Acute Venous Thromboembolic Events Research Articles

Venous thromboembolism in women with hormone-dependent breast cancer. To continue or discontinue hormonal treatment? Insights from the RIETE registry

IntroductionHormone therapy (HT) for breast cancer is associated with an increased risk of venous thromboembolism (VTE). This study examines the effects of continuing versus discontinuing HT on VTE recurrence, major bleeding, and mortality, after an acute VTE event. MethodsUsing data in the RIETE-registry from March 2001 through September 2021, we calculated incidence rates and rate-ratios (RR) for VTE events in patients on- and off HT. Cox regression models assessed the impact of HT continuation. ResultsAmong 479 women with breast cancer on HT who developed VTE (pulmonary embolism 279, isolated deep vein thrombosis 200), 350 (73 %) continued HT. These women were slightly older (70 ± 13 vs. 67 ± 16 years) than those discontinuing HT, with no significant differences in other baseline characteristics. Over a median follow-up of 294 days, 25 (5.2 %) developed VTE recurrences, 18 (3.7 %) had major bleeding, and 73 (15.2 %) died. Rates of VTE recurrence did not differ significantly between groups (RR: 1.28, 95 % CI 0.44–3.75), except in the first three months post-VTE, where a higher rate was observed in those continuing HT (6.02/100 patients-year vs. no events). On multivariable analysis, HT continuation showed no association with VTE recurrences after adjusting for other thromboembolic risk factors (adjusted hazard ratio [aHR] 1.49, 95 % CI 0.5–4.45). ConclusionContinuing HT after a VTE event in women with breast cancer does not generally affect the long-term risk of VTE recurrences but is associated with a higher risk in the first three months. These findings highlight the need for careful monitoring during this period.

Diagnostic performance of natural language processing in detection of acute cancer VTE.

e19062 Background: The annual incidence of venous thromboembolism (VTE) is roughly 50-fold increased post allogeneic hematopoietic cell transplant (HSCT). Timely detection of VTE events has a significant impact on morbidity and mortality from these events. Manual chart review is commonly used for detection of VTE events; however, this is labor intensive and often not feasible. The International Classification of Diseases, 10th revision (ICD-10) has attempted to codify VTE more easily but has high false positive and false negative rates. Natural language processing (NLP) algorithms have been designed to improve detection of VTE events in electronic medical record systems over the past several years. This study aims to compare the accuracy of our institution’s NLP algorithm to the ICD-10 in detecting extremity VTE/pulmonary embolism (PE) events in hematopoietic stem cell transplant (HSCT) patients. Methods: This study was a retrospective analysis of adult patients who had allogeneic HSCT at MD Anderson between 2016-2020. Patient charts were assessed by three different methods for acute VTE events within 100 days of HSCT (index date). ICD-10 codes and our institution’s NLP algorithm were used separately to identify these VTE events. Afterwards, manual chart review was performed for confirmation. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for the ICD-10, NLP, and the NLP+ICD combination. Results: A total of 1,391 patient charts were analyzed in our study. There were 129 (9.3%) VTE events detected via manual chart review. Three methodologies were used for comparison: the NLP algorithm alone, the ICD code alone, and detection by NLP or ICD. The NLP algorithm alone had the best specificity (98.9%) and PPV (89.4%) of the three methods. The ICD-10 code had a statistically significant decrease in ability to detect acute VTE events compared to the NLP (p<0.001) (Table). Of the 19 VTE events not identified by NLP, all were found in radiology or vascular laboratory reports. Conclusions: Our study shows the overall superior performance of the NLP algorithm, as it had higher sensitivity, specificity, PPV, and NPV compared to the ICD-10, as well as a better specificity and PPV compared to the combination of both methods. Future refinement of the NLP algorithm and combination with other detection methodologies will allow for more accurate detection of VTE in large cohorts. [Table: see text]

Acute venous thromboembolic events in patients with monoclonal gammopathy of undetermined significance: An analysis of the National Inpatient Sample

