C-reactive Protein and Risk of Right Ventricular Dysfunction and Mortality in Patients With Acute Symptomatic Pulmonary Embolism.

BACKGROUND: Right ventricle (RV) dysfunction increases the risk of death from pulmonary embolism (PE). C-reactive protein (CRP) might identify RV inflammation and dysfunction in patients with PE. METHODS: This cohort study enrolled consecutive stable patients with acute PE between 2017 and 2023. We stratified patients by quartiles of CRP. We evaluated the association between CRP quartiles and the presence of RV dysfunction, and used multivariable models to assess for an association between CRP and the outcomes of all-cause and PE-specific mortality during the 30 days of follow-up after PE diagnosis. RESULTS: The study included 633 stable patients with PE. Patients without RV dysfunction had significantly lower median (IQR) CRP levels compared with patients with RV dysfunction (n=509, 31.7 [10.0-76.4]mg/L vs n=124, 45.4 [16.0-111.4]mg/L; P=0.018). CRP showed a statistically significant positive association with the presence of RV dysfunction (P<0.01). On multivariable analysis, CRP level was not significantly associated with 30-day all-cause mortality (adjusted odds ratio [OR] per mg/L increment, 1.00; 95% CI, 1.00-1.01; P=0.095), but higher CRP was associated with significantly higher PE-related mortality (adjusted OR, 1.01; 95% CI, 1.00-1.01; P=0.026). Compared with patients in CRP quartile 1, patients in quartiles 2, 3, and 4 had a stepwise increase in the adjusted odds of 30-day all-cause death of 2.41 (P=0.148), 3.04 (P=0.062), and 3.15 (P=0.052), respectively. CONCLUSIONS: As an indicator of RV dysfunction, CRP may improve risk stratification algorithms for hemodynamically stable patients with acute symptomatic PE.

Occult cancer in patients with unprovoked venous thromboembolism: A nested case-control study.

OBJECTIVES: Detecting occult cancer in patients with unprovoked venous thromboembolism (VTE) remains a significant challenge. Our objective was to investigate the potential predictive role of coagulation-related biomarkers in the diagnosis of occult malignancies. METHODS: We conducted a nested case-control study with a 1-year prospective cohort of 214 patients with unprovoked VTE, with a focus on identifying occult cancer. At the time of VTE diagnosis, we measured various biomarkers, including soluble P-selectin (sP-selectin), dimerized plasmin fragment D (D-dimer), platelets, leukocytes, hemoglobin, total extracellular vesicles (EVs), EVs expressing tissue factor on their surface (TF+EVs), and EVs expressing P-selectin on their surface (Psel+EVs) in all participants. RESULTS: We observed statistically significant increased levels of sP-selectin (P = .015) in patients with occult cancer. Despite an increase in Psel+EVs, TF+EVs, D-dimer, and platelets within this group, however, no significant differences were found. When sP-selectin exceeded 62 ng/mL and D-dimer surpassed 10,000 µg/L, the diagnosis of occult cancer demonstrated a specificity of up to 91% (95% CI, 79.9%-96.7%). CONCLUSIONS: The combination of sP-selectin and D-dimer can be a valuable biomarker in detecting occult cancer in patients with unprovoked VTE. Further research is necessary to ascertain whether easily measurable biomarkers such as sP-selectin and D-dimer can effectively distinguish between patients who have VTE with and without hidden malignancies.

Improvement of thrombosis management in patients with cancer: a practical consensus document of recommendations for cancer-associated thrombosis patients' healthcare in Spain.

Cancer patients are at risk of venous thromboembolism (VTE), its recurrence, but also at risk of bleeding while anticoagulated. In addition, cancer therapies have been associated to increased VTE risk. Guidelines for VTE treatment in cancer patients recommend low molecular weight heparins (LMWH) or direct oral anticoagulants (DOAC) for the initial treatment, DOAC for VTE short-term treatment, and LMWH or DOAC for VTE long-term treatment. This consensus article arises from a collaboration between different Spanish experts on cancer-associated thrombosis. It aims to reach an agreement on a practical document of recommendations for action allowing the healthcare homogenization of cancer-associated thrombosis (CAT) patients in Spain considering not only what is known about VTE management in cancer patients but also what is done in Spanish hospitals in the clinical practice. The text summarizes the current knowledge and available evidence on the subject in Spain and provides a series of practical recommendations for CAT management and treatment algorithms to help clinicians to manage CAT over time.

