BACKGROUND AND AIMS:Patients with cancer and venous thromboembolism (VTE) have a high risk of recurrent VTE and anticoagulant-related bleeding. This study aimed to identify prognostic factors for these complications. METHODS:A systematic review was performed for randomized trials and cohort studies evaluating prognostic factors for recurrent VTE or anticoagulant-related bleeding in adult patients with cancer and VTE. Adjusted hazard ratios (aHRs) for factors were pooled using random-effects meta-analysis. The certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation approach. RESULTS:Thirty-three studies (n = 96 753) were included in the meta-analyses. Factors with high certainty of association with increased risk of recurrent VTE included a previous history of VTE [aHR 1.50 (95% CI 1.08-2.09)], Eastern Cooperative Oncology Group (ECOG) performance status >0 [1.81 (1.34-2.46)] or >1 [2.44 (1.55-3.84)], advanced cancer [1.38 (1.15-1.65)], and specific cancer sites including lung [1.78 (1.29-2.46)], hepatobiliary [2.37 (1.70-3.30)], pancreas [3.20 (2.06-4.96)], and genitourinary [1.38 (1.14-1.67)]. Conversely, recent surgery [aHR 0.56 (95% CI 0.40-0.76)] and breast cancer [0.43 (0.23-0.81)] had a high certainty of association with a decreased risk. Factors with a high certainty of association with an increased risk of anticoagulant-related bleeding included a history of bleeding [aHR 2.41 (95% CI 1.50-3.88)], ECOG performance status ≥2 [2.10 (1.48-2.99)], advanced cancer [1.60 (1.29-1.97)], and cancers of the brain [2.25 (1.64-3.09)], gastrointestinal system [1.74 (1.44-2.11)], genitourinary system [1.90 (1.48-2.45)], and prostate [1.72 (1.26-2.34)]. CONCLUSIONS:The prognostic factors identified in this meta-analysis should be considered as part of risk stratification frameworks for anticoagulation management in patients with cancer and VTE.

BACKGROUND AND AIMS:Patients with cancer have increased risk of venous thromboembolism (VTE) and bleeding. Inflammatory and cardiac biomarkers may predict these complications, but their role remains unclear. This study examined associations between two inflammatory-related markers (C-reactive protein and growth differentiation factor-15) and two cardiac markers [N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin T (hs-TnT)] with VTE and clinically relevant bleeding in cancer patients. METHODS:A post hoc analysis of the AVERT trial, which evaluated apixaban for VTE prevention in ambulatory cancer patients with a Khorana score of ≥2, was performed. Biomarkers were measured at baseline and 1 month, with C-reactive protein also at 3 months. Fine and Gray regression, accounting for competing risk of death and adjusted for age and advanced cancer, estimated subdistribution hazard ratios (SHRs) for VTE and clinically relevant bleeding. RESULTS:Of 574 patients, 514 provided baseline samples. One- and 3-month samples were available from 454 and 447, and 378 and 364, patients without prior VTE and bleeding events, respectively. Elevated baseline growth differentiation factor-15 was associated with increased VTE risk [SHR 1.36, 95% confidence interval (CI) 1.01-1.84]. N-terminal pro-B-type natriuretic peptide (SHR 1.44, 95% CI 1.08-1.92) and C-reactive protein (SHR 1.38, 95% CI 1.07-1.76) were linked to bleeding risk. Increasing high-sensitivity troponin T from baseline to 1 month was associated with higher VTE risk (SHR 1.89, 95% CI 1.14-3.16). Nomograms were developed to estimate VTE and clinically relevant bleeding risks. CONCLUSIONS:Select inflammatory-related and cardiac markers were associated with VTE and bleeding risks in cancer patients, which can be determined using developed nomograms. Prospective research is needed to confirm these findings.

