Optimizing Venous Stenting: Consensus Recommendations for Enhanced Management of Lower Extremity Deep Vein Thrombosis.

INTRODUCTION: Deep vein thrombosis (DVT) poses a complex challenge and often leads to postthrombotic syndrome (PTS), a debilitating complication. The emergence of venous stents offers a potential preventive avenue against this complication. This study aimed to provide consensus recommendations on the use of venous stent for DVT. MATERIALS AND METHODS: From June to July 2023, 20 internal medicine, angiology and vascular surgery, and vascular and interventional radiology experts were involved in the Delphi process. Thirty-one recommendations, categorized into three thematic areas, were rigorously evaluated: indications for stent use, stent selection and placement, and monitoring and prevention of complications. Agreement was evaluated using a Likert scale, with consensus defined as agreement by two-thirds of the participants. RESULTS: Consensus was reached for 23 (74.2%) of 31 recommendations. The agreement was centered on considerations, such as stent placement in specific acute DVT scenarios, emphasizing pivotal stent characteristics. However, there were divergences in the recommended stent length to prevent migration and stent characteristics based on iliocaval bifurcation morphology. Notably, there was no consensus on whether patients with DVT caused by a major transient risk factor need more than 3 months of anticoagulation therapy or whether aspirin should be added to anticoagulant treatment after venous stenting. CONCLUSIONS: These consensus recommendations offer practical insights into optimizing venous stent use to prevent PTS in DVT patients. Addressing the critical aspects of stent selection, placement, and postprocedural care, these recommendations contribute to clinical decision-making. The identified divergences underscore the importance of consensus and thus indicate the need for further investigation.

Clinical Presentation and Outcomes of Patients With Cancer-Associated Isolated Distal Deep Vein Thrombosis.

PURPOSE: Patients with isolated distal deep vein thrombosis (DVT) have lower rates of adverse outcomes (death, venous thromboembolism [VTE] recurrence or major bleeding) than those with proximal DVT. It is uncertain if such findings are also observed in patients with cancer. METHODS: Using data from the international Registro Informatizado de la Enfermedad TromboEmbolica venosa registry, we compared the risks of adverse outcomes at 90 days (adjusted odds ratio [aOR]; 95% CI) and 1 year (adjusted hazard ratio [aHR; 95% CI]) in 886 patients with cancer-associated distal DVT versus 5,196 patients with cancer-associated proximal DVT and 5,974 patients with non-cancer-associated distal DVT. RESULTS: More than 90% of patients in each group were treated with anticoagulants for at least 90 days. At 90 days, the adjusted risks of death, VTE recurrence, or major bleeding were lower in patients with non-cancer-associated distal DVT than in patients with cancer-associated distal DVT (reference): aOR = 0.16 (0.11-0.22), aOR = 0.34 (0.22-0.54), and aOR = 0.47 (0.27-0.80), respectively. The results were similar at 1-year follow-up: aHR = 0.12 (0.09-0.15), aHR = 0.39 (0.28-0.55), and aHR = 0.51 (0.32-0.82), respectively. Risks of death, VTE recurrence, and major bleeding were not statistically different between patients with cancer-associated proximal versus distal DVT, both at 90 days: aOR = 1.11 (0.91-1.36), aOR = 1.10 (0.76-1.62), and aOR = 1.18 (0.76-1.83), respectively, and 1 year: aHR = 1.01 (0.89-1.15), aHR = 1.02 (0.76-1.35), and aHR = 1.10 (0.76-1.61), respectively. However, more patients with cancer-associated proximal DVT, compared with cancer-associated distal DVT, developed fatal pulmonary embolism (PE) during follow-up: The risk difference was 0.40% (95% CI, 0.23 to 0.58). CONCLUSION: Cancer-associated distal DVT has serious and relatively comparable outcomes compared with cancer-associated proximal DVT. The lower risk of fatal PE from cancer-associated distal DVT needs further investigation.

Cancer-Associated Thrombosis: Trends in Clinical Features, Treatment, and Outcomes From 2001 to 2020.