BackgroundMonoclonal Gammopathy of Undetermined Significance (MGUS) is a premalignant plasma cell disorder which despite being clinically silent carries an increased risk of venous thromboembolism (VTE). We conducted a population-based study to investigate the risk of VTE in these patients. MethodsWe utilized the National Inpatient Sample (NIS) for the year 2016 to compare the incidence of acute VTE between patients who carry the diagnosis of MGUS and those who don't. We excluded hospitalizations with age < 18 years and those that had a diagnosed lymphoma, leukemia, solid malignancy, or other plasma cell dyscrasia. We utilized the ICD-10-CM coding system to search the database for codes of VTE, MGUS, and other comorbid conditions. Multivariate logistic regression models were used for comparative analysis adjusting for demographic characteristics and comorbidities. Baseline comorbidities were described as frequencies and proportions for categorical variables and as medians with interquartile ranges for continuous variables. ResultsA total of 33,115 weighted hospitalizations were included in the MGUS group. These were compared to 27,418,403 weighted hospitalizations without the diagnosis of MGUS. The MGUS group had higher odds of composite venous thromboembolism (adjusted OR 1.33, 95 % CI 1.22–1.44), deep vein thrombosis (adjusted OR 1.46, 95 % CI 1.29–1.65), and pulmonary embolism (adjusted OR 1.22, 95 % CI 1.09–1.37). ConclusionPatients with MGUS had increased odds of developing acute venous thromboembolism compared to patients with no history of MGUS.

COVID-19 Associated 60-Day Acute VTE Events in Hospitalized Patients Can be Predicted By D-Dimer and Prior VTE but Not By Reticulated Platelets

Introduction: COVID-19 is associated with venous thromboembolic (VTE) events, which are predictors for poor outcomes. Beyond d-dimer, there is a dearth of robust studies evaluating the association between VTE and clinical biomarkers. Our prior study established an association between immature platelet fraction (IPF%) and outcomes in COVID-19, specifically mortality and ICU admission. We expand on this by investigating the relationship between IPF% and acute 60-day VTE events in COVID-19 with a larger cohort. Methods: 1238 patients admitted with COVID-19 were analyzed. Various demographic factors and laboratory values, including IPF%, d-dimer, and platelet count were extracted. Charts were reviewed for 60-day VTE events. We assessed the relationship between 60-day VTE events and peak IPF% (IPF% max), lowest value of platelet counts (min platelet count), peak values of immature platelet counts (IPC max). In addition, the study also assessed the relationship between acute 60-day VTE events and average IPF% values (mean IPF%), average platelet counts (mean platelet count), maximum d-dimer (d-dimer max), and average d-dimer (mean d-dimer). Kaplan-Meir curves, Cox proportional hazard, and Cox time-varying covariate models were used to conduct time-to-event analyses to test associations between the selected inflammatory biomarker measures and increased risk of 60-day acute VTE events in our cohort. Results: 110 (9%) patients had an acute VTE event within 60 days of COVID-19 diagnosis. Maximum d-dimer is predictive of acute 60-day VTE events in the Cox proportional hazard model (HR 1.04, 95% CI 1.02-1.06, p<0.01). Additionally, prior VTE event is predictive of acute 60-day VTE event in COVID-19 in the Cox proportional hazard model (HR 2.1, 95% CI 1.4-3.8, p<0.01). However, elevated mean IPF% and IPF% max were higher in patients with VTE (IPF% max 6.4±4.7 vs. 5.1±3.3, p=0.0478; mean IPF% 5.1±3.4 vs.4.7±3.8, p=0.0025) (table 1). In the Cox proportional hazard model, neither mean IPF% nor IPF% max are predictive of VTE. Discussion: Predictive biomarkers for thromboembolism in COVID-19 is an unmet need. This study demonstrates that prior VTE events and maximum d-dimer are predictive of 60-day VTE events but not reticulated (immature) platelets in hospitalized COVID-19 patients. Current prophylactic anticoagulation recommendations in COVID-19 hospitalized patients are broadly based on the patient's clinical acuity, and there is a need for more personalized anticoagulation measures. Use of patient VTE history, clinical scenario, and biomarkers, in conjunction, would provide a more patient-centered approach to anticoagulation practice in hospitalized COVID-19 patients. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Validation of Natural Language Processing for the Identification of Venous Thromboembolism in Radiologic Reports

