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Venous thromboembolism (VTE), which encompasses deep vein thrombosis (DVT) and pulmonary embolism (PE), is a significant cause of morbidity and mortality worldwide. There are many factors, both acquired and inherited, known to increase the risk of VTE. Most of these result in increased risk via several common mechanisms including circulatory stasis, endothelial damage, or increased hypercoagulability. Overall, a risk factor can be identified in the majority of patients with VTE; however, not all risk factors carry the same predictive value. It is important for clinicians to understand the potency of each individual risk factor when managing patients who have a VTE or are at risk of developing VTE. With this, many providers consider performing a thrombophilia evaluation to further define a patient's risk. However, guidance on who to test and when to test is controversial and not always clear. This comprehensive review attempts to address these aspects/concerns by providing an overview of the multifaceted risk factors associated with VTE as well as examining the role of performing a thrombophilia evaluation, including the indications and timing of performing such an evaluation. [ABSTRACT FROM AUTHOR]

Background: The diagnostic strategy for pulmonary embolism (PE) includes a D‐dimer test when PE probability is low or intermediate, but false‐positive D‐dimer results are frequent and can result in an unnecessary computed tomography pulmonary angiogram. The PE rule‐out criteria (PERC) rule excludes PE without D‐dimer testing when pretest probability is <15%. The aim of this study was to assess the safety of the PERC rule strategy in patients included in the Registro Informatizado de la Enfermedad TromboEmbolica venosa (RIETE) registry. Methods: This retrospective cohort study used data from the RIETE registry, an ongoing, international prospective registry of patients with objectively confirmed venous thromboembolism. The primary outcome was the failure rate of the PERC strategy, represented by the proportion of PERC‐negative (PERC‐N) patients with a PE included in the registry. Secondary outcomes were a comparison of the clinical characteristics, treatment strategy, and outcome of PERC‐N versus PERC‐positive (PERC‐P) patients at 3 months. Results: From 2001 to 2021, a total of 49,793 patients with acute PE were enrolled in the RIETE registry. We included 48,903 in the final analysis after exclusion of 890 patients with an undetermined PERC status. Only 346 patients were PERC‐N with a failure rate of 0.7% (95% confidence interval 0.6%–0.8%). PERC‐N patients presented more frequently with chest pain but less often with dyspnea, syncope, or hypotension. They also had subsegmental or segmental PE more frequently, were more often treated with direct oral anticoagulants, and received mechanical or pharmacological thrombolysis less often. In addition, PERC‐N patients had a lower incidence of recurrent deep vein thrombosis, major bleeding, and death attributed to PE during the 3‐month follow‐up. Conclusions: A low failure rate of the PERC rule was observed in the RIETE registry, thus supporting its use to safely identify patients with an unlikely probability of PE. [ABSTRACT FROM AUTHOR]

Background: Chronic immobility is prevalent, especially as people age. However, little is known about venous thromboembolism (VTE) outcomes in this population. Objective: To compare the presentation, treatment, and outcomes in chronically immobile (>8 weeks) patients older vs. younger than 75 who presented with VTE. Design: An observational international registry of patients with VTE. Participants: Patients with acute VTE from the "Registro Informatizado Enfermedad TromboEmbolica" (RIETE) registry who were chronically immobile. Main Measures: Baseline characteristics, presenting signs and symptoms, treatment and outcomes including major bleeding, recurrent VTE, and mortality. Key Results: Among 4612 immobile patients (mean age 75.7 years, 34% male), 2127 (46%) presented with pulmonary embolism (PE). Patients >75 years presented more often with dyspnea (44% vs. 38%) or altered mental status (23% vs. 8.1%) and less often with chest pain (13% vs. 18%). The median duration of anticoagulation was shorter in older compared with younger patients [126 vs. 169 days]. During the first 90 days of anticoagulation, major bleeding (4.0% vs. 2.2%), PE-related death (2.5% vs. 1.1%), and bleeding-related death (0.78% vs. 0.26%) occurred more frequently among older patients. In 3550 patients who received anticoagulation beyond 90 days, older patients had more major bleeding [4.23 vs. 2.21 events per 100 patient years]. After anticoagulation discontinuation, recurrent VTE and major bleeding occurred in 11.8 and 9.25 and 1.49 and 0.69 events per 100 patient years, respectively, both in similar rates in both groups. In multivariable analysis, after stopping anticoagulation, VTE recurrence was inversely associated with long-term facility residence [OR 0.51 (0.28–0.92)], anemia [OR 0.63 (0.42–0.95)], and anticoagulation duration < 90 days [OR 0.38 (0.27–0.54)]. Conclusions: Chronically immobilized patients older than 75 years presenting with VTE experience a high rate of adverse events including major bleeding and recurrent VTE. When considering treatment beyond 90 days, we should account for bleeding, recurrence risk, and associated mortality. [ABSTRACT FROM AUTHOR]

