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Background: Exertional dyspnea is a frequently encountered complaint in clinical practice. However, the prevalence of pulmonary embolism (PE) among patients with dyspnea on exertion has not been reported. Objective: The objective of this study was to assess the prevalence of objectively confirmed PE among consecutive patients visiting an emergency department because of recent onset of exertional dyspnea. Methods: Patients aged ≤75 years with recent (

Because of the absence of comparative evidence, current guidelines and product monographs diverge in the dosing of low-molecular-weight heparin (LMWH) for obese patients with venous thromboembolism (VTE). We used the RIETE registry to compare the primary composite outcomes (VTE recurrence, major bleeding, or death) in patients with VTE who weighed >100 kg during LMWH therapy with capped doses of LMWH (18 000 IU/d) vs uncapped doses (>18 000 IU/d). Multivariable logistic regression analysis was used to account for possible confounders. A total of 2846 patients who weighed >100 kg were included: 454 (16%) received capped doses of LMWH, and the remaining 2392 received uncapped doses. Mean (standard deviation) LMWH treatment duration was 14.8 (20.6) and 14.3 (32.3) days, respectively. Thirty-one patients (1.9%) had VTE recurrences, 38 (1.3%) had bleeding episodes, 65 (2.3%) died, and 122 (4.3%) had at least 1 of the composite outcomes. Unadjusted outcome rates revealed that capped dosing was associated with a decrease in the composite outcome (rate ratio, 0.22; 95% confidence interval [CI], 0.04-0.75). Multivariable analysis confirmed that patients who received capped doses had significantly lower rates of the composite outcome (odds ratio, 0.16; 95% CI, 0.04-0.68) while receiving LMWH. These retrospective observational data suggest that capped dosing of LMWH is an acceptable alternative to uncapped dosing based on body weight, given the significantly lower composite event rate of VTE recurrence, major bleeding, and all-cause death.

Background Venous thromboembolism (VTE) represents a relevant cause of morbidity in patients with solid-organ transplant (SOT), but there are scarce data on the management and outcomes in these patients. Methods RIETE is a worldwide, ongoing observational registry of patients with objectively confirmed, acute VTE. We used the RIETE database to compare the clinical characteristics, treatment and outcomes in SOT recipients vs. non-recipients. Results From January 2001 to December 2019, 83,210 patients were enrolled in RIETE. Of these, 329 (0.4%) were SOT recipients: in the kidney 221, liver 41, lung 28 and heart 25. Median duration of anticoagulation was similar in SOT recipients and non-recipients (174 vs. 182 days). During anticoagulation, 1180 patients developed deep vein thrombosis (DVT) recurrences, 1028 pulmonary embolism (PE) recurrences, 2392 had major bleeding, 3119 non-major bleeding and 8157 died. SOT recipients had a higher rate of major bleeding (hazard ratio [HR]: 2.55; 95% CI: 1.62-3.84) and clinically relevant non-major bleeding (HR: 1.94; 95% CI: 1.23-2.93) than non-recipients, with no differences in the rates of DVT recurrences (HR: 0.96; 95% CI: 0.30-2.32), PE recurrences (HR: 1.11; 95% CI: 0.35-2.67) or death (HR: 0.98; 95% CI: 0.67-1.40). On multivariable analysis, only liver transplant recipients were at an increased risk for major bleeding compared to non-recipients (adjusted HR: 3.17; 95% CI: 1.02-9.87). Conclusions Treatment of VTE in SOT recipients is associated with an increased risk of bleeding compared to non-recipients. This is mainly due to the influence of liver transplant recipients. In non-liver SOT recipients, the risk for bleeding was similar to that in non-recipients.