BACKGROUND:Patients with cancer are at elevated risk of venous thromboembolism (VTE). While primary thromboprophylaxis reduces VTE incidence, it also increases bleeding risk, necessitating accurate risk stratification. Existing tools (eg, the Khorana score) have modest predictive value, and bleeding risk models have not been validated in ambulatory patients with cancer. OBJECTIVES:To develop and internally validate prediction models for VTE and clinically relevant bleeding in ambulatory patients with cancer initiating chemotherapy. METHODS:We used data from 514 participants in the apixaban for the prevention of venous thromboembolism in high-risk ambulatory cancer patients randomized trial. Outcomes included objectively confirmed VTE and clinically relevant bleeding over 7 months. For each outcome, we trained 3 models: logistic regression with L1 regularization and 2 extreme gradient boosting models (1 using all variables, including biomarkers and genetic data; 1 using only routinely collected variables). Performance was evaluated using optimism-adjusted area under the curve (AUC) values, precision-recall AUC values, calibration, and diagnostic statistics. RESULTS:VTE and clinically relevant bleeding occurred in 8.4% and 9.0% of patients, respectively. The full-variable extreme gradient boosting model performed best (VTE AUC: 0.92; bleeding AUC: 0.90). Key VTE predictors included factor V Leiden, topoisomerase inhibitor use, apixaban, stomach or pancreatic cancer, hemoglobin and high-sensitivity troponin T whereas top bleeding predictors included extracellular vesicles procoagulant activity, N-terminal pro-B-type natriuretic peptide, C-reactive protein, age, body mass index, and blood counts. CONCLUSION:In this proof-of-concept study, prediction models incorporating biomarker and genetic variables accurately predicted VTE and clinically relevant bleeding in patients with cancer, though caution is warranted due to the modest sample size.

Cancer is associated with a substantially elevated risk of venous thromboembolism (VTE), but this risk varies considerably between individuals depending on several clinical and laboratory variables. Biomarkers predictive of VTE are needed to better stratify risk. We had previously identified candidate biomarkers predictive of cancer-associated VTE in a substudy of CASSINI, a randomized trial of thromboprophylaxis in people with cancer with Khorana score (KS) of > 2. In this study, we evaluated these biomarkers for prediction of VTE or death in plasma specimens derived from patients enrolled in AVERT, a similarly designed trial of thromboprophylaxis. We used available baseline plasma samples from 498 of 574 individuals enrolled in AVERT, a prospective randomized trial of apixaban prophylaxis in cancer with KS > 2. Levels of 9 proteins - C-reactive protein (CRP), chemokine ligand 13 (CCL13/MCP-4), N-terminal prohormone of brain natriuretic peptide (NT-proBNP), human growth hormone (hGH), high sensitivity troponin T (hsTnT), C X C motif chemokine 12 (CXCL12/SDF-1), interleukin 1 receptor (IL1R1), thyroid stimulating hormone (TSH), and growth differentiation factor 15 (GDF-15) – were assessed for association with VTE, death, and VTE or death outcomes. Protein concentrations were log₂ transformed and analyzed using cause specific multivariate Cox proportional hazards models adjusted for age, sex, study arm, and Khorana VTE risk score with baseline hazards dependent on cancer type. The study population comprised 498 patients, evenly split between apixaban and placebo arms. Median age at enrollment was 68 years; 58% were female and 93% were White. The most common cancers were gynecologic (26.7%), lymphoma (25.7%), pancreas (12.4%), lung (9.8%), and gastric (7.8%). Baseline KS was 2 for the majority of patients (N = 325, 65.3%). Of the full cohort, 41 (8.2%) experienced VTE and 60 (12%) died. In multivariable analysis for VTE, only hsTnT was significantly associated with VTE (p = 0.011); TSH was non-significantly associated (p = 0.09). Patients who developed VTE had higher median hsTnT (11.2 pg/mL) and TSH (1.67 mIU/L) compared to those without VTE (6.9 pg/mL and 1.25 mIU/L, respectively). In multivariate analysis for mortality, elevated CRP (p = 1.1×10⁻⁵), GDF-15 (p = 0.00071), CCL13 (p = 0.0079), and NT-proBNP (p = 0.0099) were strongly associated with increased mortality. Median levels among those who died versus those who survived were: CRP (16.7 vs. 6.2 mg/L), GDF-15 (2645 vs. 1576 pg/mL), CCL13 (28.4 vs. 21.5 pg/mL), and NT-proBNP (251 vs. 102 pg/mL). For the composite outcome of VTE or death, CRP (p = 0.000011), GDF-15 (p = 0.0014), and hGH (p = 0.038) were the most significantly associated. Patients who experienced VTE or death had higher median levels compared to those without events: CRP (16.1 vs. 5.8 mg/L), GDF-15 (2413 vs. 1435 pg/mL), NT-proBNP (228 vs. 93 pg/mL), CCL13 (27.4 vs. 20.5 pg/mL), and hGH (0.51 vs. 0.38 ng/mL).Conclusions: Of previously identified candidate biomarkers, only hsTnT was significantly associated with VTE in this analysis of already-high-risk individuals (minimum KS of 2), with higher median levels observed in those who developed VTE. Elevated levels of CRP, GDF-15, NT-proBNP, and CCL13/MCP-4 were significantly associated with increased risk of mortality and the composite outcome of VTE or death, with affected patients showing notably higher median concentrations. These biomarkers need further study for their potential role in identifying individuals at risk for worse outcomes, and to inform personalized strategies for thromboprophylaxis and prognosis in oncology.