Background: Natural Language Processing (NLP) is a software driven method of evaluating information of interest. NLP allows for the rapid identification and distinction between disease states, such as acute and chronic venous thromboembolism (VTE), desirable in large datasets. Methods: The aim of this study was to externally validate the use of NLP algorithms developed and internally validated at Mayo Clinic to identify the presence of acute pulmonary embolism (PE) or acute deep vein thrombosis (DVT) from radiologic reports. A dataset of adults who underwent relevant imaging within 90-days after COVID-19 vaccination between 11/1/2020 and 11/1/2021 was used. Verification was achieved by use of two configuration files for radiologic reports (one with CT reports and one with venous duplex ultrasound reports of the extremities) in conjunction with the open-source software SimpleNLP. The data from the NLP analyses were then compared to a blinded determination if the report showed an acute VTE event performed separately by two individuals (DS, LBK). A random sample of 50 reports determined by the NLP algorithm to be positive and 50 negative reports were reviewed. Results: A total of 3,499 images were identified in patients within 90 days of a COVID-19 vaccination (CT scan, n=2431, ultrasound (n=912, lower extremity =790, upper extremity=122). Of the patients who had a chest CT, 96 were identified by the NLP as positive for acute PE and 2335 as negative. Within the random sample of the radiology reports, 49/50 positive and 50/50 negative scans were confirmed, resulting in 100% sensitivity and 98% specificity. The scan falsely identified with acute PE by the NLP noted "A tiny focus of hypoattenuation ...which could represent a small nodule adjacent to the vessel, although a very tiny pulmonary embolus is possible." Of the patients who underwent US for suspected DVT, 100 were identified as positive. Within the random sample, 49/50 ultrasounds were confirmed positive and 50/50 were confirmed negative for acute DVT resulting in a 100% sensitivity and 98% specificity. The ultrasound that was falsely identified with acute DVT said "No definitive central deep venous thrombus in the right upper extremity. Adjacent to the brachial artery courses a hyperechoic structure with no internal flow. It is possibly though less likely an occlusive thrombus in a paired brachial vein." Conclusion: The PE and DVT NLP algorithms have been externally validated to accurately identify acute VTE and exclude chronic VTE events. Ambiguous imaging results led to limited false positive results. The validated NLP algorithms may provide a more accurate identification of acute VTE than ICD-10 codes and can be used in large datasets.

Association of FXI activity with thrombo-inflammation, extracellular matrix, lipid metabolism and apoptosis in venous thrombosis

Animal experiments and early phase human trials suggest that inhibition of factor XIa (FXIa) safely prevents venous thromboembolism (VTE), and specific murine models of sepsis have shown potential efficacy in alleviating cytokine storm. These latter findings support the role of FXI beyond coagulation. Here, we combine targeted proteomics, machine learning and bioinformatics, to discover associations between FXI activity (FXI:C) and the plasma protein profile of patients with VTE. FXI:C was measured with a modified activated partial prothrombin time (APTT) clotting time assay. Proximity extension assay-based protein profiling was performed on plasma collected from subjects from the Genotyping and Molecular Phenotyping of Venous Thromboembolism (GMP-VTE) Project, collected during an acute VTE event (n = 549) and 12-months after (n = 187). Among 444 proteins investigated, N = 21 and N = 66 were associated with FXI:C during the acute VTE event and at 12 months follow-up, respectively. Seven proteins were identified as FXI:C-associated at both time points. These FXI-related proteins were enriched in immune pathways related to causes of thrombo-inflammation, extracellular matrix interaction, lipid metabolism, and apoptosis. The results of this study offer important new avenues for future research into the multiple properties of FXI, which are of high clinical interest given the current development of FXI inhibitors.

Venous thromboembolic events in glioblastoma patients: An epidemiological study.

Background and purposeVenous thromboembolic events (VTEs) are a major complication in cancer patients, and therefore, also in brain cancer patients, anticoagulants are considered appropriate in the treatment of VTEs.MethodsFrequency, risk factors, and treatment of VTEs, as well as associated complications, were assessed in a population‐based cohort of glioblastoma patients in the Canton of Zurich, Switzerland. Correlations between clinical data and survival were retrospectively analyzed using the log‐rank test and Cox regression models.ResultsFour hundred fourteen glioblastoma patients with isocitrate dehydrogenase wild‐type status were identified. VTEs were documented in 65 patients (15.7%). Median time from tumor diagnosis to the occurrence of a VTE was 1.8 months, and 27 patients were diagnosed with VTEs postoperatively (within 35 days; 42.2%). History of a prior VTE was more common in patients who developed VTEs than in those who did not (p = 0.004). Bevacizumab treatment at any time during the disease course was not associated with occurrence of VTEs (p = 0.593). Most patients with VTEs (n = 61, 93.8%) were treated with therapeutic anticoagulation. Complications occurred in 14 patients (23.0%), mainly intracranial hemorrhages (n = 7, 11.5%). Overall survival did not differ between patients diagnosed with VTEs and those who had no VTE (p = 0.139). Tumor progression was the major cause of death (n = 283, 90.7%), and only three patients (1.0%) died in association with acute VTEs.ConclusionsVenous thromboembolic events occurred early in the disease course, suggesting that the implementation of primary venous thromboembolism prophylaxis during first‐line chemoradiotherapy could be explored in a randomized setting.

Drug Use Evaluation of Direct Oral Anticoagulants (DOACs) in Patients With Advanced Cirrhosis.