Background: The choice of the imaging modality for diagnosis of pulmonary embolism (PE) could be influenced by provider, patient or hospital characteristics, or over time. However, little is known about the choice of the diagnostic modalities in practice. The aim of this study was to evaluate the variations in the use of imaging modalities for patients with acute PE. Methods: Using the data from Registro Informatizado Enfermedad TromboEmbolica (RIETE), a prospective international registry of patients with venous thromboembolism (March 2001–January 2019), we explored the imaging modalities used in patients with acute PE. The imaging modalities included computed tomography pulmonary angiography, ventilation/perfusion scanning, pulmonary angiography, a combination of these tests, or PE signs and symptoms plus imaging-confirmed proximal deep vein thrombosis but no chest imaging. Results: Among 38 025 patients with confirmed PE (53.1% female, age: 67.3±17 years), computed tomography pulmonary angiography was the dominant modality of diagnosis in all RIETE enrollees (78.2% [99% CI, 77.6–78.7]); including pregnant patients (58.9% [99% CI, 47.7%–69.4%]) and patients with severe renal insufficiency (62.5% [99% CI, 59.9–65.0]). A greater proportion of patients underwent ventilation/perfusion scanning in larger hospitals compared with smaller hospitals (13.1% versus 7.3%, P P Conclusions: In a large multinational PE registry, variations were observed in the use of imaging modalities according to patient or institutional factors and over time. However, computed tomography pulmonary angiography was the dominant modality of diagnosis, even in pregnancy and severe renal insufficiency. The safety, costs, and downstream effects of these tests on PE-related and non-PE-related outcomes warrant further investigation.

Registro Informatizado de Enfermedad Tromboembólica Investigators., [Objective] Overlap exists between the risk factors for coronary artery disease and venous thromboembolism (VTE). However, a paucity of data is available on the incidence of major acute cardiovascular events (MACE) and major adverse limb events (MALE) among patients presenting with VTE. Moreover, it is unknown whether the rate of cardiovascular outcomes differs among patients with unprovoked vs provoked VTE., [Methods] We analyzed the data from 2009 to 2017 in the Registro Informatizado de Enfermedad Tromboembólica registry, an ongoing, multicenter, international registry of consecutive patients with a diagnosis of objectively confirmed VTE. The query was restricted it to patients with data entry for the arterial outcomes. The baseline prevalence of coronary artery disease risk factors was compared between patients with provoked (ie, immobility, cancer, surgery, travel >6 hours, hormonal causes) and unprovoked VTE. After the initial VTE event, we followed up patients for the composite primary outcome of incident MACE (ie, stroke, myocardial infarction, unstable angina) and/or MALE (ie, major limb events). We used the χ2 test for baseline associations and a Cox proportional hazard for multivariate analysis. We used IBM SPSS, version 24 (IBM Corp, Armonk, NY) for statistical analysis. A P value of, [Results] We analyzed the data from 41,259 patients with VTE, of whom 22,633 (55.6%) had experienced a provoked VTE. During follow-up, the patients with provoked VTE were more likely to develop MACE or MALE than were patients with unprovoked VTE (hazard ratio [HR], 1.3; 95% confidence interval [CI], 1.1-1.5). The association of arterial events with recent immobility (HR, 1.4; 95% CI, 1.5-12.1) and cancer (HR, 1.7; 95% CI, 1.4-1.9) was strong. After adjusting for multiple conventional cardiovascular risk factors, provoked VTE, compared with unprovoked VTE, was significantly associated with an increased hazard for MACE (HR, 1.4; 95% CI, 1.1-1.7). Cancer remained a significant adjusted predictor for both MACE (HR, 1.7; 95% CI, 1.4-2.1) and MALE (HR, 2.1; 95% CI 1.01-4.6) in those with provoked VTE., [Conclusions] Among patients with VTE, provoked cases, specifically those with cancer-associated VTE, have an increased risk of major arterial events.

Background The recanalization rate in patients with deep venous thrombosis (DVT) of the legs treated with the direct oral anticoagulants (DOAC) is unknown. Methods In an Italian cohort, we investigated the rate of residual vein thrombosis (RVT) after three and/or six months in 352 patients with proximal DVT who had been treated with the DOACs as a stand-alone therapy or lead-in parenteral anticoagulants, and compared it to that recorded in a historical cohort of 1094 patients in which vitamin K antagonists (VKAs) had been employed. In both cohorts, RVT was defined as the ultrasound persistence of thrombotic material resulting in a diameter of at least 4 mm of incompressibility of the proximal veins. Results RVT was detected in 143 patients treated with DOACs (41.2%) after three months and in 58 patients (21.1%) after six months; the corresponding figure in patients treated with conventional anticoagulation was 52.3% and 54.5%, respectively. After adjusting for the baseline characteristics, the odds ratio of RVT in patients treated with the DOACs as compared with those treated with conventional anticoagulation was 0.63 (95% CI, 0.48–0.81) after three months, and 0.17 (95% CI; 0.11–0.26) after six months. Conclusions In patients with proximal DVT treated with the DOACs, the persistence of ultrasound detectable RVT is likely to occur less frequently than in patients treated with conventional anticoagulation. These results may have implications for the prognosis of patients with DVT.

