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3/27/26

ABSTRACT

BACKGROUND: Cancer-associated thrombosis (CAT) is a frequent complication in patients with malignancies. While FXI/FXIa inhibition is efficacious in preventing postoperative venous thromboembolism, its role in tumor cell-induced coagulation is less defined.

OBJECTIVES: We thus aimed to provide mechanistic insights into FXI/FXIa inhibition in tumor cell-induced coagulation activation.

METHODS: Procoagulant activity (PCA) of four different tissue factor (TF) expressing tumor cell lines was analyzed by single-stage clotting and thrombin generation assay in the presence of a FXIa inhibitor, BMS-262084 (BMS), an inhibitory FXI antibody (anti-FXI), or peak and trough concentrations of rivaroxaban or tinzaparin. Further, tumor cell-induced platelet aggregation was recorded. Recombinant human TF (rhTF) served as positive control.

RESULTS: Although BMS and anti-FXI potently inhibited FXIa amidolytic activity, both inhibitors efficiently mitigated rhTF- and tumor cell-induced fibrin clot formation and platelet aggregation only in the presence of low TF PCA. The anticoagulant effects showed an inverse correlation with the magnitude of cellular TF PCA expression. Similarly, BMS markedly interfered with tumor cell-induced thrombin generation, with the most prominent effects on peak and total thrombin. In addition, anticoagulant effects of FXIa inhibition by 10 μM BMS were in a similar range to those obtained by 600 nM rivaroxaban and 1.6 μM tinzaparin at low TF PCA levels. However, rivaroxaban and tinzaparin also exerted marked anticoagulant activity at high TF PCA levels.

CONCLUSIONS: Our findings indicate that FXI/FXIa inhibition interferes with tumor cell-induced coagulation activation only at low TF PCA expression levels, a finding with potential implications for future in-vivo studies.

PMID:37751848 | DOI:10.1016/j.jtha.2023.09.015

05:56

PubMed articles on: Cardio-Oncology

05:56

PubMed articles on: Cancer & VTE/PE

Long-term risk of venous thromboembolism among patients with gastrointestinal non-neoplastic and neoplastic diseases: A prospective cohort study of 484 211 individuals

Am J Hematol. 2023 Sep 27. doi: 10.1002/ajh.27106. Online ahead of print.

ABSTRACT

We conducted a prospective cohort study to examine the associations of 21 gastrointestinal diseases with the risk of incident venous thromboembolism (VTE). The study included 485 936 UK Biobank participants free of baseline VTE. The gastrointestinal diseases were defined by the International Classification of Disease (ICD)-9 and 10 codes with data from the nationwide inpatient data set, the primary care data set, and the cancer registries. Incident VTE cases were defined by ICD-9 and 10 codes with data from the nationwide inpatient data set. Cox proportional hazards regression was used to estimate the associations of baseline gastrointestinal diseases with incident VTE risk. During a median follow-up of 12.0 years, 13 646 incident VTE cases were diagnosed. Eleven gastrointestinal diseases (nine non-neoplastic and two neoplastic) were associated with an increased risk of incident VTE after Bonferroni corrections. The risk of VTE was >50% higher among patients with gallbladder and biliary tract cancer (hazard ratio [HR] 3.15, 95% confidence interval [CI] 95% CI 1.74-5.70), pancreatic cancer (HR 2.84, 95% CI 1.65-4.91), cirrhosis (HR 2.34, 95% CI 1.96-2.79), Crohn's disease (HR 1.61, 95% CI 1.33-1.95), or pancreatitis (HR 1.57, 95% CI 1.31-1.88) compared with individuals without each of these diseases. We observed multiplicative interactions of age, sex, and body mass index with some gastrointestinal diseases (p < .05). A more pronounced, increased risk of VTE was found among younger, female, or obese patients. The study suggests a 50% higher risk of developing VTE among patients with gallbladder and biliary tract cancer, pancreatic cancer, cirrhosis, Crohn's disease, or pancreatitis.

PMID:37753710 | DOI:10.1002/ajh.27106

05:56

PubMed articles on: Cancer & VTE/PE

A Rare Incidence of Hepatocellular Carcinoma With Tumor Thrombus Extending to the Right Heart

Cureus. 2023 Aug 23;15(8):e43965. doi: 10.7759/cureus.43965. eCollection 2023 Aug.

