, with almost 200 million confirmed cases. SARS-CoV-2 infection can lead to various disease states, from only mild symptoms in the majority of cases to severe disease, which is associated with an increased incidence of venous thromboembolism (VTE). We hypothesized that an altered fibrin network structure contributes to VTE in COVID-19 patients by affecting thrombus stability and fibrinolysis sensitivity. By studying the fibrin network of COVID-19 patients, we aimed to unravel the mechanisms that contribute to the increased risk of VTE in COVID-19 patients.Methods: Between April 2020 and December 2020, we collected plasma samples from patients with COVID-19 admitted to the intensive care unit (ICU) of the Erasmus Medical Center. We included patients with confirmed VTE diagnosed on CT-angiography, and COVID-19 patients without confirmed VTE during ICU admission. Samples were collected on admission to the ICU and after confirmed VTE or at similar time points in ICU patients without confirmed VTE. In addition, we collected plasma from COVID-19 patients at admission to general wards without confirmed VTE and from healthy controls. Clots were formed by mixing citrated plasma with thrombin (final concentration 1 U/ml) and calcium (17 mM). We imaged the clots using stimulated emission depletion (STED) microscopy, a super-resolution technique in which a depletion laser is used to selectively switch off fluorophores surrounding the focal point, thereby increasing the resolution. In these images, fibrin fiber diameters were measured using the Local Thickness plugin of ImageJ. Fiber density was quantified as percentage of area in Z-stacks of confocal microscopy images. Finally, a clot lysis assay based on turbidity was used to determine sensitivity to fibrinolysis (clot lysis time) and clot density (difference between maximum and baseline absorbance). Differences in fibrin network properties between groups were tested using One-Way ANOVA with Bonferroni post-hoc tests and linear regression with and without adjustment for fibrinogen levels.Results: We included 21 COVID-19 ICU patients with confirmed VTE, 20 COVID-19 ICU patients without confirmed VTE, 10 COVID-19 ward patients and 7 healthy controls. Mean age was comparable between the groups, while BMI was higher in COVID-19 patients than in healthy controls (Table 1). Levels of fibrinogen, D-dimer and anti-Xa were significantly higher in COVID-19 ICU patients than in COVID-19 ward patients and healthy controls. FVIII levels were significantly higher in COVID-19 ICU patients than in healthy controls, while FXIII levels were significantly lower.On admission to the ICU, clot density was significantly higher in COVID-19 ICU patients with and without confirmed VTE than in healthy controls (Figure 1 and Table 2). However, after adjustment for fibrinogen levels, this difference disappears. Clot lysis time was significantly longer in clots from COVID-19 ICU patients than in clots from healthy controls, regardless of fibrinogen levels (Table 2). COVID-19 ICU patients with confirmed VTE also showed a significant longer clot lysis time than COVID-19 ward patients. Interestingly, in the clot lysis assay, fibrinolysis did not occur in 25% of COVID-19 ICU patients with VTE versus 9.5% of COVID-19 ICU patients without VTE (Figure 2). This fibrinolysis shutdown was never observed in clots from healthy controls and COVID-19 ward patients. Fibrin fiber diameters were comparable between the groups.In the clots from plasma samples collected at admission to the ICU, there were no differences between COVID-19 ICU patients with and without VTE (Figure 2). However, when comparing clots prepared from plasma collected at the second time point (after VTE or at a similar time point for patients without VTE), we observed significant longer clot lysis times in patients with confirmed VTE (97.4 [88.5-158.8] min) than in patients without confirmed VTE (80.0 [76.0-97.8] min) (p=0.03).Finally, there were no significant changes between clots from plasma before and after VTE or between the two time points in patients without VTE, except for a decreased clot lysis time over time for COVID-19 ICU patients without confirmed VTE.Conclusion: Our results suggest that SARS-CoV-2 infection increases clot density and decreases clot susceptibility to fibrinolysis, and that these changes relate to the severity of the disease. [Display omitted] DisclosuresKruip: Daiichi Sankyo: Research Funding; Bayer: Honoraria, Research Funding.

COVID-19-related laboratory coagulation findings.

The alterations in the hemostatic balance in COVID‐19 patients are strongly disturbed and contribute to a high prothrombotic status. The high rate of venous thromboembolism in COVID‐19 patients goes along with derangements in coagulation laboratory parameters. Hemostasis testing has an important role in diagnosed COVID‐19 patients. Elevated D‐dimer levels were found to be a crucial laboratory marker in the risk assessment of thrombosis in COVID‐19 patients. The diagnostic approach also includes prothrombin time and platelet count. Fibrinogen might give an indication for worsening coagulopathy. Other markers (activated partial thromboplastin time (aPTT), fibrinolysis parameters, coagulation factors, natural anticoagulants, antiphospholipid antibodies and parameters obtained by thromboelastography or thrombin generation assays) have been described as being deranged. These may help to understand the pathophysiology of thrombosis in COVID‐19 patients but have currently no place in diagnosis or management in COVID‐19 patients. For monitoring the heparin anticoagulant therapy, the anti‐Xa assay is suggested, because the severe acute‐phase reaction (high fibrinogen and high factor VIII) shortens the aPTT.