Symptom-related screening programme for early detection of chronic thromboembolic pulmonary hypertension after acute pulmonary embolism: the SYSPPE study.

BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) is the most severe long-term complication of acute pulmonary embolism (PE). We aimed to evaluate the impact of a symptom screening programme to detect CTEPH in PE survivors. METHODS: This was a multicentre cohort study of patients diagnosed with acute symptomatic PE between January 2017 and December 2018 in 16 centres in Spain. Patients were contacted by phone 2 years after the index PE diagnosis. Those with dyspnoea corresponding to a New York Heart Association (NYHA)/WHO scale≥II, visited the outpatient clinic for echocardiography and further diagnostic tests including right heart catheterisation (RHC). The primary outcome was the new diagnosis of CTEPH confirmed by RHC. RESULTS: Out of 1077 patients with acute PE, 646 were included in the symptom screening. At 2 years, 21.8% (n=141) reported dyspnoea NYHA/WHO scale≥II. Before symptom screening protocol, five patients were diagnosed with CTEPH following routine care. In patients with NYHA/WHO scale≥II, after symptom screening protocol, the echocardiographic probability of pulmonary hypertension (PH) was low, intermediate and high in 76.6% (n=95), 21.8% (n=27) and 1.6% (n=2), respectively. After performing additional diagnostic test in the latter 2 groups, 12 additional CTEPH cases were confirmed. CONCLUSIONS: The implementation of this simple strategy based on symptom evaluation by phone diagnosed more than doubled the number of CTEPH cases. Dedicated follow-up algorithms for PE survivors help diagnosing CTEPH earlier. TRIAL REGISTRATION NUMBER: NCT03953560.

Pulmonary embolism: a practical approach to update risk stratification and treatment decisions based on the guidelines.

INTRODUCTION: Pulmonary embolism (PE) is a prevalent condition with a substantial morbi-mortality worldwide. Proper risk stratification of PE is essential for identifying the most suitable therapeutic strategy and the optimal care setting for the patient. This process entails evaluating various factors, including symptoms, comorbidities, and right heart dysfunction. AREAS COVERED: This review assesses the tools and methods utilized to identify and stratify individuals based on the probability of developing deterioration or death related to PE. Current guidelines divide PE into three groups: high-risk (previously termed massive) PE, intermediate-risk (sub-massive) PE, and low-risk PE. Various risk scores, such as the simplified pulmonary embolism severity index (sPESI), Bova score, and the FAST score (incorporating Heart-Fatty Acid binding protein [H-ABP], Syncope, Tachycardia), aid in identifying patients at higher risk. Additionally, the Hestia score is instrumental in pinpointing low-risk patients. EXPERT OPINION: Presently, there is a dearth of high-quality frameworks for the optimal management and treatment of PE patients at risk of hemodynamic collapse. A consortium of experts is in the process of formulating a new conceptual model for risk stratification, taking into account a comprehensive array of variables and outcomes to facilitate more individualized management of acute PE.

Epidemiology of Lung Cancer Mortality in Spain: Updated Information (1982-2021) and Predictions up to 2046.

BACKGROUND: Patterns of lung cancer (LC) mortality are important for planning health services and resource management. OBJECTIVES: We aimed to provide updated information (1982-2021) and project (LC) mortality rates in Spain (2022-2046). METHOD: We analysed data from the Spanish National Statistics Institute about mortality in LC (1982-2021), and we made predictions for the period 2022-2046. RESULTS: In 2021, a total of 22,413 people died of LC, and for the period 2042-2046, the projected annual average was 25,549 deaths. In males, age-standardised mortality rates (ASMR) (overall) after an initial period of increase (1982-1996, 2.2%) declined until 2021 (-1.4% per year), and this decline is expected to continue in the future (-1.9% per year during the period 2022-2046), although the projected decline is slightly higher (-2.0% during the period 2022-2046). In men, ASMR (all ages) after an initial period of increase (1982-1996, 2.2%) declined until 2021 (-1.4% per year), and this decline is expected to continue in the future during the period 2022-2046. In women, both the overall and truncated rates (35-64) increase during the period 1982-2021 (4.1% and 6.0% per year, respectively), and projected rates showed that both will decrease during the period 2022-2046, although more markedly in the truncated rates (-1.9% per year) than in the overall rates (-0.5% per year). CONCLUSIONS: Our projections show the magnitude of a steady upward trend in LC mortality among women in Spain that appears to be beginning to reverse from the current decade (similar to that observed for incidence).