Objectives: Low molecular weight heparin and vitamin K antagonists are commonly used in cirrhotic patients requiring anticoagulation. However, their monitoring with anti-factor Xa and international normalized ratio (INR) may not be reliable in cirrhosis. Direct oral anticoagulants (DOACs) do not need laboratory monitoring, making these agents a favorable alternative. However, apixaban and rivaroxaban have been avoided in advanced liver disease due to their metabolism in the liver. The purpose of this medication use evaluation was to assess the use of DOACs, specifically apixaban and rivaroxaban, in patients with cirrhosis.Methods: We performed a retrospective, single-center study. Inpatients who had a diagnosis of cirrhosis and received at least one dose of a DOAC (apixaban or rivaroxaban) from April 2016 through June 2020 at our hospital were included in the analysis. Data collected included the reason for admission, Child-Pugh classification, renal function, if this was a home medication or newly started as an inpatient medication, indication, and dosing. The clinical efficacy outcome (new venous thromboembolic event (VTE) or progression of old VTE), and clinical safety outcome (bleeding event) were analyzed.Results: 41 patients with cirrhosis were treated with apixaban or rivaroxaban. Based on the Child-Pugh classification, 29.3% (n=12/41) were placed on a DOAC outside of the FDA prescribing recommendations. In this subpopulation, 8.3% (n=1/12) patients had venous thromboembolism (VTE) and 16.6% (n=2/12) had bleeding events. Overall, 7.3% patients (n=3/41) had VTE and 4.8% (n=2/41) had bleeding events. In the Apixaban for the Initial Management of Pulmonary Embolism and Deep-Vein Thrombosis as First-Line Therapy (AMPLIFY) trial comparing the efficacy and safety profile of apixaban with enoxaparin/warfarin therapy in acute VTE, 2.3% of patients had VTE and 15% had bleeding events.Conclusion: Our study demonstrated that it may be possible to safely use DOACs in patients with advanced cirrhosis. Further studies are needed to evaluate the safety and efficacy of DOACs in this patient population, as our study was limited by the small sample size and its retrospective design.

Plasma levels of platelet‐derived microvesicles are associated with risk of future venous thromboembolism

BackgroundMicrovesicles (MVs) are small double‐membrane encapsulated particles shed from cells. Case‐control studies have reported elevated plasma levels of platelet‐derived MVs (PDMVs) in patients with venous thromboembolism (VTE). However, it is not known whether high PDMV levels is a risk factor or a consequence of the acute VTE event. ObjectivesTo investigate the association between PDMVs in plasma and risk of future incident VTE. MethodsWe performed a population‐based nested case‐control study with 314 VTE cases and 705 age‐ and sex‐matched controls (from The Tromsø Study) to investigate the association between the proportion of PDMVs (PDMVs%) in plasma and risk of future incident VTE. MVs isolated from plasma sampled at baseline (i.e., before VTE) were stained for platelet markers and analyzed by flow cytometry. PDMVs% were defined as the number of PDMVs divided by the total number of MVs. Odds ratios (ORs) with 95% confidence intervals (CI) for VTE risk were estimated across quartiles of PDMVs%. ResultsSubjects with PDMVs% in the highest quartile had an OR for VTE of 1.78 (95% CI: 1.21–2.64) and 1.99 (95% CI: 1.24–3.26) for provoked VTE, compared to those in the lowest quartile. The association was moderately affected by multivariable adjustment for age, sex, body mass index, C‐reactive protein, platelet count, and cancer. The OR for VTE was higher when the time between blood sampling and event was shorter. ConclusionsOur results show that high proportions of PDMVs are associated with future risk of incident VTE and imply a role of platelet activation in the pathogenesis of VTE.

Prognostic Impact of Active Cigarette Smoking on Mortality in Patients with Acute Venous Thromboembolic Events, Findings from Real World Data.

Background and Objectives: The influence of smoking habits on mortality, VTE recurrence, and major bleeding in patients receiving anticoagulant therapy for venous thromboembolism (VTE) has not been consistently evaluated. Materials and Methods: We used data from the RIETE (Registro Enfermedad TromboEmbólica) registry to compare mortality, VTE recurrence, and major bleeding risk in smoking versus non-smoking patients with acute VTE. Results: 50,881 patients (43,426 non-smoking and 7455 smoking patients) were included. After a median follow-up of 8.8 months, 7110 patients died (fatal PE 292 and fatal bleeding 281), 3243 presented VTE recurrence, and 1579 had major bleeding. At multivariate analysis, smoking behavior was associated with a higher hazard of death, (HR: 1.28; 95% CI: 1.19–1.40). The risk of VTE recurrence was marginally increased in smoking patients compared to non-smoking patients (1.14; 95% CI: 1.02–1.27). Major bleeding did not differ in smoking and non-smoking patients (1.15; 95% CI: 0.96–1.38). The presence of cancer did not appear to influence the association between smoking habits and death (HR: 1.34; 95% CI: 1.22–1.47 in cancer patients and HR: 1.23; 95% CI: 1.04, 1.45 in non-cancer patients, respectively) Conclusions: the risk of death after an acute episode of VTE appeared to be higher in smoking than in non-smoking patients and this risk is higher between patients presenting PE at the onset of symptoms.