Summary: Predictive tools for major bleeding (MB) using machine learning (ML) might be advantageous over traditional methods. We used data from the Registro Informatizado de Enfermedad TromboEmbólica (RIETE) to develop ML algorithms to identify patients with venous thromboembolism (VTE) at increased risk of MB during the first 3 months of anticoagulation. A total of 55 baseline variables were used as predictors. New data prospectively collected from the RIETE were used for further validation. The RIETE and VTE‐BLEED scores were used for comparisons. External validation was performed with the COMMAND‐VTE database. Learning was carried out with data from 49 587 patients, of whom 873 (1.8%) had MB. The best performing ML method was XGBoost. In the prospective validation cohort the sensitivity, specificity, positive predictive value and F1 score were: 33.2%, 93%, 10%, and 15.4% respectively. F1 value for the RIETE and VTE‐BLEED scores were 8.6% and 6.4% respectively. In the external validation cohort the metrics were 10.3%, 87.6%, 3.5% and 5.2% respectively. In that cohort, the F1 value for the RIETE score was 17.3% and for the VTE‐BLEED score 9.75%. The performance of the XGBoost algorithm was better than that from the RIETE and VTE‐BLEED scores only in the prospective validation cohort, but not in the external validation cohort. [ABSTRACT FROM AUTHOR]

The clinical characteristics and outcomes of patients with coronavirus disease 2019 (COVID-19) who develop pulmonary embolism (PE) in the full spectrum of patient care settings need to be elucidated. The aim of this study was to compare the clinical characteristics, treatment, and 90-day outcomes in patients diagnosed with PE while recovering from COVID-19 in the outpatient setting versus those who were diagnosed with PE while being hospitalized with COVID-19. Data from the international Registro Informatizado de Enfermedad TromboEmbólica (RIETE) registry were used. The major study outcomes were all-cause death, major bleeding, and venous thromboembolism (VTE) recurrences during the first 90 days after PE. From March 2020 to March 2021, 737 patients with COVID-19 experienced acute PE. Of these, 340 (46%) were recovering from COVID-19 as outpatients (267 patients who had been treated at home for COVID-19 and 73 discharged after being hospitalized with COVID-19). Compared with inpatients with COVID-19, those recovering in the outpatient setting upon PE were less likely to be men (odds ratio [OR]: 0.54; 95% confidence interval [CI]: 0.40–0.72) and less likely to have hypertension (OR: 0.55; 95% CI: 0.41–0.74) or diabetes (OR: 0.51; 95% CI: 0.33–0.76). At 90-day follow-up, eight patients (none recovering from COVID-19 as outpatient vs. 2.4% of inpatients with COVID-19) developed recurrent VTE, 34 (1.9 vs. 7.9%) had major bleeding, and 128 (10 vs. 24%) died. On multivariable analysis, inpatients with COVID-19 were at a higher risk of major bleeding (adjusted hazard ratio [HR]: 6.80; 95% CI: 1.52–30.4) or death (adjusted HR: 2.24; 95% CI: 1.40–3.58). In conclusion, using a large multinational registry of patients with COVID-19 who experienced PE, thromboembolic episodes occurring in those recovering from COVID-19 as outpatients were associated with less ominous outcomes than inpatients with COVID-19. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer is a widely heterogeneous disease, and the natural history of patients with cancer-associated thrombosis may differ according to the cancer site. Lung cancer is the most common malignancy, and a leading cause of death. A number of studies in the literature suggest that patients with adenocarcinoma may have a worse outcome than those with squamous or other types of lung cancer. The aim of the current study was to assess the potential impact of lung cancer histology on the incidence rates of VTE recurrences, major bleeding, or death appearing during the course of anticoagulation, in patients with lung cancer and VTE. Our findings, obtained from a large series of consecutive patients with lung cancer and VTE (482 patients), reveal important differences between patients with adenocarcinoma vs. other histologies in their outcomes during anticoagulation. This might likely help to design better therapeutic strategies for patients with lung cancer. Background: In patients with lung cancer and venous thromboembolism (VTE), the influence of cancer histology on outcome has not been consistently evaluated. Methods: We used the RIETE registry (Registro Informatizado Enfermedad TromboEmbólica) to compare the clinical characteristics and outcomes during anticoagulation in patients with lung cancer and VTE, according to the histology of lung cancer. Results: As of April 2022, there were 482 patients with lung cancer and VTE: adenocarcinoma 293 (61%), squamous 98 (20%), small-cell 44 (9.1%), other 47 (9.8%). The index VTE was diagnosed later in patients with squamous cancer than in those with adenocarcinoma (median, 5 vs. 2 months). In 50% of patients with adenocarcinoma, the VTE appeared within the first 90 days since cancer diagnosis. During anticoagulation (median 106 days, IQR: 45–214), 14 patients developed VTE recurrences, 15 suffered major bleeding, and 218 died: fatal pulmonary embolism 10, fatal bleeding 2. The rate of VTE recurrences was higher than the rate of major bleeding in patients with adenocarcinoma (11 vs. 6 events), and lower in those with other cancer types (3 vs. 9 events). On multivariable analysis, patients with adenocarcinoma had a non-significantly higher risk for VTE recurrences (hazard ratio [HR]: 3.79; 95%CI: 0.76–18.8), a lower risk of major bleeding (HR: 0.29; 95%CI: 0.09–0.95), and a similar risk of mortality (HR: 1.02; 95%CI: 0.76–1.36) than patients with other types of lung cancer. Conclusions: In patients with lung adenocarcinoma, the rate of VTE recurrences outweighed the rate of major bleeding. In patients with other lung cancers, it was the opposite. [ABSTRACT FROM AUTHOR]

