Management and outcomes in patients with tumor thrombus: A retrospective cohort study.

BACKGROUND: Tumor thrombus can be associated with an increased risk of venous thromboembolism (VTE) and poor prognosis. The risks and benefits of anticoagulation remain unclear. METHODS: We conducted a single-center retrospective cohort study in patients with tumor thrombus in 2019-2022. All patients were followed for 12 months from the diagnosis of tumor thrombus or until death if death occurred earlier. The primary outcome was the percentage of patients prescribed any dose of anticoagulation for tumor thrombus (or concurrent bland thrombus/VTE). The secondary outcomes included new thrombosis, major bleeding (MB), clinically relevant non-major bleeding (CRNMB), and mortality. We calculated the 6- and 12-month cumulative incidence of outcomes with 95% confidence interval (CI) and compared those given anticoagulation versus not, considering death as a competing risk. RESULTS: We included 211 patients, among whom 106 (50.2%) (95% CI: 47.9-52.6) were given anticoagulation for tumor thrombus or concurrent VTE (present in 21.8%). The most common type of cancer was hepatocellular carcinoma (28%). Splanchnic veins were the most commonly involved (49.3%). Anticoagulation was more likely used if tumor thrombus involved the inferior vena cava, the heart, with concurrent VTE, or if thrombosis service was consulted. The overall 12-month incidence of new VTE was 11.4% (95% CI 7.3-16.5), that of MB + CRNMB was 36.6% (95% CI 29.6-43.5), and mortality of 52.5% (95% CI 44.8-59.6), with no significant differences among groups given anticoagulation or not. CONCLUSIONS: Patients with tumor thrombus carry high risks of VTE, bleeding and mortality. The impact of anticoagulation remains unclear.

Impact of limited language proficiency on participation in venous thromboembolism research: A retrospective analysis.

BACKGROUND: Limited language proficiency is an established barrier to research participation among racialized populations. While prior studies have highlighted the under-representation of racialized populations in venous thromboembolism (VTE) research, the impact of limited language proficiency as a reason for non-consent among eligible patients is unknown. 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 non-consent were included. Primary outcome was non-consent of a screen-eligible patient due to limited language proficiency as the reported reason. We derived pooled estimates of non-consents 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, 8,317 screen-eligible patients and 3,320 consented participants were included. For every 100 consented participants, 3.2 (95% CI 2.0 - 5.3) screen-eligible individuals were unable to be consented due to limited language proficiency. Rates of non-consent 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). CONCLUSIONS: 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.

Anticoagulation for the Prevention of Arterial Thromboembolism in Cancer Patients by Primary Tumor Site: A Systematic Review and Meta-Analysis of Randomized Trials.

AIMS: Incidence of arterial thromboembolism (ATE) among ambulatory cancer patients varies by primary tumor site. However, it is unclear whether this alters the benefit-to-harm profile of prophylactic anticoagulation for ATE prevention. Therefore, we systematically evaluated the efficacy and safety of anticoagulants for ATE prevention among ambulatory cancer patients according to the primary tumor site. METHODS AND RESULTS: We conducted a systematic review using Medline, Embase, SCOPUS, and CENTRAL, and included randomized trials comparing prophylactic anticoagulation to no anticoagulation among ambulatory cancer patients who initiated tumor-directed systemic therapy. Incidence of symptomatic ATE (acute ischemic stroke, acute myocardial infarction or peripheral artery occlusion) and major bleeding, as well as risk differences (RDs) attributable to anticoagulation were meta-analyzed by primary tumor site using random-effects modeling. We included 10 randomized controlled trials with 9,875 patients with follow-up ranging from 3.3 to 68 (median 6.6) months. While prophylactic anticoagulation did not reduce ATE risks overall (RD -0.49%; 95% CI -0.49% to 0.01%; I2=0%), it conferred a protective effect among pancreatic cancer patients (RD -3.2%; 95%CI -5.7% to -0.8%; I2=0%) without a detectable increase in major bleeding (RD -1.4%; 95% CI -4.6% to 1.8%; I2=0%). Prophylactic anticoagulation was not associated with ATE risk reduction in other tumor sites. CONCLUSION: Based on available evidence, prophylactic anticoagulation did not reduce ATE risk among ambulatory cancer patients overall. However, we observed lower incidence of ATE among pancreatic cancer patients randomized to receive anticoagulation. Prophylactic anticoagulant use to reduce ATEs in pancreatic cancer should be evaluated in future research.