Background We hypothesized that the clinical course of venous thromboembolism in patients with active cancer may differ according to the specificities of primary tumor site. Aim and Methods We used data from RIETE (international registry of patients with venous thromboembolism) to compare the clinical venous thromboembolism-related outcomes during the course of anticoagulation in patients with one of the 4 more frequent cancers (breast, prostate, colorectal, or lung cancer). Results As of September 2014, 3947 cancer patients were recruited, of whom 938 had breast, 629 prostate, 1189 colorectal, and 1191 lung cancer. Overall, 55% had metastatic disease (42%, 36%, 53%, and 72%, respectively). During the course of anticoagulant therapy (mean duration, 139 days), the rate of thromboembolic recurrences was similar to the rate of major bleeding in patients with breast (5.6 [95% confidence interval (CI), 3.8-8.1] vs 4.1 [95% CI, 2.7-5.9] events per 100 patient-years) or colorectal cancer (10 [95% CI, 7.6-13] vs 12 [95% CI, 9.4-15] per 100 patient-years). In contrast, in patients with prostate cancer, the rate of venous thromboembolic recurrences was half the rate of major bleeding (6.9 [95% CI, 4.4-10] vs 13 [95% CI, 9.2-17] events per 100 patient-years), whereas in those with lung cancer, the rate of thromboembolic recurrences was twofold higher than the rate of major bleeding (27 [95% CI, 22-23] vs 11 [95% CI, 8.6-15] per 100 patient-years). Conclusions Significant differences in the clinical profile of venous thromboembolic-related outcomes were observed according to the site of cancer. These findings suggest the development of cancer-specific anticoagulant strategies as an area for further research.

BackgroundD-dimer levels measured during and after vitamin K antagonist withdrawal may be used in clinical practice to assess the individual risk of recurrent venous thromboembolism. Currently, direct oral anticoagulants (DOACs) are frequently used in venous thromboembolism treatment; however, their pharmacokinetics and pharmacodynamics characteristics are completely different than vitamin K antagonists. The present study aimed at comparing the results of D-dimer levels during and after anticoagulation withdrawal in patients with venous thromboembolism treated with DOACs or warfarin.Material and methodsD-dimer levels were measured in 527 patients ("cases") during DOACs treatment (T0) and after 15 (T15), 30 (T30), 60 (T60) and 90 (T90) days after their discontinuation and in 527 patients ("controls") enrolled in the DULCIS study (all treated with warfarin), matched for sex, age (+/-3 y), type of D-dimer assay and site of venous thromboembolism. Both cases and controls received anticoagulant treatment after a first venous thromboembolism event that was unprovoked or associated with weak risk factors.ResultsThe rate of positive D-dimer results was significantly higher in cases than in controls at T0 (10.8% vs 5.1%, p = 0.002) and at T30 (18.8% vs 11.8%, p = 0.019), as well as at the other time-points, though not statistically significant.ConclusionD-dimer levels during and after stopping an anticoagulant treatment for a venous thromboembolism episode differ between patients treated with a DOAC than in those treated with warfarin. Specifically designed prospective studies are warranted to reassess the use of D-dimer as predictor of the risk of recurrent venous thromboembolism in patients treated with DOACs.

Background The optimal long-term strategy for preventing recurrent venous thromboembolism (VTE) in patients with deep-vein thrombosis (DVT) is uncertain. Methods In 620 consecutive outpatients with a first proximal DVT who had completed at least three months of anticoagulation (unprovoked in 483, associated with minor risk factors in 137), the ultrasound presence of residual vein thrombosis (RVT) was assessed and defined as an incompressibility of at least 4 mm. In 517 patients without RVT and with negative D-dimer, anticoagulation was stopped and D-dimer was repeated after one and three months. Anticoagulation was resumed in 63 of the 72 patients in whom D-dimer reverted to positivity. Results During a mean follow-up of three years, recurrent VTE developed in 40 (7.7%) of the 517 patients, leading to an annual rate of 3.6% (95% CI, 2.6 to 4.9): 4.1% (95% CI, 2.9 to 5.7) in individuals with unprovoked DVT, and 2.2% (95% CI, 1.1 to 4.5) in those with DVT associated with minor risk factors. Of the 233 males with unprovoked DVT, 17 (7.3%) developed events in the first year of follow-up. Major bleeding complications occurred in 8 patients while on anticoagulation, leading to an annual rate of 1.2% (95% CI, 0.6 to 2.4). Conclusions Discontinuing anticoagulation in patients with a first episode of proximal DVT based on the assessment of RVT and serial D-dimer leads to an overall annual rate of recurrent VTE lower than 5.0%, which is the rate deemed as acceptable by the Subcommittee on Control of Anticoagulation of the ISTH. However, in males with unprovoked DVT there is room for further improving the long-term strategy of VTE prevention. ( ClinicalTrials.gov number, NCT01285661 ).