Abstract TP122: Comparison Of Pharmacologic And Physical Venous Thromboembolism Prophylaxis: A Single Center Descriptive Analysis

Introduction: Recent American Heart Association/American Stroke Association guidelines suggest that physical venous thromboembolism (VTE) prophylaxis modalities are effective at preventing VTE events. Objective: To compare the incidence of VTE events among AIS patients receiving either pharmacologic prophylaxis or physical prophylaxis during hospitalization. Methods: Single center data was retrospectively analyzed among AIS patients who developed DVT or PE during their hospitalization. Patients were selected from January 1, 2016 - December 31, 2020. Inclusion criteria included age 18 and above, AIS patients, diagnosis of acute or chronic VTE events, and exclusive use of physical or pharmacologic VTE prophylaxis modality. We excluded patients who received combined SCD and pharmacologic prophylaxis during hospitalization. Results: Of 5104 patients diagnosed with AIS, 40 patients (0.8%) developed VTE events during their hospitalization. Of these, 29/40 (73%) received pharmacologic VTE prophylaxis and 11/40 (27%) received physical VTE prophylaxis. Of the 3488 patients receiving pharmacologic VTE prophylaxis, 29 (0.8%) developed VTE. Of the 1616 that received physical VTE prophylaxis, 11 (0.7%) developed VTE. Conclusions: Our single center study observed higher rates of VTE events among AIS patients receiving pharmacologic VTE prophylaxis in comparison to physical VTE prophylaxis.

Outcomes of Patients with Extended Anticoagulation Using Low Dose Doacs Compared to Standard Therapeutic Anticoagulation

Background: Reduced or low-dose direct oral anticoagulants (DOACs) have been studied in randomized control trials for the extended prevention of venous thromboembolism (VTE) after 6 months of treatment at the therapeutic doses. The real-world effectiveness as well as utilization of this approach in clinical practice compared to continuing at therapeutic doses is unknown.Aims: Evaluate the efficacy of reduced-dose DOACs compared to standard therapeutic anticoagulation in patients with extended anticoagulation.Methods: Consecutive patients with VTE were identified using the Mayo Clinic VTE Registry from March 1st , 2013 to December 31st, 2020. Patients were followed prospectively for outcomes of VTE recurrence, death, major bleeding and clinically relevant non major bleeding (CRNMB) either in person or by survey. Type of anticoagulation and dose changes were recorded, and progressing to a low dose was treated as an endpoint. In the models relating it to the outcome, it was treated as a time-dependent covariate in the cox models. After completing standard anticoagulation treatment for 3 months with any anticoagulant, patients continuing anticoagulation were divided into two groups: standard therapeutic anticoagulation (any drug) vs those who transitioned to rivaroxaban 10 mg daily or apixaban 2.5mg twice daily any time after 3 months. Patients with recurrent VTE, major or CRNMB during the first 3 months were excluded from further analysis.Results: 219 patients (153 on Apixaban and 66 on Rivaroxaban) were identified in the low dose DOAC and 2521 in the standard anticoagulation group. The mean age was 60.7 years, mean weight was 93.2 Kg and 55.9% were males (Table 1). Patients on low dose DOACs were about the same age and weight compared to standard anticoagulation group. Among all diagnosis categories, patients with active cancer were less likely to be prescribed low dose DOACs (HR 0.56; 95%CI 0.42-0.73; P<0.001), while low dose DOACs prescription was more likely in patients with pulmonary embolism (HR 1.45; 95%CI 1.11-1.89; P=0.007). The median months to start a low dose DOAC after completing the 3 months was 3.1 months with standard deviation of 6.6 months and interquartile range 2.8 months. There was no statistically significant association in the likelihood of going to a low dose group in relation to VTE recurrence (HR 1.36; 95%CI 0.42-4.45; P=0.61) or major bleeding (HR 0.59; 95%CI 0.08-4.37; P=0.61). However, transitioning to low dose DOAC was associated with reduced mortality (HR 0.53; 95%CI 0.35-0.80; P=0.003). Also, patients on low dose DOACs were more likely to have a CRNMB (HR 2.76; 95%CI 1.15-6.62; P=0.02).Conclusion: In this study of patients continuing anticoagulation past 3 months for an initial acute venous thromboembolic event, transitioning to low dose DOACs was not associated with any statistically significant association with VTE recurrence or major bleeding. However, mortality was lower and CRNMB was higher in this unadjusted analysis. Our results show that physicians are not always waiting until 6 months to transition to low doses and low doses are being utilized in cancer patients. Further research is needed to better understand the higher risk for CRNMB identified in this group. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Effectiveness and safety of DOACs for the prevention of recurrent VTE: a prospective cohort study