Inferior vena cava filter use at a large community hospital: a retrospective cohort study.

Inferior vena cava (IVC) filters are considered when patients with venous thromboembolism (VTE) develop a contraindication to anticoagulation. Use of IVC filters is increasing, despite associated complications and lack of data on efficacy in reducing VTE-related mortality. We characterized the pattern of IVC filter use at a large community hospital between 2018 and 2022. Specifically, we assessed the indications for IVC filter insertion, filter removal rates, and filter-associated complications. Indications for IVC filters were compared to those outlined by current clinical practice guidelines. We reviewed 120 consecutive filter placement events. The most common indications included recent VTE and active bleeding (40.0%) or need for anticoagulation interruption for surgery (25.8%). Approximately one-third (30.0%) of IVC filters were inserted for indications either not supported or addressed by guidelines. Half (50.0%) of patients had successful removal of their IVC filter. At least 13 patients (10.8%) experienced a filter-related complication. In a large community-based practice, nearly one-third of IVC filters were inserted for indications not universally supported by current practice guidelines. Moreover, most IVC filters were not removed, raising the risk of filter-associated complications, and supporting the need for development of comprehensive guidelines addressing use of IVC filters, and post-insertion monitoring practices.

Circulating Blood Biomarkers and Risk of Venous Thromboembolism in Cancer Patients: A Systematic Review and Meta-Analysis.

BACKGROUND: Cancer patients have an increased risk of venous thromboembolism (VTE). Currently, the availability of highly discriminatory prediction models for VTE in cancer patients is limited. The implementation of biomarkers in prediction models might lead to refined VTE risk prediction. In this systematic review and meta-analysis, we aimed to evaluate candidate biomarkers and their association with cancer-associated VTE. METHODS: We searched Medline, EMBASE, and Cochrane Central for studies that evaluated biomarkers in adult cancer patients from inception to September 2022. We included studies reporting on VTE after a cancer diagnosis with biomarker measurements performed at a defined time point. Median/mean differences (for continuous measures) and odds ratios (for dichotomous measures) with 95% confidence intervals were estimated and pooled using random-effects models. RESULTS: We included 113 studies in the systematic review. Of these, 50 studies were included in the meta-analysis. We identified two biomarkers at cancer diagnosis (factor VIII and time to peak thrombin), three biomarkers pre-chemotherapy (D-dimer, fibrinogen, and mean platelet volume), and one biomarker preoperatively (platelet count) that had significant median or mean differences. Additionally, we found that hemoglobin <100 g/L and white blood count >11 × 109/L were significantly associated with future VTE risk only when measured at cancer diagnosis. Pre-chemotherapy neutrophil-to-lymphocyte ratio ≥3 and preoperative platelet count ≥400 × 109/L were also found to be associated with future VTE risk. CONCLUSION: In conclusion, this study identified nine candidate blood biomarkers that may help in optimizing VTE prediction in cancer patients that should be further explored in future studies.

Risk of recurrent venous thromboembolism and bleeding in patients with acute isolated subsegmental pulmonary embolism.