BACKGROUND:Limited language proficiency is an established barrier to research participation among racialized populations. While prior studies have highlighted the underrepresentation of racialized populations in venous thromboembolism (VTE) research, the impact of limited language proficiency as a reason for nonconsent among eligible patients is unknown. OBJECTIVES:To determine the impact of language barrier as the primary reason for VTE research non-participation. METHODS:We reviewed all prospective VTE studies conducted at a research-intensive academic thrombosis research program in Canada between 2014 and 2024. Studies with screening logs that systematically and consecutively captured eligibility assessment and reasons for nonconsent were included. Primary outcome was nonconsent of a screen-eligible patient due to limited language proficiency as the reported reason. We derived pooled estimates of nonconsent due to limited language proficiency as a proportion of consented participants and determined subgroup rates by phase of VTE management, associated medical conditions, and recruitment settings. RESULTS:Screening logs of 28 studies with 22 057 screening events, 8317 screen-eligible patients, and 3320 consented participants were included. For every 100 consented participants, 3.2 (95% CI, 2.0-5.3) screen-eligible individuals were unable to provide consent due to limited language proficiency. Rates of nonconsent were highest in studies involving cancer (5.6 per 100 participants; 95% CI, 2.9-10.4) and in studies recruiting patients from ambulatory settings outside of the thrombosis clinic (10.8 per 100 participants; 95% CI, 4.8-22.6). CONCLUSION:Language proficiency is a key barrier to VTE research participation. Urgent implementation of targeted interventions aimed at mitigating linguistic barriers is essential to ensure equitable opportunities for VTE research participation for racialized patients disproportionately affected by language proficiency.

BACKGROUND:Diagnosing venous thromboembolism (VTE) in patients with previous VTE is challenging. Only approximately 15% of these patients have a VTE recurrence ruled out without imaging, as compared with >30% in patients with a suspected first episode. Clinical decision rules (CDRs) are not well studied in this population. The aim was to assess the performance of existing CDRs (Wells and Geneva scores) in these patients. METHODS:This international prospective multicenter observational cohort study of outpatients with suspected VTE recurrence was conducted in 8 sites (November 2014-January 2019) (clinicaltrials.gov: NCT02297373). The primary outcome was the performance of CDRs. Secondary outcome included the diagnostic yield of D-dimers. Suspected recurrent VTE were adjudicated. Follow-up was 3 months. RESULTS:In total, 723 patients were included. Among patients with suspected isolated deep venous thrombosis (DVT), 4 of 67 patients (6.0%), 39 of 186 patients (21.0%), and 65 of 148 patients (43.9%) had recurrent VTE in the low, moderate, and high probability groups, respectively. Among patients with suspected isolated pulmonary embolism, 11 of 83 patients (13.3%), 56 of 160 patients (35.0%), and 12 to 25 patients (48.0%) had VTE recurrence in the low, moderate, and high probability groups (Wells), respectively. In patients with suspected isolated DVT and negative D-dimers, 2 of 65 patients, 3.1% (95% CI: 0.4%-10.7%) in the low and moderate probability groups had recurrent VTE at enrollment. In patients with suspected pulmonary embolism ± DVT and negative D-dimers, no recurrent VTE was diagnosed: 0 of 82, 0.0% (95% CI: 0.0%-4.4%). CONCLUSION:CDRs were able to characterize patients with increasing VTE prevalence. The efficiency and safety in ruling out recurrent VTE without imaging were lower than for suspected first VTE.