COVID-19-associated venous thromboembolism: risk of recurrence and major bleeding.

Background: Complications under anticoagulant treatment in patients with COVID-19-associated venous thromboembolism (VTE) have not been consistently reported. Objectives: This study aimed to compare the 90-day rates of VTE recurrences and major bleeding in patients with COVID-19-associated VTE versus those with VTE without COVID-19. Methods: We used the RIETE registry to compare the 3-month outcomes in patients with COVID-19-associated VTE versus those with VTE without COVID-19. Results: The study included 1,747 patients with COVID-19-associated VTE and 8,711 with VTE without COVID-19. Patients with COVID-19-associated VTE were more likely to be hospitalized at baseline and to present with pulmonary embolism. During the first 90 days, 123 patients (1.17%) developed VTE recurrences, and 266 (2.54%) experienced major bleeding. Patients with COVID-19-associated VTE had a similar rate of VTE recurrences (0.9% vs 1.2%) but a higher rate of major bleeding (4.6% vs 2.1%; P < .001) than those without COVID-19. Multivariable analysis adjusted for competing risks showed that patients with COVID-19-associated VTE had an increased risk of major bleeding (subhazard ratio, 1.395; 95% confidence interval, 1.037-1.877). The 30-day mortality after major bleeding was 26.3% in patients with COVID-19-associated VTE and 17.7% in those without COVID-19. Conclusion: Patients with COVID-19-associated VTE had a 5-fold higher rate of major bleeding than VTE recurrences during the first 90 days of anticoagulation. In VTE patients without COVID-19, both rates were similar. These findings highlight the importance of carefully monitoring and optimizing anticoagulation in these patients.

Oxygen Therapy in Patients With Intermediate-Risk Acute Pulmonary Embolism: A Randomized Trial.

BACKGROUND: The effect of supplemental oxygen therapy in patients with intermediate-risk pulmonary embolism (PE) who do not have hypoxemia at baseline is uncertain. RESEARCH QUESTION: Does supplemental oxygen improve echocardiographic parameters in nonhypoxemic patients with intermediate-risk PE? STUDY DESIGN AND METHODS: This pilot trial randomly assigned nonhypoxemic patients with stable PE and echocardiographic right ventricle (RV) enlargement to receive anticoagulation plus supplemental oxygen for the first 48 h vs anticoagulation alone. The primary outcome was normal echocardiographic RV size 48 h after randomization. Secondary efficacy outcomes were the numerical change in the RV to left ventricle (LV) diameter ratio measured 48 h and 7 days after randomization with respect to the baseline ratio measured at inclusion. RESULTS: The study was stopped prematurely because of the COVID-19 pandemic after recruiting 70 patients (mean ± SD age, 67.3 ± 16.1 years; 36 female [51.4%]) with primary outcome data. Forty-eight h after randomization, normalization of the RV size occurred in 14 of the 33 patients (42.4%) assigned to oxygen and in eight of the 37 patients (21.6%) assigned to ambient air (P = .08). In the oxygen group, the mean RV to LV ratio was reduced from 1.28 ± 0.28 at baseline to 1.01 ± 0.16 at 48 h (P < .001); in the ambient air group, mean RV to LV ratios were 1.21 ± 0.18 at baseline and 1.08 ± 0.19 at 48 h (P < .01). At 90 days, one major bleeding event and one death (both in the ambient air group) had occurred. INTERPRETATION: In analyses limited by a small number of enrollees, compared with ambient air, supplemental oxygen did not significantly increase the proportion of patients with nonhypoxemic intermediate-risk PE whose RV to LV ratio normalized after 48 h of treatment. This pilot trial showed improvement in some ancillary efficacy outcomes and provides support for a definitive clinical outcomes trial. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT04003116; URL: www. CLINICALTRIALS: gov.

When should we involve interventional radiology in the management of acute pulmonary embolism?

Pulmonary embolism (PE) is a common disease associated with high morbidity and mortality. Currently, guidelines recommend systemic thrombolysis in patients with haemodynamic instability (high-risk PE) or patients with intermediate-high-risk PE with haemodynamic deterioration. Nevertheless, more than half of high-risk PE patients do not receive systemic thrombolysis due to a perceived increased risk of bleeding. In these cases, percutaneous catheter-directed therapy (CDT) or surgical embolectomy should be considered. CDT has emerged and appears to be an effective alternative in treating PE, with a hypothetical lower risk of bleeding than systemic thrombolysis, acting directly in the thrombus with a much lower dose of thrombolytic drug or even without thrombolytic therapy. CDT techniques include catheter-directed clot aspiration or fragmentation, mechanical embolectomy, local thrombolysis, and combined pharmaco-mechanical approaches. A few observational prospective studies have demonstrated that CDT improves right ventricular function with a low rate of haemorrhage. Nevertheless, the evidence from randomised controlled trials is scarce. Here we review different scenarios where CDT may be useful and trials ongoing in this field. These results may change the upcoming guidelines for management and treatment of PE, establishing CDT as a recommended treatment in patients with acute intermediate-high-risk PE.