The Ottawa score (OS) for predicting the risk of recurrent venous thromboembolism (VTE) in cancer patients with VTE may help to guide anticoagulant treatment decisions that will optimize benefit-risk ratios. However, data on its reliability are conflicting. We applied the OS to all cancer patients with VTE enrolled in the prospective multicenter TROPIQUE study who received low-molecular-weight heparin over a 6-month period. Of 409 patients, 171 (41.8%) had a high-risk OS. The 6-month cumulative incidence of recurrent VTE was 7.8% (95%CI 4.2–14.8) in the high-risk OS group versus 4.8% (95%CI 2.6–8.9) in the low-risk OS group (SHR 1.47; 95%CI 0.24–8.55). The Area Under the Receiver Operating Characteristic curve (AUROC) of the OS in identifying patients who developed recurrent VTE was 0.53 (95%CI 0.38–0.65), and its accuracy was 57.9%. Among individual variables included in the OS, only prior VTE was significantly associated with the 6-month risk of recurrent VTE (SHR 4.39; 95% CI 1.13–17.04). When pooling data from all studies evaluating this score for predicting VTE recurrence in cancer patients (7 studies, 3413 patients), the OS estimated pooled AUROC was 0.59 (95%CI 0.56–0.62), and its accuracy was 55.7%. The present findings do not support the use of the OS to assess the risk of recurrent VTE in cancer patients. [ABSTRACT FROM AUTHOR]

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Background: Cellular indices provide integrative information about systemic inflammation status which is readily available from routine laboratory parameters. This study aimed to evaluate the prognostic role of three cellular indices in patients with venous thromboembolism (VTE). Methods: The RIETE registry database was used to determine the association between the baseline neutrophil-to-lymphocyte-ratio (NLR), platelet-to-lymphocyte-ratio (PLR) and systemic-immune-inflammation-index (SII) for 90-day adverse outcomes in patients with acute VTE. Results: From January 2020 to April 2021, 4487 patients with acute VTE were recruited in the RIETE registry. Of these, 2683 presented with symptomatic pulmonary embolism (PE); 283 with incidental PE; 1129 with lower-limb deep vein thrombosis (DVT); 175 with upper-limb DVT; 69 with splanchnic vein thrombosis; 142 with superficial vein thrombosis and 20 with retinal vein thrombosis. Mean values were: NLR 5.9 ± 7.1, PLR 190 ± 158 and SII 1459 ± 2028. During the first 90-days, 38 patients (0.8%) developed recurrent DVT, 45 (1.0%) had recurrent PE, 152 (3.4%) suffered major bleeding, and 484 (11%) died. On multivariable analysis, patients with NLR >4.41 were at an increased risk for major bleeding and patients with NLR >4.96 were at the risk of death, while those with SII >1134.5 were at increased risk for death. Conclusions: This study reports the results of a large cohort to date which evaluate the prognostic value of three cellular indices simultaneously in patients with acute VTE. Results support that none of the three baseline cellular indices were sufficient for prediction of VTE recurrences in acute VTE patients. The patients with higher baseline NLR values were at an increased risk of major bleeding or death, those with high SII values were only at an increased risk for mortality. [ABSTRACT FROM AUTHOR]