Background: Despite advances in cancer and venous thromboembolism (VTE) management, the epidemiology of cancer-associated thrombosis management over time remains unclear. Objectives: We analyzed data from the RIETE (Registro Informatizado de la Enfermedad Trombo Embólica) registry spanning 2001 to 2020 to investigate temporal trends in clinical characteristics and treatments for cancer-associated thrombosis. Methods: Using multivariable survival regression, we examined temporal trends in risk-adjusted rates of symptomatic VTE recurrences, major bleeding, and death within 30 days after incident VTE. Results: Among the 17,271 patients with cancer-associated thrombosis, there was a progressive increase in patients presenting with pulmonary embolism (from 44% in 2001-2005 to 55% in 2016-2020; P < 0.001 for trend), lung (from 12.7% to 18.1%; P < 0.001) or pancreatic cancer (from 3.8% to 5.6%; P = 0.003), and utilization of immunotherapy (from 0% to 7.4%; P < 0.001). Conversely, there was a decline in patients with prostate cancer (from 11.7% to 6.6%; P < 0.001) or carcinoma of unknown origin (from 3.5% to 0.7%; P < 0.001). At the 30-day follow-up, a reduction was observed in the proportion of patients experiencing symptomatic VTE recurrences (from 3.1% to 1.1%; P < 0.001), major bleeding (from 3.1% to 2.2%; P = 0.004), and death (from 11.9% to 8.4%; P < 0.001). Multivariable analyses revealed a decreased risk over time for VTE recurrence (adjusted subdistribution HR [asHR]: 0.94 per year; 95% CI: 0.92-0.98), major bleeding (asHR: 0.98; 95% CI: 0.96-0.99), and death (aHR: 0.97; 95% CI: 0.96-0.98). Conclusions: In this multicenter study of cancer patients with VTE, there was a decline in thrombotic, hemorrhagic, and fatal events from 2001 to 2020. (Registro Informatizado de la Enfermedad Trombo Embólica [RIETE]; NCT02832245).

Cancer Histology and Natural History of Patients with Lung Cancer and Venous Thromboembolism.

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.

Clinical Presentation and Short- and Long-term Outcomes in Patients With Isolated Distal Deep Vein Thrombosis vs Proximal Deep Vein Thrombosis in the RIETE Registry.

Importance: Insufficient data exist about the clinical presentation, short-term, and long-term outcomes of patients with isolated distal deep vein thrombosis (IDDVT), that is, thrombosis in infrapopliteal veins without proximal extension or pulmonary embolism (PE). Objective: To determine the clinical characteristics, short-term, and 1-year outcomes in patients with IDDVT and to compare the outcomes in unadjusted and multivariable adjusted analyses with patients who had proximal DVT. Design, Setting, and Participants: This was a multicenter, international cohort study in participating sites of the Registro Informatizado Enfermedad Tromboembólica (RIETE) registry conducted from March 1, 2001, through February 28, 2021. Patients included in this study had IDDVT. Patients with proximal DVT were identified for comparison. Patients were excluded if they had a history of asymptomatic DVT, upper-extremity DVT, coexisting PE, or COVID-19 infection. Main Outcomes and Measures: Primary outcomes were 90-day and 1-year mortality, 1-year major bleeding, and 1-year venous thromboembolism (VTE) deterioration, which was defined as subsequent development of proximal DVT or PE. Results: A total of 33 897 patients were identified with isolated DVT (without concomitant PE); 5938 (17.5%) had IDDVT (mean [SD] age, 61 [17] years; 2975 male patients [50.1%]), and 27 959 (82.5%) had proximal DVT (mean [SD] age, 65 [18] years; 14 315 male patients [51.2%]). Compared with individuals with proximal DVT, those with IDDVT had a lower comorbidity burden but were more likely to have had recent surgery or to have received hormonal therapy. Patients with IDDVT had lower risk of 90-day mortality compared with those with proximal DVT (odds ratio [OR], 0.47; 95% CI, 0.40-0.55). Findings were similar in 1-year unadjusted analyses (hazard ratio [HR], 0.52; 95% CI, 0.46-0.59) and adjusted analyses (HR, 0.72; 95% CI, 0.64-0.82). Patients with IDDVT had a lower 1-year hazard of VTE deterioration (HR, 0.83; 95% CI, 0.69-0.99). In 1-year adjusted analyses of patients without an adverse event within the first 3 months, IDDVT was associated with lower risk of VTE deterioration (adjusted HR, 0.48; 95% CI, 0.24-0.97). By 1-year follow-up, symptoms or signs of postthrombotic syndrome were less common in patients with IDDVT (47.6% vs 60.5%). Conclusions and Relevance: Results of this cohort study suggest that patients with IDDVT had a less ominous prognosis compared with patients with proximal DVT. Such differences were likely multifactorial, including the differences in demographics, risk factors, comorbidities, particularly for all-cause mortality, and a potential association of thrombus location with VTE deterioration and postthrombotic syndrome. Randomized clinical trials are needed to assess the optimal long-term management of IDDVT.