We sought to determine the risk factors for subsequent bleeding and recurrent venous thromboembolism (VTE) events following isolated noncatheter-associated upper extremity deep venous thrombosis (non-CA-UEDVT) to better inform future treatment decisions for this group of patients.The RIETE registry (Registro Informatizado de Enfermedad TromboEmbólica [Computerized Registry of Patients with Venous Thromboembolism]) is a prospective international registry of patients with objectively confirmed symptomatic VTE. Patients with a symptomatic, isolated, proximal UEDVT from March 2001 through March 2015 were analyzed. Any patient with an indwelling catheter or pacemaker lead at the DVT site and at the time of thrombosis was considered to have a CA-UEDVT and was excluded. Patient and treatment characteristics such as age, gender, comorbidities, VTE risk factors, treatment drug, and duration were collected. Outcomes examined included recurrent DVT, subsequent pulmonary embolism (PE), and hemorrhage. Multivariate analysis was performed using stepwise logistic regression.Of the 1100 patients who met the study criteria, 580 (53%) were male. The mean age of the patients was 50 ± 20 years, and overall patient survival at 1 year was 85%. Recurrent VTE occurred in 59 patients (5.4%). Of these, 46 patients (4%) had recurrent DVT, 10 (0.9%) had a PE following UEDVT diagnosis, and 3 (0.3%) had both. PE was fatal in three patients (0.3%). Bleeding occurred in 50 patients (4.5%), major bleeding in 19 patients (1.7%), and fatal bleeding in 6 patients (0.5%). On multivariate analysis, malignant disease was associated with VTE recurrence (odds ratio [OR], 2.00; 95% confidence interval [CI], 1.04-3.45; P .04), whereas hemorrhage was associated with age (OR, 1.03; 95% CI, 1.01-1.05; P = .002) and malignant disease (OR, 2.53; 95% CI, 1.34-4.76; P .005). Hemorrhage and recurrent VTE were also significantly associated (OR, 2.79; 95% CI, 1.16-6.76; P .03).PE following non-CA-UEDVT is rare. Malignant disease was associated with VTE recurrence. Age and malignant disease were associated with hemorrhage, and VTE recurrence was associated with hemorrhage. Further prospective studies should be undertaken to best determine length of anticoagulation treatment for the varied populations of patients with UEDVT.

The impact of residual pulmonary obstruction on the outcome of patients with pulmonary embolism is uncertain.We recruited 647 consecutive symptomatic patients with a first episode of pulmonary embolism, with or without concomitant deep venous thrombosis. They received conventional anticoagulation, were assessed for residual pulmonary obstruction through perfusion lung scanning after 6 months and then were followed up for up to 3 years. Recurrent venous thromboembolism and chronic thromboembolic pulmonary hypertension were assessed according to widely accepted criteria.Residual pulmonary obstruction was detected in 324 patients (50.1%, 95% CI 46.2–54.0%). Patients with residual pulmonary obstruction were more likely to be older and to have an unprovoked episode. After a 3-year follow-up, recurrent venous thromboembolism and/or chronic thromboembolic pulmonary hypertension developed in 34 out of the 324 patients (10.5%) with residual pulmonary obstruction and in 15 out of the 323 patients (4.6%) without residual pulmonary obstruction, leading to an adjusted hazard ratio of 2.26 (95% CI 1.23–4.16).Residual pulmonary obstruction, as detected with perfusion lung scanning at 6 months after a first episode of pulmonary embolism, is an independent predictor of recurrent venous thromboembolism and/or chronic thromboembolic pulmonary hypertension.