Background Guidelines recommend extended anticoagulation after a first unprovoked venous thromboembolism (VTE) for individuals at low risk of bleeding. However, racial disparities in bleeding risks during extended treatment remain understudied. Objectives To compare risks of anticoagulant-associated bleeding and performance of a risk assessment model by racial group during extended VTE treatment. Methods We analyzed 2 prospective cohorts of patients (223 Black participants and 4314 White participants) with a first unprovoked/weakly provoked VTE who continued anticoagulation after ≥3 months of initial treatment. Primary outcome was adjudicated International Society on Thrombosis and Haemostasis-defined major bleeding. Secondary outcomes included intracranial hemorrhage, fatal bleeding, and clinically relevant nonmajor bleeding. We determined incidence and hazard ratios (HRs) by race, then adjusted for bleeding risk factors that included the Creatinine, Hemoglobin, Age, antiPlatelet model. Results Black participants had higher prevalence of bleeding risk factors and a 1.9-fold higher risk of major bleeding (HR, 1.87; 95% CI, 1.04-3.36) compared with White participants. Adjustment attenuated racial difference for major bleeding but not intracranial hemorrhage (adjusted HR, 2.35; 95% CI, 1.23-4.48). Among those classified as low risk by Creatinine, Hemoglobin, Age, antiPlatelet model, Black participants had numerically higher major bleeding incidence than White participants (2.5 vs 1.1 per 100 person-years). We did not observe racial disparities in fatal bleeding or clinically relevant nonmajor bleeding. Conclusion Black individuals on extended anticoagulation have higher risk of major bleeding compared with White individuals. This effect appears to persist in those classified as low risk for bleeding. Risk assessment models for anticoagulant-associated bleeding that are generalizable to racialized populations are needed.

ProblemDespite increasing recognition of the importance of quality and patient safety in academic medicine, challenges remain with ensuring physician participation in quality assurance and quality improvement efforts, such as lack of compensation and enabling resources. An organizational culture that includes physician leadership and a supportive infrastructure is needed to encourage physician backing of quality and patient safety initiatives.ApproachThe authors describe the development of a robust quality and patient safety program in the Department of Medicine at The Ottawa Hospital over the past 7 years and highlight how the department changed its organizational culture by prioritizing quality and patient safety and establishing the necessary infrastructure to support this program. Program development was characterized by 4 overarching themes: incentives, administrative structure and physician leadership, training and support, and system enhancements.OutcomesAs a result of the program, the department broadly implemented a standardized framework for conducting quality committee meetings and morbidity and mortality rounds and reviewing patient safety incidents and patient experience across its 16 divisions. This has led to 100% departmental compliance on corporate quality assurance metrics each year (e.g., regular multidisciplinary divisional quality committee meetings), along with physician participation in formal quality improvement initiatives that align with larger corporate goals.Next StepsThe authors reflect on lessons learned during the implementation of the program and the essential elements that contributed to its success. Next steps for the program include using a centralized repository of quality and patient safety data, including patient safety incident dashboards, to encourage greater divisional collaboration on quality improvement initiatives and continuous institutional learning over time. Another important avenue will be to create an academic hub for excellence in quality and a formal approach to reward and promote physicians for their quality work.