INTRODUCTION: Approximately 10 % of all diagnosed pulmonary embolism are isolated to the subsegmental vessels. The risk of recurrent venous thromboembolism (VTE) in patients with an acute subsegmental pulmonary embolism (SSPE) managed with or without anticoagulant therapy remains poorly understood. METHODS: This is an observational cohort study including consecutive adult patients diagnosed with acute isolated SSPE between June 01, 2019, and August 31, 2022. We excluded patients with a concomitant diagnosis of deep vein thrombosis and those who had an indication for long-term anticoagulation. The primary outcome was objectively confirmed recurrent VTE. RESULTS: Overall, 118 patients with acute SSPE were included in the analysis. The mean (± standard deviation [SD]) age of the participants was 59 ± 17 years and 44 % of them had active cancer. Mean (±SD) duration of follow-up was 438 ± 426 days. Seventy-seven patients (65 %) were initially treated with anticoagulation, whereas 41 patients (35 %) were not. Of the 77 patients receiving anticoagulant therapy, 23 (30 %) received extended-duration anticoagulation (beyond 3 months) for secondary prevention. Overall, recurrent VTE events occurred in 6/118 (5 %, 95 % CI 2.4 to 10.7) patients. Four events (4/77 = 5.2 %, 95 % CI 2.0 to 12.6) occurred in initially treated patients. Two recurrent VTE occurred in patients initially left untreated (2/41 = 4.9 %, 95 % CI 1.4 to 16.1). Half of the recurrent VTE occurred in patients with active cancer. CONCLUSIONS: Most patients diagnosed with an acute SSPE received anticoagulation. The incidence of recurrent VTE detected over time was relatively high, especially in patients with cancer.

Primary prevention of venous thromboembolism in ambulatory cancer patients: recent advances and practical implications.

Venous thromboembolism (VTE) is a common complication in ambulatory cancer patients receiving anticancer therapies. Many patient-, cancer-, and treatment­related factors along with specific biomarkers can be associated with an increased risk of VTE in patients with cancer. Risk assessment models, such as the Khorana score, serve as valuable tools to aid in the identification of patients with cancer who are at high risk of VTE. Two randomized controlled trials have evaluated the efficacy of primary thromboprophylaxis with low­dose direct oral anticoagulants, apixaban and rivaroxaban, to reduce the risk of VTE in ambulatory patients with cancer who are at intermediate to high risk of VTE identified by the Khorana score. This narrative review summarizes the literature on the risk factors and risk assessment process for VTE, and the use of primary thromboprophylaxis in ambulatory cancer patients. We also outline important practical considerations for initiating primary thromboprophylaxis in this population.

A meta-analysis to assess the risk of bleeding and thrombosis following chimeric antigen receptor T-cell therapy: Communication from the ISTH SSC Subcommittee on Hemostasis and Malignancy.

BACKGROUND: Chimeric antigen receptor T-cell (CAR T-cell) therapy is increasingly utilized for treatment of hematologic malignancies. Hematologic toxicities including thrombosis and bleeding complications have been reported. Accurate estimates for thrombotic and bleeding outcomes are lacking. OBJECTIVES: We performed a systematic review and meta-analysis in patients who received CAR T-cell therapy for an underlying hematologic malignancy with the objective to: a) assess the thrombosis and bleeding risk associated with CAR T-cell therapy, b) assess the impact of CRS and ICANS on the risks of thrombosis and bleeding, and c) assess the safety of anticoagulant or antiplatelet use in the period following treatment with CAR T-cell therapy. METHODS: We searched MEDLINE, EMBASE, and Cochrane CENTRAL up to February 2022 for studies reporting thrombotic or bleeding outcomes in patients receiving CAR T-cell therapy. Pooled event rates were calculated using a random-effects model. We performed subgroup analyses stratified by follow-up duration, CAR T-cell target antigen, and underlying hematologic malignancy. RESULTS: We included 47 studies with a total of 7040 patients. High heterogeneity between studies precluded reporting of overall pooled rates of thrombotic and bleeding events. In studies with follow-up duration of ≤6 months, the pooled incidence of venous thrombotic events was 2.4% (95% CI, 1.4%-3.4%; I2 = 0%) per patient-month, whereas the rate was 0.1% (95% CI, 0%-0.1%; I2 = 0%) per patient-month for studies with longer follow-up periods (>6 months). The pooled incidences of any bleeding events per patient-month in studies with follow-up duration of ≤6 months and >6 months were 1.9% (95% CI, 0.6%-3.1%; I2 = 78%) and 0.3% (95% CI: 0%-0.8%, I2 = 40%), respectively. Secondary analyses by CAR T-cell target antigen, underlying malignancy, and primary outcome of the studies did not reveal significant differences in the rates of thromboembolism, any bleeding events, or major bleeding events. CONCLUSION: The risk of both thrombosis and bleeding following CAR T-cell therapy appears to be highest in the initial months following infusion.