Abstract Background In the direct oral anticoagulants (DOACs) era, extended anticoagulation after 6–12 months of treatment is an attractive strategy in patients with venous thromboembolism (VTE). Real-life data on the clinical benefit of DOAC over time is lacking. Purpose The aim of this study is to assess the effectiveness and safety of DOACs in patients with acute VTE treated for variable periods. Methods Data on patients with an objective diagnosis of acute VTE treated with DOACs were included in prospective cohort study. Study outcomes were recurrent VTE and major bleeding (ISTH definition). Results Overall, 934 patients were included (mean age 67.0±16.0, male gender 51.4%). Three-hundred and forty-six patients had a deep vein thrombosis (37.0%), 98 (10.5%) had isolated pulmonary embolism and 490 (52.5%) had both. One-hundred and sixty-nine patients (18.1%) had an active cancer, 59 (6.3%) a history of cancer and 365 patients (39.1%) an unprovoked VTE. During DOAC treatment (mean 21.6 months), 7 recurrent VTEs and 25 major bleedings occurred. In 546 and in 98 patients, DOAC was continued with full and reduced doses, respectively. In 290 patients (43.8% unprovoked, 13.8% active cancer, 42.4% associated with non-cancer risk factor), anticoagulants were withdrawn (average treatment duration 8.8 months) and 22 recurrent VTEs occurred over a follow-up off-treatment period of 31.9 months. In these patients, 2 episodes of major bleeding were observed. Overall, 201 patients died; fatal PE occurred in 4 and fatal bleeding in 1 patient. Time course for recurrent VTE according to 2019 ESC risk for recurrence is reported in the Figure. Conclusions In this cohort study, DOACs showed a good risk to benefit profile in the extended phase after an acute VTE event. Funding Acknowledgement Type of funding sources: None. Figure 1. Cumulative incidence of recurrent VTE

A targeted proteomics investigation of the obesity paradox in venous thromboembolism

The obesity paradox, the controversial finding that obesity promotes disease development but protects against sequelae in patients, has been observed in venous thromboembolism (VTE). The aim of this investigation was to identify a body mass–related proteomic signature in VTE patients and to evaluate whether this signature mediates the obesity paradox in VTE patients. Data from the Genotyping and Molecular Phenotyping in Venous ThromboEmbolism Project, a prospective cohort study of 693 VTE patients, were analyzed. A combined end point of recurrent VTE or all-cause death was used. Relative quantification of 444 proteins was performed using high-throughput targeted proteomics technology. Measurements were performed in samples collected during the acute VTE event and at 12-month follow-up. An 11-protein signature (CLEC4C, FABP4, FLT3LG, IL-17C, LEP, LYVE1, MASP1, ST2, THBS2, THBS4, TSLP) for body mass in VTE patients was identified. The signature did not significantly mediate the obesity paradox (change in hazard ratio [HR]: 0.04; likelihood ratio test of nested models = 7.7; P = .74), but its main constituent protein, leptin, was inversely associated with recurrent VTE or death (adjusted HR [95% confidence interval] per standard deviation increase: 0.66 [0.46-0.94]). This relationship was significantly (P = .007) modified by markers of leptin resistance (ie, high body mass index and high circulating matrix metalloproteinase-2 levels). Although the signature did not substantially explain the obesity paradox, leptin appears to be protective against disease recurrence and death in VTE patients. This protective effect was abrogated under conditions of leptin resistance and hence was unrelated to the obesity paradox.

Comorbidities, sequelae, blood biomarkers and their associated clinical outcomes in the Mount Sinai Health System COVID-19 patients.