BACKGROUND:Thus far, all the clinical models developed to predict major bleeding in patients on extended anticoagulation therapy use the baseline predictors to stratify patients into different risk groups. Therefore, these models do not account for the clinical changes and events that occur after the baseline visit, which can modify risk of bleeding. However, it is difficult to develop predictive models from the routine follow-up clinical interviews, which are irregular sequences of multivariate time series data. OBJECTIVES:To demonstrate that deep learning can incorporate patient time series follow-up data to improve prediction of major bleeding. METHODS:We used the baseline and follow-up data that were collected over 8 years in a longitudinal cohort study of 2542 patients, of whom 118 had major bleeding. Four supervised neural network-based machine-learning models were trained on the baseline, follow-up, or both datasets using 70% of the data. The performance of these models was evaluated, along with modified versions of 6 previously developed clinical models, on the remaining 30% of the data. RESULTS:An ensemble of feedforward and recurrent neural networks that used the baseline and follow-up data was the best-performing model, achieving a sensitivity and a specificity of 61% and 82%, respectively, in identifying major bleeding, and it outperformed the previously developed clinical models in terms of area under the receiver operating characteristic curve (82%) and area under the precision-recall curve (14%). CONCLUSION:Time series follow-up data can improve major bleeding prediction in patients on extended anticoagulation therapy.

Recent advances in therapy and the promulgation of multidisciplinary pulmonary embolism teams show great promise to improve management and outcomes of acute pulmonary embolism (PE). However, the absence of randomized evidence and lack of consensus leads to tremendous variations in treatment and compromises the wide implementation of new innovations. Moreover, the changing landscape of health care, where quality, cost, and accountability are increasingly relevant, dictates that a broad spectrum of outcomes of care must be routinely monitored to fully capture the impact of modern PE treatment. We set out to standardize data collection in patients with PE undergoing evaluation and treatment, and thus establish the foundation for an expanding evidence base that will address gaps in evidence and inform future care for acute PE. To do so, >100 international PE thought leaders convened in Washington, DC, in April 2022 to form the Pulmonary Embolism Research Collaborative. Participants included physician experts, key members of the US Food and Drug Administration, patient representatives, and industry leaders. Recognizing the multidisciplinary nature of PE care, the Pulmonary Embolism Research Collaborative was created with representative experts from stakeholder medical subspecialties, including cardiology, pulmonology, vascular medicine, critical care, hematology, cardiac surgery, emergency medicine, hospital medicine, and pharmacology. A list of critical evidence gaps was composed with a matching comprehensive set of standardized data elements; these data points will provide a foundation for productive research, knowledge enhancement, and advancement of clinical care within the field of acute PE, and contribute to answering urgent unmet needs in PE management. Evidence produced through the Pulmonary Embolism Research Collaborative, as it is applied to data collection, promises to provide crucial knowledge that will ultimately produce a robust evidence base that will lead to standardization and harmonization of PE management and improved outcomes.