Inherited thrombophilia gene mutations and risk of venous thromboembolism in patients with cancer: A systematic review and meta-analysis.

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.

Management strategies in persons with inherited haemophilia requiring antithrombotic therapy: A scoping review.

BACKGROUND: Thromboembolic events are increasingly reported in the aging haemophilia population. The purpose of this study was to understand current practices and identify knowledge and research gaps in the management of persons with haemophilia requiring antithrombotic therapy for cardiovascular disorders (CVD) or venous thromboembolism (VTE). METHODS: We searched MEDLINE, EMBASE and Scopus for studies reporting on more than two patients with inherited haemophilia A or B, without inhibitors, requiring antithrombotic therapy for CVD or VTE. Data were extracted by two independent reviewers and analysed using descriptive statistics and narrative synthesis. RESULTS: We included 32 studies reporting on 432 persons with haemophilia. Three themes described the observed practice variation: (1) Difficulty weighing competing bleeding and thrombotic risks; (2) Tensions in providing standards of care and minimizing bleeding risk; (3) Advocacy for individualized strategies and multidisciplinary care. Different management strategies were used to treat persons with haemophilia in the setting of thromboembolic events, such as avoiding or choosing lower intensity antithrombotic therapy, or procedural alternatives to antithrombotic therapy. Initiation or alteration in haemostatic therapies along with antithrombotic therapy were common strategies and reported in 30 studies. However, data on target factor levels and bleeding and thrombotic events were largely missing. DISCUSSION: Our scoping review highlights unmet needs in the management of an aging population of persons with haemophilia with increasing prevalence of CVD and VTE. Management is inconsistent and divergent from those of non-haemophilic patients. Prospective data are needed to inform optimal and evidence-based management strategies of CVD and VTE in persons with haemophilia.

Management of catheter-related upper extremity deep vein thrombosis in patients with cancer: a systematic review and meta-analysis.

BACKGROUND: Patients with cancer commonly require a central venous catheter, which is associated with an increased risk of venous thromboembolism (VTE). Despite the frequent occurrence, the optimal anticoagulation management and outcomes for patients with cancer and catheter-related upper extremity deep vein thrombosis (DVT) are unclear. OBJECTIVE: We performed a systematic review and meta-analysis to evaluate the rates of recurrent VTE and bleeding in patients with cancer and catheter-related upper extremity DVT. METHODS: We searched MEDLINE, Embase, Scopus, and CENTRAL from inception to June 2, 2023. The primary efficacy outcome was recurrent VTE, and the primary safety outcome was major bleeding. The incidence rates (with 95% CI) of outcomes were pooled using random effects model. RESULTS: We included 29 studies (N = 2,836), among which 5 were prospective. The duration of follow-up and anticoagulation varied considerably. The main long-term anticoagulant used was low molecular weight heparin, followed by direct oral anticoagulants. The pooled 3-month recurrent VTE rate from 14 studies (N = 1,128) was 0.56% (95% CI, 0.10%-3.01%; I2 = 0%). The pooled 3-month major bleeding rate from 10 studies (N = 834) was 2.34% (95% CI, 1.14%-4.76%; I2 = 0%). We were unable to pool event rates beyond 3 months, given high heterogeneity. All studies had serious risk of bias. CONCLUSIONS: Our study demonstrated a relatively low rate of recurrent VTE and moderate rate of major bleeding events within the first 3 months in patients with cancer and catheter-related upper extremity DVT. However, there was significant heterogeneity in the management and reporting after 3 months.

Management of chemotherapy-induced thrombocytopenia: guidance from the ISTH Subcommittee on Hemostasis and Malignancy.