Enoxaparin versus dalteparin or tinzaparin in patients with cancer and venous thromboembolism: The RIETECAT study.

Background: Venous thromboembolism (VTE) is a frequent complication in patients with cancer and a leading cause of morbidity and death. Objectives: The objective of the RIETECAT study was to compare the long-term effectiveness and safety of enoxaparin versus dalteparin or tinzaparin for the secondary prevention of VTE in adults with active cancer. Methods: We used the data from the multicenter, multinational RIETE registry to compare the rates of VTE recurrences, major bleeding, or death over 6 months in patients with active cancer and acute VTE using full doses of enoxaparin versus dalteparin or tinzaparin, and a multivariable Cox proportional hazard model was used to analyze the primary end point. Results: From January 2009 to June 2018, 4451 patients with active cancer received full doses of the study drugs: enoxaparin, 3526 patients; and dalteparin or tinzaparin, 925 (754 + 171) patients. There was limited difference in VTE recurrences (2.0% vs 2.5%) and mortality rate (19% vs 17%) between the enoxaparin and dalteparin or tinzaparin subgroups. However, there was a slight numerical increase in major bleeding (3.1% vs 1.9%). Propensity score matching confirmed that there were no differences in the risk for VTE recurrences (adjusted hazard ratio [aHR], 0.81; 95% confidence interval [CI], 0.48-1.38), major bleeding (aHR, 1.40; 95% CI, 0.80-2.46), or death (aHR, 1.07; 95% CI, 0.88-1.30) between subgroups. Conclusions: In RIETECAT, in patients with cancer and VTE receiving full-dose enoxaparin or dalteparin or tinzaparin, no statistically significant differences were observed regarding effectiveness and safety outcomes over a 6-month period.

Outcome of Cancer-Associated Venous Thromboembolism Is More Favorable among Patients with Hematologic Malignancies than in Those with Solid Tumors.

BACKGROUND: The natural history of patients with hematologic cancer and venous thromboembolism (VTE) has not been consistently evaluated. We aimed to compare the rates of symptomatic recurrent VTE, major bleeding, or death during anticoagulant therapy in patients with VTE associated with hematologic versus solid cancers. METHODS: Consecutive patients with active cancer recruited in RIETE were evaluated. Their baseline characteristics, treatments, and outcomes during the course of anticoagulation were compared. Univariate and multivariate competing-risk analyses were performed. RESULTS: As of December 2020, 16,694 patients with cancer and VTE were recruited. Of these, 1,062 (6.4%) had hematologic cancers. Hematologic patients were less likely to initially present with pulmonary embolism (46 vs. 55%) and more likely with upper extremity deep vein thrombosis (25 vs. 18%). They also were more likely to have severe thrombocytopenia at baseline (5.6 vs. 0.7%) or to receive chemotherapy (67 vs. 41%). During the course of anticoagulation (median, 150 vs. 127 days), 1,071 patients (6.4%) developed VTE recurrences, 806 (4.8%) suffered major bleeding, and 4,136 (24.8%) died. Patients with hematologic cancers had lower rates of recurrent VTE (rate ratio [RR]: 0.73; 95% confidence interval [CI]: 0.56-0.95), major bleeding (RR: 0.72; 95% CI: 0.53-0.98), or all-cause death (RR: 0.49; 95% CI: 0.41-0.57) than those with solid cancers. Patients with multiple myeloma showed the best outcomes. CONCLUSION: Patients with hematologic cancers, particularly multiple myeloma, and VTE had better outcomes than those with solid cancers. These findings are relevant for the interpretation of previous clinical trials and the design of future studies.