The risk of recurrent venous thromboembolism after discontinuation of anticoagulant therapy in patients with cancer-associated thrombosis: a systematic review and meta-analysis.

Background: The optimal duration of anticoagulation in patients with active cancer and venous thromboembolism (VTE) is unknown. Current clinical guidelines advocate anticoagulant therapy for 3-6 months and to continue anticoagulant therapy for as long as the cancer is active. However, an adequate systematic review on the rate of recurrent VTE after discontinuation of anticoagulant therapy has not been performed. Methods: For this systemic review and meta-analysis, we searched Embase.com, Medline (Ovid), Web of Science, Cochrane Library, and Google Scholar, from database inception to February 16, 2023, for studies on anticoagulant therapy in patients with cancer and the recurrence of venous thromboembolism after discontinuation of this therapy. We included randomised controlled trials and cohort studies published in English that reported on patients who met the following: cancer and a first VTE, completed at least 3 months of anticoagulant therapy, were followed after discontinuation of anticoagulant therapy, and with symptomatic recurrent VTE as an outcome during follow-up. Study-level data were requested from study authors. The primary outcome was the rate of recurrent VTE after discontinuation of anticoagulant therapy. A Bayesian random-effects meta-analysis was used to estimate the rate of recurrent VTE per 100 person-years for the pooled studies at different time intervals after discontinuation of anticoagulation therapy. We also calculated the cumulative VTE recurrence rate at different time intervals. Forest plots were mapped and the results were summarized by the median and 95% credible interval (CIs). This study was registered with PROSPERO, CRD42021249060. Findings: Of 3856 studies identified in our search, 33 studies were identified for inclusion. After requesting study-level data, 14 studies involving 1922 patients with cancer-associated thrombosis were included. The pooled rate of recurrent VTE per 100 person-years after discontinuation of anticoagulant therapy was 14.6 events (95% credible interval 6.5-22.8) in the first three months, decreasing to 1.1 events (95% CI 0.3-2.1) in year 2-3, and 2.2 events (95% CI 0.0-4.4) in year 3-5 after discontinuation of anticoagulant therapy. The cumulative VTE recurrence rate was 28.3% (95% CI 15.6-39.6%) at 1 year; 31.1% (95% CI 16.5-43.8%) at 2 years; 31.9% (95% CI 16.8-45.0%) at 3 years; and 35.0% (95% CI 16.8-47.4%) at 5 years after discontinuation of anticoagulant therapy. Interpretation: This meta-analysis demonstrates a high rate of recurrent VTE over time after discontinuation of anticoagulant therapy in patients with cancer-associated thrombosis. Our results support the current clinical guidelines to continue anticoagulant therapy in patients with active cancer. Funding: Erasmus MC.

Risk factors for pulmonary embolism in lung cancer patients with lower limb deep venous thrombosis: a case-control study.

Background: There is growing evidence that misdiagnosis contributes to the high mortality rate in lung cancer patients complicated with pulmonary embolism (PE). This current study analyzed predictors of PE in lung cancer patients with lower extremity deep venous thrombosis (DVT) with the aim of personalizing the treatment and management of patients with PE. Methods: This retrospective case-control study included lung cancer patients with DVT at the emergency department of Shanghai Chest Hospital from January 2018 to December 2019. Patients were classified as having DVT with or without PE. The following characteristics were examined, including age, gender, smoking, hypertension, surgical trauma, hyperlipidemia, long-term bedridden status, calf swelling, coronary heart disease, chronic pulmonary disease, DVT location, DVT type, prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen, and D-dimer, and univariate and multivariate analyses were performed. Results: A total of 90 patients with lung cancer and DVT were analyzed, of whom 60% (54/90) had PE. Those variables independently associated to PE were hypertension [odds ratio (OR): 7.883, 95% confidence interval (CI): 2.038-30.495, P=0.003], long-term bedridden status (OR: 4.166, 95% CI: 1.236-14.044, P=0.021), and D-dimer levels (OR: 2.123, 95% CI: 1.476-3.053, P=0.000) were identified as independent risk factors for PE. The cut-off value of the receiver operating characteristic (ROC) curve for predicting PE by presented scoring system according to the risk factors was 1.5 and the area under the curve (AUC) was 0.84 (P<0.001). Conclusions: Hypertension, being bedridden for an extended period, and elevated serum D-dimer levels were independent risk factors of PE in lung cancer patients with lower extremity DVT. Novel strategies for patient management should be developed to decrease the risk of PE.