Venous thromboembolism (VTE) is common in patients with coronavirus disease-2019 (COVID-19). However, limited data exist on patient characteristics, treatments, and outcomes. To describe the clinical characteristics, treatment patterns, and short-term outcomes of patients diagnosed with VTE during hospitalization for COVID-19. This is a prospective multinational study of patients with incident VTE during the course of hospitalization for COVID-19. Data were obtained from the Registro Informatizado de la Enfermedad TromboEmbólica (RIETE) registry. All-cause mortality, VTE recurrences, and major bleeding during the first 10 days were separately investigated for patients in hospital wards versus those in intensive care units (ICUs). As of May 03, 2020, a total number of 455 patients were diagnosed with VTE (83% pulmonary embolism, 17% isolated deep vein thrombosis) during their hospital stay; 71% were male, the median age was 65 (interquartile range, 55–74) years. Most patients (68%) were hospitalized in medical wards, and 145 in ICUs. Three hundred and seventeen (88%; 95% confidence interval [CI]: 84–91%) patients were receiving thromboprophylaxis at the time of VTE diagnosis. Most patients (88%) received therapeutic low-molecular-weight heparin, and 15 (3.6%) received reperfusion therapies. Among 420 patients with complete 10-day follow-up, 51 (12%; 95% CI: 9.3–15%) died, no patient recurred, and 12 (2.9%; 95% CI: 1.6–4.8%) experienced major bleeding. The 10-day mortality rate was 9.1% (95% CI: 6.1–13%) among patients in hospital wards and 19% (95% CI: 13–26%) among those in ICUs. This study provides characteristics and early outcomes of patients diagnosed with acute VTE during hospitalization for COVID-19. Additional studies are needed to identify the optimal strategies to prevent VTE and to mitigate adverse outcomes associated. [ABSTRACT FROM AUTHOR]

No difference in outcome between therapeutic and preventive anticoagulation in patients with superficial vein thrombosis involving the saphenous-femoral junction Keywords: anticoagulation; saphenous-femoral junction; superficial vein thrombosis (SVT); venous thromboembolism (VTE) EN anticoagulation saphenous-femoral junction superficial vein thrombosis (SVT) venous thromboembolism (VTE) 290 292 3 06/14/22 20220601 NES 220601 Following the demonstration that thrombosis involving the superficial veins of the lower extremities (SVT) is a less benign disease than previously thought,[1] several controlled studies have consistently shown that fondaparinux in preventive doses, low-molecular-weight heparins (LMWHs) in intermediate doses, and rivaroxaban in preventive doses are effective and safe strategies for preventing extension or recurrence of the disease, as well as progression to the deep vein system and migration to the pulmonary circulation.[2][3][4][5] [6] In all these clinical trials, patients with the thrombus head within 3 cm from the saphenous-femoral junction were not eligible for recruitment, as they were perceived as being at a higher risk of venous thromboembolic complications in the absence of an active drug, nor were they in studies addressing the treatment of deep vein thrombosis (DVT) because of the lack of involvement of the deep vein system. Prevention of thromboembolic complications in patients with superficial-vein thrombosis given rivaroxaban or fondaparinux: the open-label, randomised, non-inferiority SURPRISE phase 3b trial. [Extracted from the article]