Global Methylome Scores Correlate with Histological Subtypes of Colorectal Carcinoma and Show Different Associations with Common Clinical and Molecular Features.

BACKGROUND: The typical methylation patterns associated with cancer are hypermethylation at gene promoters and global genome hypomethylation. Aberrant CpG island hypermethylation at promoter regions and global genome hypomethylation have not been associated with histological colorectal carcinomas (CRC) subsets. Using Illumina's 450 k Infinium Human Methylation beadchip, the methylome of 82 CRCs were analyzed, comprising different histological subtypes: 40 serrated adenocarcinomas (SAC), 32 conventional carcinomas (CC) and 10 CRCs showing histological and molecular features of microsatellite instability (hmMSI-H), and, additionally, 35 normal adjacent mucosae. Scores reflecting the overall methylation at 250 bp, 1 kb and 2 kb from the transcription starting site (TSS) were studied. RESULTS: SAC has an intermediate methylation pattern between CC and hmMSI-H for the three genome locations. In addition, the shift from promoter hypermethylation to genomic hypomethylation occurs at a small sequence between 250 bp and 1 Kb from the gene TSS, and an asymmetric distribution of methylation was observed between both sides of the CpG islands (N vs. S shores). CONCLUSION: These findings show that different histological subtypes of CRC have a particular global methylation pattern depending on sequence distance to TSS and highlight the so far underestimated importance of CpGs aberrantly hypomethylated in the clinical phenotype of CRCs.

Rivaroxaban or apixaban in fragile patients with acute venous thromboembolism.

INTRODUCTION: The efficacy and safety of the direct oral anticoagulants (DOACs) in fragile patients (age ≥ 75 years and/or creatinine clearance [CrCl] levels ≤50 mL/min and/or body weight ≤50kg) with venous thromboembolism (VTE) have not been consistently compared. MATERIAL AND METHODS: We used the RIETE database to compare the rates of the composite of VTE recurrences or major bleeding during anticoagulation in fragile patients with VTE, according to the use of rivaroxaban or apixaban for initial and long-term therapy. RESULTS: From January 2013 to October 2019, 36,889 patients were recruited, of whom 14,831 (40%) were fragile. Overall, 999 fragile patients (15%) received DOACs starting within the first 48 h: rivaroxaban 711 and apixaban 288. Median duration of therapy was: 113 vs. 111 days. A substantial amount of patients in both subgroups (25% vs. 40%) received non-recommended doses of DOACs. During anticoagulation, 13 patients developed VTE recurrences, 18 had major bleeding and 36 died. When only considering patients receiving recommended doses (n = 705), there were no differences between drugs in the rate of the composite outcome (rate ratio [RR]: 1.08; 95%CI: 0.35-3.30) or all-cause death (RR: 0.99; 95%CI: 0.32-3.08). On multivariable analysis, patients receiving rivaroxaban or apixaban at recommended doses had a similar risk for the composite outcome (hazard ratio: 1.34; 95%CI: 0.35-5.06). CONCLUSION: The use of rivaroxaban or apixaban at recommended doses in fragile patients with VTE was associated with a similar risk for VTE recurrences or major bleeding.

Management and outcomes of cancer patients with venous thromboembolism presenting with thrombocytopenia.