Prospective study to evaluate quality of life in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative rare disease characterized by symptoms and signs in the upper and lower motor neurons, leading to progressive neuro-degeneration and muscle atrophy. Our objective was to analyse the quality of life (QoL) in patients with ALS and compare with general population and with patients with cancer. Prospective study from consecutive ALS patients in one center. In order to assess quality of life, during the first visit three questionnaires were administered: Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R), Short Form-36 (SF-36) and EuroQoL 5D (EQ-5D). We compared SF-36 of ALS patients with a reference population (n = 9151), and we compared the EQ-5D index score of ALS patients versus patients with cancer in the same area and in the same period (2015-2018). Between June 2015 and September 2017, 23 were included. The mean age was 65.1 ± 12.6 years and 56.5% were women. Compared with the general population, patients with ALS showed lowest QoL (p < 0.05) in all the dimensions, with a very important impairment in physical function (median: 0; p25-75: 0-10) and physical role (median: 0; p25-75: 0-6.25). In EQ-5D questionnaire, patients with ALS presented an EQ-5D index score of 0.21 ± 0.39 (mean ± standard deviation) with a visual analog scale (VAS) score of 0.32 ± 0.24. Compared with an oncological population, patients with ALS had a worse EQ-5D index score both clinically and statistically (0.21 ± 0.39 vs. 0.77 ± 0.27; p < 0.05). We demonstrate a poorer quality of life in patients with ALS is poor, and clinically and statistically worse than in patients with cancer or general population. New studies need to evaluate the impact of strategies in this population to improve the quality of life.

Feasibility of a screening algorithm for chronic thromboembolic pulmonary hypertension: The OSIRIS study.

INTRODUCTION: Chronic thromboembolic pulmonary hypertension (CTEPH) is a long-term sequel to pulmonary embolism (PE) whose incidence varies according to different published studies. We have carried out this study to determine its incidence within 2 years after index pulmonary embolism and to study limitations to an early diagnosis. MATERIAL AND METHODS: OSIRIS is a multicentre, longitudinal cohort study. Patients were followed for 3, 6, 12, and 24 months after pulmonary embolism using a structured three-step algorithm. A physician-centered questionnaire at least one positive response in a screening proceeded to the second step, transthoracic echocardiography. The third step consisted of ventilation/perfusion lung scintigraphy and right heart catheterisation. A transthoracic echocardiography was performed in patients without positive response in the screening questionnaire after 2 years. CTEPH diagnosis required haemodynamic confirmation by right heart catheterisation and mismatched perfusion defects on lung scintigraphy. RESULTS: A total of 1191 patients were enrolled in 18 Spanish hospitals. Cumulative CTEPH incidence after 2-years PE was: 2.49 % (95 % CI: 1.68-3.56) and the incidence rate of CTEPH was 1.1 cases per 1000 person-months (95 % CI: 0.725; 1.60). The CTEPH algorithm presented a lack of adherence of 29 %; patient and physician preferences posed barriers to the triage algorithm The screening questionnaire, in patients who completed the follow-up, shows a specificity of 91.3 % (89.0-93.2 %) and negative predictive value of 99.4 % (98.4-99.8 %).. CONCLUSIONS: OSIRIS provides practiced clinical based data on the chronic thromboembolic pulmonary hypertension incidence and identified barriers to the implementation of a 3-step triage algorithm for its detection. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT03134898.

Comparison of long-term complications in cancer patients with incidental and acute symptomatic venous thromboembolism.