With the continuing rise of SARS-CoV2 infection globally and the emergence of various waves in different countries, understanding characteristics of susceptibility to infection, clinical severity, and outcomes remain vital. In this retrospective study, data was extracted for 39,539 patients from the de-identified Mount Sinai Health System COVID-19 database. We assessed the risk of mortality based on the presence of comorbidities and organ-specific sequelae in 7,032 CoV2 positive (+) patients. Prevalence of cardiovascular and metabolic comorbidities was high among SARS-CoV2+ individuals. Diabetes, obesity, coronary artery disease, hypertension, atrial fibrillation, and heart failure all increased overall mortality risk, while asthma did not. Ethnicity modified the risk of mortality associated with these comorbidities. With regards to secondary complications in the setting of infection, individuals with acute kidney injury and acute myocardial injury showed an increase in mortality risk. Cerebral infarcts and acute venous thromboembolic events were not associated with increased risk of mortality. Biomarkers for cardiovascular injury, coagulation, and inflammation were compared between deceased and survived individuals. We found that cardiac and coagulation biomarkers were elevated and fell beyond normal range more often in deceased patients. Several, but not all, inflammatory markers evaluated were increased in deceased patients. In summary, we identified comorbidities and sequelae along with peripheral blood biomarkers that were associated with elevated clinical severity and poor outcomes in COVID-19 patients. Overall, these findings detail the granularity of previously reported factors which may impact susceptibility, clinical severity, and mortality during the course of COVID-19 disease.

A Retrospective Review of Outcomes in Intensive Care Unit Patients Infected With SARS-Cov2 in Correlation to Admission Acute Physiologic Assessment and Chronic Health Evaluation II Scores.

IntroductionCoronavirus disease 2019 (COVID-19) has emerged as a global pandemic that has placed an unprecedented burden on intensive care services worldwide. Identification of a reliable risk-stratification tool for COVID-19 patients is necessary for appropriate resource allocation, selection of clinical management pathways, and guidance of goals of care conversations with families and caregivers in the critical care setting. The Acute Physiologic Assessment and Chronic Health Evaluation (APACHE) II scoring system is one of several predictive models used to classify illness severity and estimate mortality risk on admission to the intensive care unit (ICU). Our retrospective study sought to evaluate the prognostic ability of the APACHE II score in COVID-19 patients according to endpoints of mortality and length of stay (LOS) as well as unfavorable clinical outcomes, including development of acute renal failure (ARF) requiring renal replacement therapy (RRT) and acute venous thromboembolic events (VTE).MethodsThis multicenter retrospective cohort study evaluated a randomized sample of 3,102 patients with confirmed COVID-19 disease admitted to the ICU from January 2020 to May 2020. A total of 395 patients with complete data points for appropriate APACHE II score calculation, absence of the preexisting comorbidities end-stage renal disease, and history of VTE were included. Linear and logistic regression models were employed to evaluate primary outcomes of mortality and LOS as well as secondary outcomes of VTE and ARF requiring continuous renal replacement therapy (CRRT) or hemodialysis (HD).Key resultsAmong the 395 patients enrolled, total percent mortality and mean LOS were 37.0% and 12.92 days, respectively. Primary outcome analysis revealed a statistically significant increase in odds of mortality as well as in mean LOS with every additional point increase in APACHE II score from a baseline of zero. Specifically, for every point increase in the APACHE II score, odds of mortality increased by 12% (p value < 0.001), and average LOS increased by 0.2 days (p value < 0.001). In our secondary outcome analysis, 14.43% and 62.2% of the total sample population developed ARF requiring RRT and VTE, respectively. For every additional point increase in APACHE II score from a baseline of zero, odds of requiring CRRT or HD increased by 10% on average (95% CI (1.06, 1.15); p value < 0.001). Similarly, for every additional point increase in the APACHE II score from a baseline of zero, there was a corresponding increase in odds of VTE by 19% (95% CI (1.14, 1.24); p value < 0.001).ConclusionsThe APACHE II score is an effective predictive model of in-hospital mortality and unfavorable clinical outcomes, including prolonged LOS, ARF requiring CRRT or HD, and development of VTE. As therapeutic interventions for COVID-19 evolve, application of this risk-stratification tool may guide clinical management decisions in the critical care setting.