INTRODUCTION: Treatment of venous thromboembolism (VTE) in cancer patients with thrombocytopenia is challenging due to perceived higher risk of bleeding. MATERIAL AND METHODS: We used the RIETE registry to compare the 10- and 30-day outcomes in cancer patients with acute VTE, according to platelet count at baseline. RESULTS: As of December 2018, 15,337 cancer patients with VTE were included: 166 (1.1%) had <50 × 109 platelets/L (severe thrombocytopenia), 711 (4.6%) had 50-99 × 109/L (mild thrombocytopenia) and 14,460 (94.3%) had ≥100 × 109/L (normal count). Most patients in all subgroups received initial therapy with low-molecular-weight heparin (LMWH), but 62% of those with severe thrombocytopenia received <150 IU/kg/day LMWH, 42% received <100 IU/kg/day. The mortality rate progressively decreased with increasing platelet counts (12%, 9.4% and 3.3% respectively at 10 days, 27%, 18% and 9.4% at 30 days), but the major bleeding rates did not (1.2%, 2.5% and 1.3% respectively at 10 days, 2.4%, 4.4% and 2.2% at 30 days). On multivariable analysis, patients with severe thrombocytopenia had a similar risk for major bleeding at 10 days (OR 0.84; 95%CI 0.20-3.49) and at 30 days (OR 0.90; 95%CI 0.32-2.49), but those with mild thrombocytopenia were at increased risk both at 10 days (OR 2.11; 95%CI 1.27-3.49) and at 30 days (OR 1.91; 95%CI 1.29-2.84). CONCLUSIONS: Cancer patients with acute VTE and baseline thrombocytopenia often receive initial lower-than recommended doses of LMWH. Although caution is required, this practice seems to be safe in patients with severe thrombocytopenia. Nonetheless, there was an inverse correlation between baseline platelet count and mortality.

Prediction of early mortality in patients with cancer-associated thrombosis in the RIETE Database.

BACKGROUND: Proper risk stratification of patients for early mortality after cancer-associated thrombosis may lead to personalized anticoagulation protocols. Therefore, we aimed to derive and validate a scoring system to predict early mortality in this population. To this end, we selected patients with active cancer and thrombosis from the Computerized Registry of Patients with Venous Thromboembolism database. METHODS: The main outcome was all cause mortality within the month following a thrombotic event. We used a simple random selection to split are data in a derivation and a validation cohort. In the derivation cohort, we used recursive partitioning and binary logistic regression to identify groups at risk and to determine the likelihood of the primary outcome. The risk score was developed based on odds ratios from the final multivariate model, and then tested in the validation cohort. RESULTS: In 10,025 eligible patients, we identified 6 predictors of 30-day mortality: leukocytosis ≥11.5x109/L; platelet count ≤160x109/L, metastasis, recent immobility, initial presentation as pulmonary embolism and Body Mass Index <18.5. The model divided the population into 3 risk categories: low (score 0-3), moderate (score 4-6), and high (score ≥7). The AUC for the overall score was 0.74, and using a cutoff ≥7 points, the model had a negative predictive value of 94.4%, a positive predictive value of 23.1%, a sensitivity of 73.3%, and a specificity of 64.6% in the validation cohort. CONCLUSIONS: Our validated risk model may assist physicians in the selection of patients for outpatient management, and perhaps anticoagulant, considering expanding anticoagulation options.

Arterial Ischemic Events Are a Major Complication in Cancer Patients with Venous Thromboembolism.

BACKGROUND: Venous thromboembolism is common in patients with malignancies, affecting up to 10% of this patient population. The association between arterial ischemic events and venous thromboembolism also has been established. However, the influence of arterial ischemic events on outcomes in cancer patients with venous thromboembolism has not been fully determined. METHODS: The current study analyzed clinical characteristics, time course, risk factors, incidence and severity of venous thromboembolism recurrences, arterial ischemic events and major bleeding in 5717 patients with active cancer and venous thromboembolism recruited into RIETE (multi-center prospective registry of patients with objectively confirmed venous thromboembolism). RESULTS: During the anticoagulation course (median 7.3 months), 499 (8.7%) patients developed venous thromboembolism recurrences, 63 (1.1%) developed arterial events, and 346 (6.1%) suffered from major bleeding. Overall, major bleeding and arterial events appeared earlier (median 35 and 36 days, respectively) than venous thromboembolism recurrences (median 97 days). Thirty-day mortality rates after each event were: 20% after recurrent pulmonary embolism, 13% after recurrent deep vein thrombosis, 41% after major bleeding, 40% after myocardial infarction, 64% after ischemic stroke, and 83% after lower limb amputation. Bleeding was the leading cause of death (67 fatal bleeds), whereas cumulative mortality due to arterial ischemic events (n = 27) was similar to that related to pulmonary embolism recurrences (n = 26). CONCLUSIONS: In this study, arterial ischemic events and major bleeding appeared early after venous thromboembolism in patients with active cancer and were among frequent causes of their deaths. The risk and severity of arterial events need to be considered in this clinical setting.