Edoxaban is used for venous thromboembolism (VTE) treatment. Real‐life data are lacking about its use in long‐term therapy. We aimed to assess the efficacy and the safety of edoxaban for long‐term VTE treatment in a real‐life setting. Patients with VTE included in the Registro Informatizado Enfermedad TromboEmbólica (RIETE) registry, receiving edoxaban 60 or 30 mg daily were prospectively followed up to validate the benefit of using different dosages. The main outcome was the composite of VTE recurrences or major bleeding in patients with or without criteria for dose reduction. Multivariable analysis to identify predictors for the composite outcome was performed. From October 2015 to November 2019, 562 patients received edoxaban for long‐term therapy. Most (94%) of the 416 patients not meeting criteria for dose reduction received 60 mg daily, and 92 patients meeting criteria (63%) received 30 mg daily. During treatment, two patients developed recurrent VTE, six had major bleeding and nine died (2 from fatal bleeding). Among patients not meeting criteria for dose reduction, those receiving 30 mg daily had a higher rate of the composite event (hazard ratio (HR) 8.37; 95% confidence interval (CI) 1.12–42.4) and a significant higher mortality rate (HR 31.1; 95% CI 4.63–262) than those receiving 60 mg. Among patients meeting criteria for dose reduction, those receiving 60 mg daily had no events, and a nonsignificantly higher mortality rate (HR 5.04; 95% CI 0.54–133) than those receiving 30 mg daily. In conclusion, edoxaban seems to be effective and safe for long‐term VTE treatment in real life. Criteria for dose reduction should be reformulated. [ABSTRACT FROM AUTHOR]

In the current era of patient empowerment and precision medicine, access to timely information is critical to decision-making. Unfortunately, we currently lack patient-specific, real-time data about clinical presentation, risk of thrombotic or hemorrhagic events, key risk factors, and adverse outcomes in patients with venous thromboembolism (VTE). Accordingly, the R egistro I nformatizado E nfermedad T rombo E mbólica (RIETE) investigators developed a tool to provide an open-source, real-time graphic representation of VTE-related data derived from over 90 000 patients with confirmed VTE. This information is intended to facilitate discussion in the informed decision-making process. The current article describes the aims, rationale, methods, and ongoing and future efforts of the real-time VTE infographics developed by the RIETE registry collaborators. [ABSTRACT FROM AUTHOR]

The association between inferior vena cava filter (IVC) use and outcome in patients presenting with major bleeding during anticoagulation for venous thromboembolism (VTE) has not been thoroughly investigated. We used the RIETE registry to compare the 30-day outcomes (death, major re-bleeding or VTE recurrences) in VTE patients who bled during the first 3 months of therapy, regarding the insertion of an IVC filter. A propensity score matched (PSM) analysis was performed to adjust for potential confounders. From January 2001 to September 2016, 1065 VTE patients had major bleeding during the first 3 months of anticoagulation (gastrointestinal 370; intracranial 124). Of these, 122 patients (11%) received an IVC filter. Patients receiving a filter restarted anticoagulation later (median, 4 vs. 2 days) and at lower doses (95 ± 52 IU/kg/day vs. 104 ± 55 of low-molecular-weight heparin) than those not receiving a filter. During the first 30 days after bleeding (after excluding 246 patients who died within the first 24 h), 283 patients (27%) died, 63 (5.9%) had non-fatal re-bleeding and 19 (1.8%) had recurrent pulmonary embolism (PE). In PSM analysis, patients receiving an IVC filter (n = 122) had a lower risk for all-cause death (HR 0.49; 95% CI 0.31-0.77) or fatal bleeding (HR 0.16; 95% CI 0.07-0.49) and a similar risk for re-bleeding (HR 0.55; 95% CI 0.23-1.40) or PE recurrences (HR 1.57; 95% CI 0.38-6.36) than those not receiving a filter (n = 429). In VTE patients experiencing major bleeding during the first 3 months, use of an IVC filter was associated with reduced mortality rates.Clinical Trial Registration NCT02832245. [ABSTRACT FROM AUTHOR]

Small studies have suggested differences in demographics and outcomes between left- and right-sided deep vein thrombosis (DVT), and also unilateral versus bilateral DVT. We investigated the clinical presentation and outcomes of patients with DVT based on thrombus sidedness. The authors used the data from the Registro Informatizado Enfermedad Trombo Embólica (RIETE) database (2001-2016) to identify patients with symptomatic proximal lowerextremity DVT. Main outcomes included cumulative 90-day symptomatic pulmonary embolism (PE) and 1-year mortality. Overall, 30,445 patients were included. The majority ofDVTs occurred in the left leg (16,421 left-sided, 12,643 right-sided, and 1,390 bilateral; p < 0.001 for chisquared test comparing all three groups). Comorbidities were relatively similar in those with leftsided and right-sided DVT. Compared with those with left-sided DVT, patients with right-sided DVT had higher relative frequency of PE (26% versus 23%, p < 0.001) and 1-year mortality (odds ratio [OR]: 1.08; 95% confidence interval [CI]: 1.00-1.18). This difference in mortality did not persist after multivariable adjustment (OR: 1.01; 95% CI: 0.93-1.1). Patients with bilateral DVT had a greater burden of comorbidities such as heart failure, and recent surgery compared with those with unilateral DVT (p < 0.001), and higher relative frequency of PE (48%), and 1-year mortality (24.1%).Worse outcomes in patients with bilateralDVTwere attenuated but persisted after multivariable adjustment for demographics and risk factors (OR: 1.64; 95% CI: 1.43-1.87). Patients with bilateral DVT had worse outcomes during and after discontinuation of anticoagulation. There is a left-sided preponderance for proximal lower-extremity DVT. Compared with those with left-sided DVT, patients with right-sided DVT have slightly higher rates of PE. Bilateral DVT is associated with markedly worse short-term and 1-year outcomes. [ABSTRACT FROM AUTHOR]