The latest developments in emergency medicine (EM) have introduced new typologies of patients that have not been taken into account in previous studies of venous thromboembolism (VTE) risk. The aim of the current study was to evaluate by comparing the main international risk scores whether different perceptions of VTE risk exist in internal medicine (IM) departments and in EM departments. This cross-sectional observational study involved 23 IM and 10 EM departments of 21 different hospitals. The patient data were collected by physicians who were blinded to the purpose of the study. The data were analyzed using the main international risk scores. We analyzed 742 patients, 222 (30%) hospitalized in EM departments and the remaining 520 (70%) in IM departments. We found that fewer patients at risk for VTE were treated with low-molecular-weight heparin (LMWH) in EM departments than in IM departments. Moreover, there was significant statistical difference in the use of LMWH between IM and EM departments when the Padua score and immobilization criteria were used to assess the risk. The infrequent use of LMWH in EM patients may have several causes. For example, in EM departments, treatment of acute illness often takes higher priority than VTE risk evaluation. Moreover, immobilization criteria cannot be evaluated for all EM patients because of the intrinsic time requirements. For the aforementioned reasons, we believe that a different VTE risk score is required that takes into account the peculiarities of EM, and establishing such a score should be the object of future study.

Introduction: The clinical characteristics, treatment strategies and outcome of patients with venous thromboembolism (VTE) may vary from country to country. Materials and methods: The RIETE (Registro Informatizado su la Enfermedad TromboEmbolica) is an ongoing, prospective registry of consecutive patients with acute, objectively confirmed, symptomatic VTE. Our aim was to assess the influence of surgery and immobility for non-surgical reasons on 3-month outcomes of all Italian patients registered in the RIETE. Results: Through July 2008, 21,397 patients with acute VTE were registered in the RIETE. Of these, 896 (4.2%) were Italian, and 360 (40%) presented with pulmonary embolism (PE). Overall, 137 (15%) developed VTE after surgery; 156 (17%) developed VTE after >4 days of immobility, and 603 (67%) developed VTE in the absence of surgery or immobility. Most patients (83%) received initial therapy with low-molecular-weight heparin; 15% received unfractionated heparin. For long-term therapy, 63% of patients received vitamin K antagonists. The incidence of fatal PE during the first 3 months of therapy was 1.5% for patients with postoperative VTE, 7.7% for who developed VTE after immobility, and 1.2% for the remaining patients. The incidence of fatal bleeding among these patients was 1.5%, 1.9% and 0.3%, respectively. Of the 137 patients with postoperative VTE, 61% had received VTE prophylaxis. Of the 156 patients with recent immobility, 24% had received VTE prophylaxis. Conclusions: VTE arising after a period of immobility was associated with the highest rates of fatal PE and fatal bleeding during the first 3 months of therapy. The use of thromboprophylaxis in this population should be improved.

Overuse of thromboprophylaxis is not an infrequent behavior in internal medicine. However, differently from underuse, overuse of thromboprophylaxis is rarely taken into account, and only few studies have addressed this issue. The purpose of our study was to try to understand the reasons behind this phenomenon.Using data from the TEVERE study, we evaluated 279 patients hospitalized in 21 hospitals of the Lazio Region in Italy. Only patients who were negative to major risk scores as established in the scientific literature were included. We assessed the frequency of thromboprophylaxis in acutely ill medical patients hospitalized in emergency and internal medicine wards, and we performed a comparative analysis for each risk factor among patients who received or not received thromboprophylaxis.Forty-seven patients (16.5%) with negative risk scores were given thromboprophylaxis during hospitalization. On backward stepwise logistic regression analysis, severe infection (odds ratio [OR] 2.31; 95% confidence interval [CI] 1.25-4.35) and chronic venous insufficiency (OR 3.02; 95% CI 1.96-4.67) were found to be the strongest predictors of the use of thromboprophylactic treatment with heparin. The subgroup of patients who did not exhibit risk factors was also analyzed, and age was found to be the main factor in the decision-making process regarding heparin administration in the absence of other risk factors (74.9 ± 11.8 vs 63.7 ± 18.1, p=0.002).Our findings suggest that thromboprophylaxis is associated with considerable uncertainty, which results in its overuse. Further research is needed to better understand thromboembolic risk factors in hospitalized medical patients.