1266: Incidence of Acute Venous Thromboembolic Events Following Administration of Angiotensin II

1266: Incidence of Acute Venous Thromboembolic Events Following Administration of Angiotensin II

Aminotransferases disorders associated with venous thromboembolic events in patients infected with COVID-19

Introduction and objectivesSince the outbreak of the COVID-19 pandemic, increasing evidence suggests that infected patients present a high incidence of venous thromboembolic (VTE) events and elevated aminotransferases (AT).The objective of this work was to evaluate the incidence of aminotransferases disorders in patients infected with COVID-19 and to manage the VTE events associated with elevated AT. Patients or Materials and methodsWe report a retrospective study of 46 patients admitted for COVID-19 infection. Venous duplex ultrasound of lower limbs was performed in all patients at Day 0 and Day 5. All patients had antithrombotic-prophylaxis upon admission using low molecular weight heparin with Enoxaparin. Demographics, comorbidities and laboratory parameters were collected and analyzed. ResultsElevated AT were reported in 28 patients (61%). 10 had acute VTE events of which eight (17.4%) had aminotransferases disorders. They had been treated with curative Enoxaparin. After a follow-up of 15 and/or 30 days, six of them were controlled, and treated with direct oral anticoagulant (DOACs) after normalization of aminotransferases. ConclusionsThe incidence of aminotransferases disorders associated with acute VTE events in patients infected with COVID-19 is significant. The use of DOACs appear pertinent in these patients. Monitoring of the liver balance should therefore be considered at a distance from the acute episode in the perspective of DOACs relay.

Bleeding outcomes in thrombocytopenic acute leukemic patients with venous thromboembolism.

Cancer‐associated thrombosis in acute leukemia patients with severe thrombocytopenia (platelets ≤50 × 109/L) poses a management challenge due to competing risks of bleeding and recurrent thrombosis. A retrospective analysis was conducted to determine the occurrence of clinically relevant bleeding (CRB) rates during treatment for acute venous thromboembolic events (VTE) in thrombocytopenic acute leukemic patients. A cohort of 74 patients were subgrouped into three VTE‐treatment interventions: anticoagulation (n = 24), inferior vena cava filter placement (n = 22), and observation (n = 28). Multivariate analysis found a significant correlation between CRB occurrence and quantity of overall blood transfusions, chemotherapy administration, and relapsed leukemia presentation. There was no difference in the occurrence of CRB between VTE‐treatment subgroups, regardless of initial platelet count at the time of VTE diagnosis. Regarding the hematologic parameters, only the velocity of the platelet count recovery was associated with the risk of bleeding. From this analysis, it appears the trajectory of the platelet count and the factors associated with a slower recovery of it, are the main determinants for the occurrence of hemorrhagic complications during VTE treatment in acute leukemia.

AML-035: Bleeding Outcomes in Thrombocytopenic Acute Leukemia Patients with Venous Thromboembolism at a Comprehensive Cancer Center

Context Cancer-associated thrombosis (CAT) in leukemia patients with severe thrombocytopenia poses a treatment challenge due to competing risks of bleeding and recurrent thrombosis resulting in a narrow therapeutic index for antithrombotic therapies. Objective To determine rates of clinically relevant bleeding (CRB) during management of acute venous thromboembolic event (VTE) in thrombocytopenic acute leukemia patients. Design Retrospective analysis using chart review. Patients Patients (n=74) with acute leukemia admitted to the University of Texas M.D. Anderson Cancer Center, January 2002 - March 2016. Included patients were older than 17 years, with proximal lower extremity deep venous thrombosis and/or pulmonary embolism, and thrombocytopenia (platelet levels ≤50×109/L) on at least two consecutive measures. Patients were sub-grouped into three VTE-treatment interventions: anticoagulation (32.4%), inferior vena cava filter (29.7%), and observation (37.8%). Main outcome measures Rates of CRB and by VTE-treatment intervention group. Association between CRB risk and clinical and laboratory characteristics by multivariate model based on backward model selection. Results Twenty-nine patients (39.2%) suffered CRB during the study (9 had clinically relevant non-major bleeding, 19 had major bleeding, and 1 had both major and non-major bleeding). Patients with relapsed leukemia bled more than those with de novo leukemia (P=0.0294). The use of anticoagulation did not increase the occurrence of CRB (P=0.6035). Use of chemotherapy increased the odds of bleeding by six times (P=0.043). Patients with CRB received more transfusions of platelets (P=0.0012), packed red blood cells (P=0.0017), and fresh frozen plasma (P=0.0573) compared to those who did not bleed. Baseline platelet count was not a significant factor associated to CRB(P=0.35), but the rate of increased platelet counts over time correlated with decreased bleeding chance (P=0.01). Conclusions There was a significant correlation between the occurrence of CRB and quantity of overall blood product transfusions, use of chemotherapy, and relapsed leukemia presentation. There was no difference in rates of CRB between VTE-treatment sub-groups, regardless of platelet count at time of VTE diagnosis. It appears the platelet count trajectory and the factors associated to a slower recovery of it are the main determinants for hemorrhagic complications during VTE treatment in acute leukemia.