Anticoagulant therapy for venous thromboembolism in patients with inflammatory bowel disease.

BACKGROUND: There is lack of evidence to guide the type, intensity, and the duration of anticoagulation following venous thromboembolism (VTE) in patients with inflammatory bowel disease (IBD). PATIENTS AND METHODS: Registro Informatizado Enfermedad Trombo Embólica (RIETE) is an ongoing, multicenter, observational registry of consecutive patients with symptomatic, objectively confirmed, acute VTE. We used the RIETE database to compare the rate of VTE recurrences and major bleeding during the course of anticoagulation in noncancer patients with or without IBD. RESULTS: As of October 2014, 41 927 patients without active cancer have been recruited in RIETE. Of these, 265 (0.63%) had IBD and 85 (32%) had the VTE during an acute flare. The duration of anticoagulation was similar in patients with VTE during an acute flare (8.3±8.8 months), in remission (9.4±11.5 months), or without IBD (10.0±12.8 months). The rate of VTE recurrences [7.25, 95% confidence interval (CI): 1.46-21.2; 8.84, 95% CI: 3.23-19.2; and 5.85, 95% CI: 5.46-6.26 per 100 patient-years, respectively] and major bleeding (7.25, 95% CI: 1.46-21.2; 2.95, 95% CI: 0.33-10.6; and 4.79, 95% CI: 4.44-5.15, respectively) were similar in all three subgroups. Propensity score matching analysis confirmed the absence of differences in the rate of VTE recurrences (rate ratio: 1.16, 95% CI: 0.54-2.47) or major bleeding (rate ratio: 0.84, 95% CI: 0.31-2.23) between patients with or without IBD. CONCLUSION: Therapeutic anticoagulation for patients with IBD and VTE is as safe and effective as for those with VTE without IBD.

Clinical Characteristics and Outcomes of Patients with Lung Cancer and Venous Thromboembolism.

Background The natural history of patients with lung cancer and venous thromboembolism (VTE) has not been consistently evaluated. Methods We used the RIETE (Registro Informatizado Enfermedad TromboEmbólica) database to assess the clinical characteristics, time course, and outcomes during anticoagulation of lung cancer patients with acute, symptomatic VTE. Results As of May 2017, a total of 1,725 patients were recruited: 1,208 (70%) presented with pulmonary embolism (PE) and 517 with deep vein thrombosis (DVT). Overall, 865 patients (50%) were diagnosed with cancer <3 months before, 1,270 (74%) had metastases, and 1,250 (72%) had no additional risk factors for VTE. During anticoagulation (median, 93 days), 166 patients had symptomatic VTE recurrences (recurrent DVT: 86, PE: 80), 63 had major bleeding (intracranial 11), and 870 died. The recurrence rate was twofold higher than the major bleeding rate during the first month, and over threefold higher beyond the first month. Fifty-seven patients died of PE and 15 died of bleeding. Most fatal PEs (84%) and most fatal bleeds (67%) occurred within the first month of therapy. Nine patients with fatal PE (16%) died within the first 24 hours. Of 72 patients dying of PE or bleeding, 15 (21%) had no metastases and 29 (40%) had the VTE shortly after surgery or immobility. Conclusion Active surveillance on early signs and/or symptoms of VTE in patients with recently diagnosed lung cancer and prescription of prophylaxis in those undergoing surgery or during periods of immobilization might likely help prevent VTE better, detect it earlier, and treat it more efficiently.