Background: Clinical practice guidelines recommend that patients with incidental venous thromboembolism (VTE) receive the same anticoagulant therapy as those with symptomatic VTE. We aimed to compare the rate of complications between cancer patients with incidental and symptomatic VTE through a long-term follow-up cohort. Methods: We performed a post hoc analysis of prospective studies of cancer patients with VTE between 2008 and 2019, with the primary outcome of rates of recurrent VTE and clinically relevant bleeding (CRB) in incidental and symptomatic VTE groups. Results: In total, 796 patients were included, of which 42.8% had incidental VTE. No significant differences were noted in the rate of recurrent VTE (0.4 per 100 patients/month vs. 0.5 per 100 patients/month; p = 0.313) and in the rate of CRB (0.6 per 100 patients/month vs. 0.5 per 100 patients/month; p = 0.128) between patients with incidental VTE and symptomatic VTE, respectively. At six-month follow-ups, the cumulative incidence of CRB was significantly higher in patients with incidental VTE than that in those with symptomatic VTE (7.9% vs. 4.4%, respectively; OR: 1.8; 95% CI: 1.01-3.2). Conclusion: Cancer patients with incidental VTE had similar rates of CRB and VTE recurrence in long-term follow-up compared with patients with symptomatic VTE. At six-month follow-ups, patients with incidental VTE had a higher cumulative incidence of CRB than those with symptomatic VTE.

Risk of recurrent cancer-associated thrombosis after discontinuation of anticoagulant therapy.

Background: Clinical guidelines suggest continuing anticoagulation therapy for >6 months for patients with active cancer and venous thromboembolism (VTE). However, data regarding the safety of its discontinuation are scarce. Objectives: To valuate the risk factors and the incidence of recurrent VTE 6 months after the discontinuation of anticoagulation therapy in patients with cancer-associated thrombosis (CAT). Methods: We performed a retrospective study on consecutive patients with CAT recruited between 2008 and 2019. The primary and secondary outcomes were recurrent VTE at 6 and 12 months, respectively. Sensitivity analyses were conducted to investigate the possible heterogeneity of these effects. Results: A total of 311 patients were included, among whom 33.4% had metastases and 30.8% were still receiving oncological treatment after 6 months of anticoagulant therapy. At 6 and 12 months, the incidences of recurrent VTE were 6.1% (95% CI, 3.5-9.4%) and 8.7% (95% CI, 5.8-12.4%), respectively. Recurrent VTE was more frequent in patients with metastases at 6 (sub-distribution hazard ratio [SHR] 3.83; 95% CI, 1.54-9.52) and 12 months (SHR 5; 95% CI, 2.2-11.5). Patients with incidental VTE had fewer recurrent events at 6 (SHR 0.3; 95% CI, 0.1-0.8) and 12 months (SHR 0.3; 95% CI, 0.1-0.6) after discontinuing the anticoagulant therapy. Conclusion: The incidence of recurrent VTE at 6 and 12 months following the discontinuation of anticoagulant therapy is higher in patients with CAT. Patients with metastases were at an increased risk of recurrent VTE, whereas patients with incidental VTE were at a lower risk.

Platelet RNA sequencing for cancer screening in patients with unprovoked venous thromboembolism: a prospective cohort study.

BACKGROUND: Platelet RNA sequencing has been shown to accurately detect cancer in previous studies. OBJECTIVES: To compare the diagnostic accuracy of platelet RNA sequencing with standard-of-care limited cancer screening in patients with unprovoked venous thromboembolism (VTE). METHODS: Patients aged ≥40 years with unprovoked VTE were recruited at 13 centers and followed for 12 months for cancer. Participants underwent standard-of-care limited cancer screening, and platelet RNA sequencing analysis was performed centrally at study end for cases and selected controls. Sensitivity and specificity were calculated, using the predefined primary positivity threshold of 0.54 for platelet RNA sequencing aiming at 86% test sensitivity, and an additional predefined threshold of 0.89 aiming at 99% test specificity. RESULTS: A total of 476 participants were enrolled, of whom 25 (5.3%) were diagnosed with cancer during 12-month follow-up. For each cancer patient, 3 cancer-free patients were randomly selected for the analysis. The sensitivity of limited screening was 72% (95% CI, 52-86) at a specificity of 91% (95% CI, 82-95). The area under the receiver operator characteristic for platelet RNA sequencing was 0.54 (95% CI, 0.41-0.66). At the primary positivity threshold, all patients had a positive test, for a sensitivity estimated at 100% (95% CI, 87-99) and a specificity of 8% (95% CI, 3.7-16.4). At the secondary threshold, sensitivity was 68% (95% CI, 48-83; p value compared with limited screening 0.71) at a specificity of 36% (95% CI, 26-47). CONCLUSION: Platelet RNA sequencing had poor diagnostic accuracy for detecting occult cancer in patients with unprovoked VTE with the current algorithm.