Patients with cancer have an increased risk of venous thromboembolism (VTE). Currently, several VTE risk prediction tools have been developed to identify candidates for primary VTE thromboprophylaxis. However, the availability of reliable and highly discriminatory prediction models for VTE risk assessment in cancer patients is limited, warranting further improvement of VTE risk stratification strategies. The implementation of biomarkers in risk assessment models might lead to refined VTE risk prediction, but it remains to be more comprehensively investigated. In this systematic review and meta-analysis, we aimed to evaluate and summarize all candidate biomarkers and their association with cancer-associated VTE. We conducted an electronic search in Medline, EMBASE and Cochrane central databases for studies that evaluated biomarkers in adult patients with cancer from inception to September 26 th 2022. We included observational and interventional studies reporting on subsequent VTE occurring after a cancer diagnosis. The baseline or index event of the biomarker measurements had to be definitively and uniformly applied to all enrolled patients. Two reviewers independently screened titles, abstracts and full-text articles for inclusion. Median differences (for continuous measures) and Odds Ratios (OR) (for dichotomous cut-off measures) with 95% confidence intervals (95% CI) were estimated and pooled using random-effects models. We assessed each studies risk of bias using the Quality in Prognostic Studies (QUIPS) risk of bias tool. Our search identified 4274 studies that were screened for inclusion (Figure 1). Following the screening, 109 studies (with 520 biomarker measurements) met the inclusion criteria and were included in the systematic review. Of these, 51 studies (with 174 biomarker measurements) were included in the meta-analysis. The majority of the studies were cohort studies (n=47; 32 prospective and 15 retrospective), while the other 4 studies were nested case-control studies. Eighteen studies had a study population of mixed cancer types and the remaining studies had a study population of specific cancer types, including: lung (n=6), gynecologic (n=5), breast (n=3), stomach (n=3), lymphoma (n=2), myeloma (n=2), ovarian (n=2), pancreas (n=2), brain (n=1), colorectal (n=1), gastrointestinal (n=1), genitourinary (n=1), gynecologic or breast (n=1), head and neck (n=1), liver (n=1), and prostate (n=1). We calculated the median difference and 95% CI for 23 different biomarkers. Cancer patients who experienced subsequent VTE events had significantly higher pre-treatment factor VIII activity, peak thrombin, platelet count and prothrombin fragment F1+2 levels compared to patients who did not experience VTE events (Table 1). Pre-treatment d-dimer levels were also higher in cancer patients who developed VTE, however, considerable heterogeneity was observed (Table 1). Contrastingly, pre-treatment hemoglobin, lag time - thrombin generation, prothrombin time and time to peak thrombin levels were significantly lower in those experiencing VTE events compared to patients who did not experience any events (Table 1). D-dimer levels on day-1 after cancer surgery were reported in two studies which, when pooled, revealed that cancer patients with subsequent VTE had higher d-dimer levels post-operatively compared to those with no events (Table 1). Moreover, pre-treatment hemoglobin levels 100 g/L was significantly associated with future VTE risk [OR: 1.42 (95%CI: 1.03-1.97), I 2=0%, n=11] while neutrophil lymphocyte ratio 3 was associated, yet insignificant [OR: 1.60 (95%CI: 0.99-2.60), I 2=43%, n=4]. Pre-treatment platelet count 350 x 10 9/L and white blood count levels 11 x 10 9/L were not significantly associated with future VTE risk [OR: 0.84 (95%CI: 0.66-1.06), I 2=0%, n=9 and 1.32 (0.86-2.03), I 2=56%, n=8, respectively]. From the 51 studies included in the meta-analyses, 27 studies had a low risk of bias, 19 studies had a moderate risk of bias and 5 studies had a high risk of bias. In conclusion, nine blood biomarkers were found to be significantly associated with VTE in cancer patients. Their utility as predictors of VTE in thrombotic risk assessment models may help in optimising VTE prediction and should be further explored in future studies.

Background: A decision to stop or continue anticoagulation after 3 months of anticoagulation for venous thromboembolism (VTE) should be made by weighing individual risks of recurrence and bleeding.Objectives: To determine the optimal ratio of recurrence risk reduction to increase the risk of bleeding in terms of maximizing quality-adjusted life years (QALYs) gained.Methods: Using a microsimulation model, outcomes within 5 years were simulated after assigning extended treatment if absolute recurrence risk reduction outweighed absolute increase in clinically relevant bleeding risk (International Society on Thrombosis and Haemostasis definition), weighted by a certain ratio. Data were simulated based on the Bleeding Risk Study, a prospective cohort including patients after >= 3 months of anticoagulation for unprovoked VTE or provoked VTE with history of VTE. The VTE-PREDICT risk score was used to estimate 5-year risks of recurrent VTE and clinically relevant bleeding.Results: Among 10,000 individuals (mean age, 60.2 years, 36% female), the ratio of 0.90 (95% CI, 0.51-3.40; ie, bleeding is considered 0.90 the severity of recurrent VTE), with 99% of patients assigned extended anticoagulation, was considered optimal and resulted in 93 (95% CI, -23 to 203) additional QALYs compared with the least favorable ratio (5.10, 0% extended anticoagulation). At the optimal ratio, treatment based on VTE-PREDICT yielded 44 (95% CI, -69 to 157) additional QALYs versus standard of care.Conclusion: With the current evidence, the optimal ratio between relevant bleeding risk and absolute recurrence risk reduction remains uncertain. Our results confirm that clinical equipoise exists regarding the decision to stop or continue anticoagulation after initial VTE treatment, emphasizing the importance of shared decision-making.