Cancer-Associated Thrombosis: Beyond Clinical Practice Guidelines-A Multidisciplinary (SEMI-SEOM-SETH) Expert Consensus.

Despite the growing interest and improved knowledge about venous thromboembolism in cancer patients in the last years, there are still many unsolved issues. Due to the limitations of the available literature, evidence-based clinical practice guidelines are not able to give solid recommendations for challenging scenarios often present in the setting of cancer-associated thrombosis (CAT). A multidisciplinary expert panel from three scientific societies-Spanish Society of Internal Medicine (SEMI), Spanish Society of Medical Oncology (SEOM), and Spanish Society Thrombosis and Haemostasis (SETH)-agreed on 12 controversial questions regarding prevention and management of CAT, which were thoroughly reviewed to provide further guidance. The suggestions presented herein may facilitate clinical decisions in specific complex circumstances, until these can be made leaning on reliable scientific evidence.

Gender differences in patients with venous thromboembolism and five common sites of cancer.

BACKGROUND: The outcome of cancer patients with venous thromboembolism (VTE) may differ according to gender. METHODS: We used the RIETE database to compare the rate of VTE recurrences, major bleeding and mortality in patients with lung, colorectal, pancreatic, hematologic or gastric cancer during the course of anticoagulation, according to gender. RESULTS: As of January 2016, 11,055 patients with active cancer were enrolled: 1,727 had lung cancer, 1,592 colorectal, 840 hematologic, 517 pancreatic and 459 had gastric cancer. Compared with men (N = 3,130), women (N = 2,005) were more likely to have colorectal, pancreatic or hematologic cancer, and less likely to have lung cancer. Most patients (91%) were initially treated with low-molecular-weight heparin (LMWH), but women received higher daily doses per body weight. Then, 66% kept receiving LMWH for long-term therapy. During the course of anticoagulation, 302 patients developed recurrent VTE, 220 bled and 1,749 died. Compared with men, women had a similar rate of VTE recurrences or major bleeding, and a lower mortality (risk ratio [RR]: 0.90; 95% CI: 0.82-0.99). When separately comparing outcomes according to cancer site, women with lung cancer had a lower mortality (RR: 0.79; 95% CI: 0.70-0.92), those with colorectal cancer had a higher mortality (RR: 1.25; 95% CI: 1.02-1.54) and those with gastric cancer had a higher rate of VTE recurrences than men (RR: 2.47; 95% CI: 1.04-5.89). CONCLUSIONS: VTE women with lung, colorectal, pancreatic, haematological or gastric cancer experienced a similar outcome during the course of anticoagulant therapy than men with similar cancers.

Outcome after discontinuing anticoagulant therapy in women with venous thromboembolism during hormonal use.

INTRODUCTION: Whether women developing venous thromboembolism (VTE) while using hormonal therapy should be classified as having "unprovoked" or "provoked" VTE is controversial. METHODS: We used the RIETE (Registro Informatizado Enfermedad TromboEmbólica) database to compare the rate of symptomatic VTE recurrences after discontinuing anticoagulation in 3 subgroups of women aged ≤50years without cancer, pregnancy or puerperium: (1) those with hormonal therapy and no additional risk factors (hormonal users only); (2) those with unprovoked VTE; and (3) those with additional risk factors, with or without hormonal therapy. RESULTS: As of March 2016, 1513 women had been followed-up for at least one month after discontinuing anticoagulation. Of these, 654 (43%) were hormonal users only, 390 (26%) had unprovoked VTE and 469 (31%) had transient risk factors with or without hormonal therapy. After discontinuing anticoagulation, the rate of VTE recurrences in women with hormonal use only (2.44 per 100 patient-years; 95% CI: 1.53-3.69) was significantly lower than in those with unprovoked VTE (6.03; 95% CI: 3.97-8.77) and similar to those with transient risk factors (2.58; 95% CI: 1.50-4.13). Interestingly, the rate of VTE recurrences presenting as pulmonary embolism in women with hormonal use only (0.55 per 100 patient-years; 95% CI: 0.18-1.29) was similar to those with transient risk factors (0.46; 95% CI: 0.09-1.33) and 4-fold lower than in women with unprovoked VTE (2.23; 95% CI: 1.07-4.10). CONCLUSIONS: After discontinuing anticoagulation, the rate of VTE recurrences in hormonal users only was significantly lower than in women with unprovoked VTE and similar to the rate in women with additional risk factors.