Thrombocytopenia is a common adverse effect of chemotherapy. The development of chemotherapy-induced thrombocytopenia (CIT) is influenced by cancer type and therapy, occurring in approximately one-third of patients with a solid tumor diagnosis and half of all patients with a hematologic malignancy. CIT may complicate the administration of chemotherapy, leading to therapeutic delays or dose reductions. This guidance document, presented by the International Society on Thrombosis and Haemostasis (ISTH) Subcommittee on Hemostasis and Malignancy, provides a comprehensive summary of the evidence and offers direction on the use of thrombopoietin receptor agonists (TPO-RAs) in various settings of CIT, including solid tumors, acute myeloid leukemia, stem cell transplant, and lymphoma. Studies have shown that TPO-RAs can improve platelet counts in CIT, but the clinical benefits of TPO-RA in terms of reducing bleeding, limiting platelet transfusion, avoiding chemotherapy delay, or dose reduction are uncertain. Further research is needed to optimize the selection of appropriate indications and study design to manage thrombocytopenia following chemotherapy.

Periprocedural management of direct oral anticoagulants in patients with atrial fibrillation and active cancer.

BACKGROUND: Cancer and atrial fibrillation (AF) are common concurrent disorders. Direct oral anticoagulants (DOACs) are prescribed to prevent stroke in patients with AF. Patients with cancer often undergo invasive procedures for diagnostic or therapeutic purposes, necessitating interruption of anticoagulation. There are limited data to guide best periprocedural anticoagulation management practices in the setting of active cancer. OBJECTIVES: To describe patient characteristics, periprocedural management, and clinical outcomes in DOAC-treated patients with AF according to active cancer status. METHODS: We conducted descriptive and comparative analyses using data from the PAUSE study. Multivariable logistic regression was used to determine whether active cancer status was an independent risk factor for bleeding outcomes. Covariates were selected a priori based on biological rationale and preexisting knowledge. RESULTS: Patients with active cancer were older (P < .001), more likely to be thrombocytopenic (P = .026), have moderate renal dysfunction (P = .005), and more likely to receive low-dose DOAC therapy (P < .001). A greater proportion of patients with active cancer underwent a high-bleed-risk procedure (P < .001), with longer periprocedural DOAC-interruption intervals (P <.001) and lower preprocedural residual DOAC levels (P = .002). Active cancer was an independent predictor for surgical major bleeding (OR = 2.45; 95% CI, 1.08-5.14) after adjusting for study center, procedure category and bleed risk, thrombocytopenia, hypertension, and the use of a P2Y12 inhibitor. CONCLUSIONS: Active cancer status is associated with an increased risk of surgical major bleeding among DOAC-treated patients with AF undergoing interruption of anticoagulation for elective invasive procedures.

The prevalence of relevant drug-drug interactions and associated clinical outcomes in patients with cancer-associated thrombosis on concurrent anticoagulation and anticancer or supportive care therapies.

BACKGROUND: A main concern in the management of patients with cancer-associated thrombosis (CAT) is drug-drug interactions (DDIs) between anticoagulants and anticancer therapies. Their clinical implications remain unclear. METHODS: To quantify the prevalence of DDIs and risks of recurrent venous thromboembolism (VTE) and bleeding events in patients with CAT on anticoagulation, we conducted a retrospective cohort study in patients with CAT on concurrent anticoagulants and anticancer and/or supportive care therapies. All patients were followed for 6 months from CAT diagnosis or until death (whichever occurred first). The primary outcome was the percentage of patients with anticoagulant DDIs classified as risk C, D, or X in Lexicomp® at any time during the 6 months. Secondary outcomes included recurrent VTE and clinically relevant bleeding events. We calculated the 6-month cumulative incidence of outcomes with 95 % confidence interval (CI) and compared those with and without DDIs, considering death as a competing risk. RESULTS: Among 267 patients included, 111 (41.6 %) had DDIs with anticoagulants at any time during the study. Those on DOACs at any time had more DDIs compared to LMWH (50.9 % vs 19.3 %, p < 0.0001). The 6-month incidence was 8.2 % (95 % CI 5.3-11.9) for recurrent VTE and 6.7 % (95 % CI 4.2-10.2) for clinically relevant bleeding, with no significant differences between groups with or without DDIs. CONCLUSIONS: There are high incidences of DDIs in patients with CAT on anticoagulants, more with DOACs. DDIs classified as risk C, D, or X by Lexicomp® were not associated with recurrent VTE or bleeding events in our cohort.