Background
Age is a major risk factor for venous thromboembolism (VTE), yet patients aged ≥90 years are under‐represented in clinical trials of anticoagulant therapy. The objectives were to describe ...and compare patient clinical characteristics, treatments, and outcomes (VTE recurrence, bleeding, and mortality) during the first 3 months of anticoagulation between VTE patients aged ≥90 years and those aged <90 years.
Methods
We analyzed data from the Registro Informatizado Enfermedad TromboEmbὀlica (RIETE), an ongoing global observational registry of patients with objectively confirmed acute VTE.
Results
From January 2001 to October 2022, 96,701 patients were registered in RIETE, of whom 3262 (3.4%) were aged ≥90 years. Patients aged ≥90 years were less likely to be men, and to have experienced cancer or recent surgery, but more likely to manifest immobility, chronic heart failure, anemia, renal insufficiency, or dementia than those aged <90 years. Most (99.6%) patients aged ≥90 years were receiving anticoagulant therapy. During the first 3 months, 26 patients aged ≥90 years developed VTE recurrences, 116 experienced major bleeding, and 564 died. Among patients initially presenting with pulmonary embolism (PE), deaths due to PE exceeded those due to fatal bleeding (76 vs. 19). Among those initially presenting with isolated deep‐vein thrombosis (DVT), it was the reverse (2 vs. 11 deaths).
Conclusions
In patients aged ≥90 years, the difference in the outcome of anticoagulant treatment depending on the initial presentation of VTE could suggest a need for different management approaches. Clinical trials evaluating the optimal duration of anticoagulation according to initial VTE presentation are warranted to limit excess deaths in this particular population.
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.
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.
Aims
Little is known about the prognosis of patients with massive pulmonary embolism (PE) and its risk of recurrent venous thromboembolism (VTE) compared with non‐massive PE, which may inform ...clinical decisions. Our aim was to compare the risk of recurrent VTE, bleeding, and mortality after massive and non‐massive PE during anticoagulation and after its discontinuation.
Methods and results
We included all participants in the RIETE registry who suffered a symptomatic, objectively confirmed segmental or more central PE. Massive PE was defined by a systolic hypotension at clinical presentation (<90 mm Hg). We compared the risks of recurrent VTE, major bleeding, and mortality using time‐to‐event multivariable competing risk modeling. There were 3.5% of massive PE among 38 996 patients with PE. During the anticoagulation period, massive PE was associated with a greater risk of major bleeding (subhazard ratio sHR 1.72, 95% confidence interval CI 1.28–2.32), but not of recurrent VTE (sHR 1.15, 95% CI 0.75–1.74) than non‐massive PE. An increased risk of mortality was only observed in the first month after PE. After discontinuation of anticoagulation, among 11 579 patients, massive PE and non‐massive PE had similar risks of mortality, bleeding, and recurrent VTE (sHR 0.85, 95% CI 0.51–1.40), but with different case fatality of recurrent PE (11.1% versus 2.4%, P = .03) and possibly different risk of recurrent fatal PE (sHR 3.65, 95% CI 0.82–16.24).
Conclusion
In this large prospective registry, the baseline hemodynamic status of the incident PE did not influence the risk of recurrent VTE, during and after the anticoagulation periods, but was possibly associated with recurrent PE of greater severity.
Background
Patients with venous thromboembolism (VTE) secondary to transient risk factors may develop VTE recurrences after discontinuing anticoagulation. Identifying at‐risk patients could help to ...guide the duration of therapy.
Methods
We used the RIETE database to assess the prognostic value of d‐dimer testing after discontinuing anticoagulation to identify patients at increased risk for recurrences. Transient risk factors were classified as major (postoperative) or minor (pregnancy, oestrogen use, immobilization or recent travel).
Results
In December 2018, 1655 VTE patients with transient risk factors (major 460, minor 1195) underwent d‐dimer measurements after discontinuing anticoagulation. Amongst patients with major risk factors, the recurrence rate was 5.74 (95% CI: 3.19–9.57) events per 100 patient‐years in those with raised d‐dimer levels and 2.68 (95% CI: 1.45–4.56) in those with normal levels. Amongst patients with minor risk factors, the rates were 7.79 (95% CI: 5.71–10.4) and 3.34 (95% CI: 2.39–4.53), respectively. Patients with major risk factors and raised d‐dimer levels (n = 171) had a nonsignificantly higher rate of recurrences (hazard ratio HR: 2.14; 95% CI: 0.96–4.79) than those with normal levels. Patients with minor risk factors and raised d‐dimer levels (n = 382) had a higher rate of recurrences (HR: 2.34; 95% CI: 1.51–3.63) than those with normal levels. On multivariate analysis, raised d‐dimers (HR: 1.74; 95% CI: 1.09–2.77) were associated with an increased risk for recurrences in patients with minor risk factors, not in those with major risk factors.
Conclusions
Patients with raised d‐dimer levels after discontinuing anticoagulant therapy for VTE provoked by a minor transient risk factor were at an increased risk for recurrences.