Predictors of active cancer thromboembolic outcomes. RIETE experience of the Khorana score in cancer-associated thrombosis.

Even though the Khorana risk score (KRS) has been validated to predict against the development of VTE among patients with cancer, it has a low positive predictive value. It is also unknown whether the score predicts outcomes in patients with cancer with established VTE. We selected a cohort of patients with active cancer from the RIETE (Registro Informatizado Enfermedad TromboEmbolica) registry to assess the prognostic value of the KRS at inception in predicting the likelihood of VTE recurrences, major bleeding and mortality during the course of anticoagulant therapy. We analysed 7948 consecutive patients with cancer-associated VTE. Of these, 2253 (28 %) scored 0 points, 4550 (57 %) 1-2 points and 1145 (14 %) scored ≥3 points. During the course of anticoagulation, amongst patient with low, moderate and high risk KRS, the rate of VTE recurrences was of 6.21 (95 %CI: 4.99-7.63), 11.2 (95 %CI: 9.91-12.7) and 19.4 (95 %CI: 15.4-24.1) events per 100 patient-years; the rate of major bleeding of 5.24 (95 %CI: 4.13-6.56), 10.3 (95 %CI: 9.02-11.7) and 19.4 (95 %CI: 15.4-24.1) bleeds per 100 patient-years and the mortality rate of 25.3 (95 %CI: 22.8-28.0), 58.5 (95 %CI: 55.5-61.7) and 120 (95 %CI: 110-131) deaths per 100 patient-years, respectively. The C-statistic was 0.53 (0.50-0.56) for recurrent VTE, 0.56 (95 %CI: 0.54-0.59) for major bleeding and 0.54 (95 %CI: 0.52-0.56) for death. In conclusion, most VTEs occur in patients with low or moderate risk scores. The KRS did not accurately predict VTE recurrence, major bleeding, or mortality among patients with cancer-associated thrombosis.

Analysis of clinical factors affecting the rates of fatal pulmonary embolism and bleeding in cancer patients with venous thromboembolism.

BACKGROUND: In cancer patients with symptomatic venous thromboembolism (VTE) (deep-vein thrombosis (DVT) and/or pulmonary embolism (PE)), clinical factors that influence the benefit-risk balance of anticoagulation need to be identified so treatment intensity and duration can be optimally adjusted for the individual patient. METHODS: Using clinical data for cancer patients with VTE obtained from the RIETE registry, we compared how rates of fatal PE and fatal bleeding during and after anticoagulation vary depending on patients' clinical characteristics. RESULTS: Data were analysed from the 10,962 cancer patients with VTE (5,740 with PE with or without DVT; 5,222 with DVT alone) in RIETE registry as of March 2016. Fatal PE occurred in 2.18% of patients, while fatal bleedings occurred in 1.55%. During the 12 months from initial VTE, fatal PE was the most common cause of death, after disseminating cancer, and bleeding the fourth most common. In patients initially presenting with PE, fatal PE during anticoagulation was 4-fold more frequent than fatal bleeding (204 vs 51 deaths) and occurred mostly during the first month of treatment (196/223, 88%). In patients initially presenting with DVT, fatal PE was 3-fold lower than fatal bleeding during (25 vs 85 deaths) and after anticoagulation treatment (8 vs 37 deaths). During the 12-month follow-up, other characteristics of cancer patients with VTE were identified as more common in fatal cases of PE and/or bleeding than in surviving cases. INTERPRETATION: Baseline clinical characteristics may determine anticoagulation outcomes in cancer patients with VTE and should be further investigated as possible factors for guiding changes in current practices of anticoagulation, such as adjusting anticoagulation intensity and duration in selected patients.