In the general population, individuals with an inherited thrombophilia have a higher risk of thrombosis, but the effect of inherited thrombophilia on the risk of cancer-associated venous thromboembolism (VTE) remains controversial. Our objective was to determine the risk of VTE in cancer patients with inherited thrombophilia. We conducted a systematic review and meta-analysis of studies reporting on VTE after a cancer diagnosis in adult patients who were tested for inherited thrombophilia. In September 2022, we searched Medline, EMBASE, and Cochrane Central. Two reviewers screened the abstracts/full texts and assessed study quality using the Quality in Prognostic Studies tool. We used Mantel-Haenszel random-effects models to estimate pooled odds ratios (OR) of VTE and 95% confidence intervals (95%CI). We included 37 and 28 studies in the systematic review and meta-analysis, respectively. Most studies focused on specific cancer types and hematologic malignancies were rare. The risk of VTE was significantly higher in cancer patients with non-O (compared with O) blood types (OR: 1.56 [95% CI: 1.28-1.90]), Factor V Leiden, and Prothrombin Factor II G20210A mutations compared with wild types (OR: 2.28 [95% CI: 1.51-3.48] and 2.14 [95% CI: 1.14-4.03], respectively). Additionally, heterozygous and homozygous methylenetetrahydrofolate reductase C677T had ORs of 1.50 (95% CI: 1.00-2.24) and 1.38 (95% CI: 0.87-2.22), respectively. Among those with Plasminogen-Activator Inhibitor-1 4G/5G, Vascular Endothelial Growth Factor (VEGF) A C634G, and VEGF C2578A mutations, there was no significant association with VTE. In conclusion, this meta-analysis provided evidence that non-O blood types, Factor V Leiden, and Prothrombin Factor II G20210A mutations are important genetic risk factors for VTE in cancer patients.

Background: After 3 months of anticoagulation for venous thromboembolism (VTE), the decision needs to be made whether to stop anticoagulation or extend treatment indefinitely. The VTE-PREDICT calculator can be used to estimate individual risks of VTE recurrence and bleeding to guide this decision. Objectives: To evaluate the impact of predicted individual risks of recurrence and bleeding on clinicians’ decisions on anticoagulation duration and to assess usefulness of the VTE-PREDICT calculator. Methods: A randomized controlled trial and within-subject study was conducted among clinicians treating VTE patients. The clinicians were asked to complete an online survey containing 6 fictional case vignettes. Group A proposed anticoagulant duration for each case without additional information first and subsequently after seeing calculator-predicted risks (within-subject analysis). Group B was directly provided with calculator risks and proposed treatment duration for each case vignette (for comparison with group A results in a randomized controlled trial analysis). Then, group B received questions on usefulness and credibility of the calculator. Results: Forty-five clinicians were assigned to group A and 48 to B. Overall, group A did not propose different anticoagulation durations than group B. However, individual clinicians in group A changed proposed duration in 35% of the cases after seeing the calculator risks. The calculator was considered useful and credible by most clinicians. Conclusion: Overall, use of the VTE-PREDICT calculator did not affect proposed anticoagulation duration. However, individual clinicians frequently changed their proposed duration after using the calculator, especially for patients with high bleeding risk.

BACKGROUND AND AIMS:Home treatment is considered safe in acute pulmonary embolism (PE) patients selected by a validated triage tool (e.g. simplified PE severity index score or Hestia rule), but there is uncertainty regarding the applicability in underrepresented subgroups. The aim was to evaluate the safety of home treatment by performing an individual patient-level data meta-analysis. METHODS:Ten prospective cohort studies or randomized controlled trials were identified in a systematic search, totalling 2694 PE patients treated at home (discharged within 24 h) and identified by a predefined triage tool. The 14- and 30-day incidences of all-cause mortality and adverse events (combined endpoint of recurrent venous thromboembolism, major bleeding, and/or all-cause mortality) were evaluated. The relative risk (RR) for 14- and 30-day mortalities and adverse events is calculated in subgroups using a random effects model. RESULTS:The 14- and 30-day mortalities were 0.11% [95% confidence interval (CI) 0.0-0.24, I2 = 0) and 0.30% (95% CI 0.09-0.51, I2 = 0). The 14- and 30-day incidences of adverse events were 0.56% (95% CI 0.28-0.84, I2 = 0) and 1.2% (95% CI 0.79-1.6, I2 = 0). Cancer was associated with increased 30-day mortality [RR 4.9; 95% prediction interval (PI) 2.7-9.1; I2 = 0]. Pre-existing cardiopulmonary disease, abnormal troponin, and abnormal (N-terminal pro-)B-type natriuretic peptide [(NT-pro)BNP] at presentation were associated with an increased incidence of 14-day adverse events [RR 3.5 (95% PI 1.5-7.9, I2 = 0), 2.5 (95% PI 1.3-4.9, I2 = 0), and 3.9 (95% PI 1.6-9.8, I2 = 0), respectively], but not mortality. At 30 days, cancer, abnormal troponin, and abnormal (NT-pro)BNP were associated with an increased incidence of adverse events [RR 2.7 (95% PI 1.4-5.2, I2 = 0), 2.9 (95% PI 1.5-5.7, I2 = 0), and 3.3 (95% PI 1.6-7.1, I2 = 0), respectively]. CONCLUSIONS:The incidence of adverse events in home-treated PE patients, selected by a validated triage tool, was very low. Patients with cancer had a three- to five-fold higher incidence of adverse events and death. Patients with increased troponin or (NT-pro)BNP had a three-fold higher risk of adverse events, driven by recurrent venous thromboembolism and bleeding.