The association between elevated liver enzymes or FIB-4 (fibrosis index 4) and outcome in patients with venous thromboembolism (VTE) has not been evaluated. Data from patients in RIETE (
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mbólica) were used to assess the association between elevated liver enzymes or FIB-4 levels and the rates of major bleeding or death in apparent liver disease-free patients with acute VTE under anticoagulation therapy. A total of 6206 patients with acute VTE and without liver disease were included. Of them, 92 patients had major bleeding and 168 died under anticoagulation therapy. On multivariable analysis, patients with elevated liver enzymes were at increased mortality risk (HR: 1.58; 95% CI: 1.10–2.28), while those with FIB-4 levels > 2.67 points were at increased risk for major bleeding (HR: 1.69; 95% CI: 1.04–2.74). Evaluation of liver enzymes and FIB-4 index at baseline in liver disease-free patients with VTE may provide additional information on the risk for major bleeding or death during anticoagulation.
•In a RIETE registry analysis of 103 818 patients with VTE, 20.3% were tested for IT, showing a substantial variance in outcomes.•A thoughtful IT testing approach should consider patients’ VTE risk ...factors and comorbidities.
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Inherited thrombophilia (IT) workup is commonly pursued in patients with venous thromboembolism (VTE). Recent American Society of Hematology guidelines recommend a selective approach to IT testing, nevertheless, evidence on whether thrombophilia testing can actually improve patient-important outcomes through tailored management is limited. Data from the large, prospective Registro Informatizado de Enfermedad TromboEmbólica (RIETE) registry were analyzed to compare VTE risk factors, management, and outcomes between patients who were tested for IT and untested patients, during anticoagulant treatment and after its discontinuation. Among 103 818 patients enrolled in RIETE, 21 089 (20.3%) were tested for IT, 8422 (8.1%) tested positive, and 82 729 (79.7%) were not tested. IT testing was more frequent in patients with VTE provoked by minor risk factors and less common in those with major risk factors such as surgery or active cancer. Choices of anticoagulant treatment did not differ based on IT testing results. Untested patients exhibited inferior outcomes across all VTE categories, with higher rates of VTE recurrence, major bleeding, mortality, and notably, cancer-related mortality. After treatment discontinuation, IT-negative patients with surgically provoked VTE showed lower recurrence rates. For immobilization-related VTE as well as in estrogen-related VTE, no significant differences in recurrence rates were observed between IT-negative and IT-positive patients. However, IT-negative patients with pregnancy or postpartum-related VTE had significantly lower recurrence rates. Patients with unprovoked VTE, particularly those testing positive for IT, had high recurrence rates after treatment. These findings underscore the complex role of IT testing in managing VTE, supporting personalized treatment strategies that consider VTE risk factors and comorbidities. The trial was registered at www.clinicaltrials.gov as #NCT02832245.
Abstract Thin melanomas are recognized and captured by clinicians at an alarming rate, whereas thick melanomas remain underrecognized. Improved recognition of thick melanomas will require further ...understanding of their clinical and histologic characteristics at various stages of development because emerging data suggest that the thin melanomas being captured today may not represent the forerunners of the thick melanomas. In this retrospective analysis, pathology requisition forms from melanomas diagnosed by histopathology were examined for submitted clinical diagnosis, patient characteristics, melanoma thickness, and biopsy method. Three hundred eighty-five melanomas were identified from 2003 to 2011. Most lesions (71.7%) were clinically suspected to be melanocytic. The mean depth in this group was 0.62mm. Of the unsuspected cases (28.3%), the most common submitted diagnoses were basal cell carcinomas and seborrheic keratoses, consistent with previous reports. The mean depth in the unsuspected group was 1.64mm, and more frequently extended to the deep margin (51.8% vs 25.4% of the time). Shave biopsy was the overwhelming preferred method of biopsy (79.5% overall). Compared with thin melanomas, thick melanomas are underrecognized by physicians due to their lack of characteristic morphologic features; consequently, they are more frequently associated with suboptimal biopsies.
Patent foramen ovale (PFO) is associated with cryptogenic stroke, migraine headache, decompression sickness, and platypnea-orthodeoxia syndrome. Patients undergoing transesophageal echocardiography ...are often hypovolemic from preprocedural fasting and might not demonstrate right to left shunting owing to insufficient right atrial pressure generation, despite provocative maneuvers. We hypothesized that volume replenishment with saline loading could potentially unmask a PFO by favorably modulating the interatrial pressure gradient. Our study sought to examine the role of pre- or intraprocedural intravenous fluid replenishment on PFO detection during transesophageal echocardiography. A total of 103 patients were enrolled. An initial series of bubble injections was performed unprovoked and then with provocative maneuvers such as the Valsalva maneuver and coughing. The patients were then given a rapid 500 ml saline bolus, and the same sequence of bubble injections was repeated. The presence, type, and magnitude of the right to left shunts were noted before and after the saline bolus. The detection rate of PFO increased from 10.6% to 26.2% after saline loading without any provocative maneuvers. When combined with provocative maneuvers (Valsalva or cough), saline loading improved the detection rate from 17.4% to 32.0%. Overall, from amongst the 103 enrolled patients, saline bolusing resulted in a de novo diagnosis of PFO in 15 patients, atrial septal aneurysm in 15, PFO coexisting with an atrial septal aneurysm in 10, and pulmonary arteriovenous fistula in 5 patients. In conclusion, saline infusion in appropriately selected patients during transesophageal echocardiography significantly enhances the detection of PFOs and pulmonary arteriovenous fistulas.
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