The usefulness of a diagnostic workup for occult cancer in patients with venous thromboembolism (VTE) is controversial. We used the RIETE (Registro Informatizado Enfermedad Trombo Embólica) database to perform a nested case-control study to validate a prognostic score that identifies patients with unprovoked VTE at increased risk for cancer. We dichotomized patients as having low- (≤2 points) or high (≥3 points) risk for cancer, and tried to validate the score at 12 and 24 months. From January 2014 to October 2016, 11,695 VTE patients were recruited. Of these, 1,360 with unprovoked VTE (11.6%) were eligible for the study. At 12 months, 52 patients (3.8%; 95%CI: 2.9–5%) were diagnosed with cancer. Among 905 patients (67%) scoring ≤2 points, 22 (2.4%) had cancer. Among 455 scoring ≥3 points, 30 (6.6%) had cancer (hazard ratio 2.8; 95%CI 1.6–5; p<0.01). C-statistic was 0.63 (95%CI 0.55–0.71). At 24 months, 58 patients (4.3%; 95%CI: 3.3–5.5%) were diagnosed with cancer. Among 905 patients scoring ≤2 points, 26 (2.9%) had cancer. Among 455 patients scoring ≥3 points, 32 (7%) had cancer (hazard ratio 2.6; 95%CI 1.5–4.3; p<0.01). C-statistic was 0.61 (95%CI, 0.54–0.69). We validated our prognostic score at 12 and 24 months, although prospective cohort validation is needed. This may help to identify patients for whom more extensive screening workup may be required. [ABSTRACT FROM AUTHOR]

Background: Venous thromboembolism (VTE)—including deep vein thrombosis, pulmonary embolism, and cerebral venous sinus thrombosis (CVST)—may occur early after vaccination against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We sought to describe the site, clinical characteristics, and outcomes of VTE after vaccination against SARS-CoV-2. Methods: In a prospective study using the Registro Informatizado de Enfermedad TromboEmbólica (RIETE) platform, patients with VTE 4–30 days after vaccination against SARS-CoV-2 (1 February 2021 through 30 April 2021) were included. VTE patients recruited from the same centers into RIETE in the same months in 2018–2019 were selected as the reference group. All-cause mortality and major bleeding were the main study outcomes. Results: As of 30 April 2020, 102 patients with post-vaccination VTEs had been identified (28 after adenovirus-based vaccination [ChAdOx1 nCov-19; AstraZeneca] and 74 after mRNA-based vaccination [mRNA-1273; Moderna, and BNT162b2; Pfizer]). Compared with 911 historical controls, patients with VTE after adenovirus-based vaccination more frequently had CVST (10.7% vs. 0.4%, p < 0.001) or thrombosis at multiple sites (17.9% vs. 1.3%, p < 0.001), more frequently had thrombocytopenia (40.7% vs. 14.7%, p < 0.001), and had higher 14-day mortality (14.3% vs. 0.7%; odds ratio [OR]: 25.1; 95% confidence interval [CI]: 6.7–94.9) and major bleeding rates (10.3% vs. 1.0%, OR: 12.03, 95% CI: 3.07–47.13). The site of thrombosis, accompanying thrombocytopenia, and 14-day mortality rates were not significantly different for patients with VTE after mRNA-based vaccination, compared with historical controls. Conclusions: Compared with historical controls, VTE after adenovirus-based vaccination against SARS-CoV-2 is accompanied by thrombocytopenia, occurs in unusual sites, and is associated with worse clinical outcomes. [ABSTRACT FROM AUTHOR]