Background: Anticoagulation therapy is the mainstay of therapy for patients with venous thromboembolism (VTE). However, continuing or stopping anticoagulants after the first 3 to 6 months is a difficult decision that requires ascertainment of the risk of bleeding and recurrent VTE. Despite the development of several statistical models to predict bleeding, the benefit of machine learning (ML) models has not been investigated in depth. Objectives: To assess the benefits of ML algorithms in bleeding risk evaluation in VTE patients and gain insight into their baseline information. Methods: The baseline clinical, demographic, and genotype information was collected for 2542 patients with VTE who were on extended anticoagulation therapy. Six unsupervised dimensionality reduction and clustering ML algorithms were used to visualize and cluster the data for patients with major bleeding (118 patients) and nonbleeders. Eight supervised ML algorithms were trained and compared with the previously derived clinical models using a 5-fold nested cross-validation scheme. Results: The baseline dataset for bleeders and nonbleeders showed a high degree of similarity. Two novel clusters were discovered within the dataset for bleeders based on the presence of isolated pulmonary embolism or isolated deep vein thrombosis, though the difference in bleeding risks was not statistically significant (P = .32). The supervised analysis showed that the ML and clinical models have similar discrimination (c-statistics, -62%) and calibration performance (Brier score, 0.045). Conclusion: The clinical variables recorded at baseline are not distinctive enough to improve bleeding prediction beyond the performance of the existing models, and other strategies or data modalities should be considered.

Background:Contemporary guidelines recommend extended-duration anticoagulation among patients with a first unprovoked venous thromboembolism (VTE). Little is known about whether this recommendation aligns with patient values after a bleeding complication.Objectives:To explore the experiences, values, and decisional needs of patients with unprovoked VTE related to extended-duration treatment after an anticoagulant-associated bleed.Methods:In this descriptive, qualitative study, face to face online semistructured interviews were conducted with patients with unprovoked VTE who had experienced bleeding and continued anticoagulant treatment in one academic hospital in Canada. Data were analyzed using directed content analysis to identify themes. Themes were mapped onto the Ottawa Decisional Support Framework to identify decisional needs.Results:Between September and December 2021, 14 patients were interviewed (age 41-69 years; 9 females). Many patients were not aware of the option to stop anticoagulation and had limited understanding of the decision about treatment duration. Despite the negative quality-of-life impact of clinically relevant bleeding during VTE treatment, the majority continued anticoagulation due to emotional trauma of VTE diagnosis, a perception that bleeding would be more manageable than VTE recurrence, a desire to maintain a connection to subspecialty care or non-VTE related benefits (eg, cancer diagnosis, protection from COVID-19). Patients' decisional needs included lack of choice awareness, inadequate support for participation, lack of personalized risk stratification, and inadequate information on monitoring and managing heavy menstrual bleeding.Conclusion:Despite the impact of anticoagulant-associated bleeding on quality of life, patients preferred continuing with anticoagulation for reasons extending beyond secondary VTE prevention. Effective decision-support interventions are needed to address unmet decisional needs.