ABSTRACT

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths and the sixth most commonly diagnosed cancer worldwide due to several common risk factors, including hepatitis C virus (HCV), hepatitis B virus (HBV), and other causes of cirrhosis. In HCC, intrahepatic vascular invasion and a tumor thrombus are commonly observed. However, the extrahepatic spread of the tumor thrombus to the heart via the portal vein, hepatic vein, and inferior vena cava (IVC) is rarely reported and is considered a poor prognostic factor. In addition, rarely, there is a risk of cor pulmonale and thromboembolism of the pulmonary vessels. Our patient also presented with this rare complication of HCC. Our patient's clinical presentation was bilateral pedal edema, moderate ascites, and abdominal discomfort with raised jugular venous pressure. These signs and symptoms are related to an impairment of the right heart caused by intracardiac tumor thrombus metastasis, leading to diastolic dysfunction. Based on these findings, echocardiography and abdominal computed tomography (CT) scan were performed with the definitive diagnosis of hepatocellular carcinoma with tumor thrombus metastases in the hepatic vein, inferior vena cava, and right atrium. The management team agreed on a conservative treatment plan based on the advanced stage of the disease and the high risk associated with aggressive treatment modalities. Unfortunately, on day 7 of admission, the patient died from a possible pulmonary embolism that led to cardiopulmonary arrest. This case underscores the importance of screening patients with a high HCC tumor burden with abdominal ultrasound and echocardiography for early detection and timely management.

PMID:37746383 | PMC:PMC10515291 | DOI:10.7759/cureus.43965

05:56

PubMed articles on: Cancer & VTE/PE

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

EClinicalMedicine. 2023 Sep 8;64:102194. doi: 10.1016/j.eclinm.2023.102194. eCollection 2023 Oct.

ABSTRACT

BACKGROUND: The optimal duration of anticoagulation in patients with active cancer and venous thromboembolism (VTE) is unknown. Current clinical guidelines advocate anticoagulant therapy for 3-6 months and to continue anticoagulant therapy for as long as the cancer is active. However, an adequate systematic review on the rate of recurrent VTE after discontinuation of anticoagulant therapy has not been performed.

METHODS: For this systemic review and meta-analysis, we searched Embase.com, Medline (Ovid), Web of Science, Cochrane Library, and Google Scholar, from database inception to February 16, 2023, for studies on anticoagulant therapy in patients with cancer and the recurrence of venous thromboembolism after discontinuation of this therapy. We included randomised controlled trials and cohort studies published in English that reported on patients who met the following: cancer and a first VTE, completed at least 3 months of anticoagulant therapy, were followed after discontinuation of anticoagulant therapy, and with symptomatic recurrent VTE as an outcome during follow-up. Study-level data were requested from study authors. The primary outcome was the rate of recurrent VTE after discontinuation of anticoagulant therapy. A Bayesian random-effects meta-analysis was used to estimate the rate of recurrent VTE per 100 person-years for the pooled studies at different time intervals after discontinuation of anticoagulation therapy. We also calculated the cumulative VTE recurrence rate at different time intervals. Forest plots were mapped and the results were summarized by the median and 95% credible interval (CIs). This study was registered with PROSPERO, CRD42021249060.

FINDINGS: Of 3856 studies identified in our search, 33 studies were identified for inclusion. After requesting study-level data, 14 studies involving 1922 patients with cancer-associated thrombosis were included. The pooled rate of recurrent VTE per 100 person-years after discontinuation of anticoagulant therapy was 14.6 events (95% credible interval 6.5-22.8) in the first three months, decreasing to 1.1 events (95% CI 0.3-2.1) in year 2-3, and 2.2 events (95% CI 0.0-4.4) in year 3-5 after discontinuation of anticoagulant therapy. The cumulative VTE recurrence rate was 28.3% (95% CI 15.6-39.6%) at 1 year; 31.1% (95% CI 16.5-43.8%) at 2 years; 31.9% (95% CI 16.8-45.0%) at 3 years; and 35.0% (95% CI 16.8-47.4%) at 5 years after discontinuation of anticoagulant therapy.

INTERPRETATION: This meta-analysis demonstrates a high rate of recurrent VTE over time after discontinuation of anticoagulant therapy in patients with cancer-associated thrombosis. Our results support the current clinical guidelines to continue anticoagulant therapy in patients with active cancer.

FUNDING: Erasmus MC.

PMID:37731937 | PMC:PMC10507196 | DOI:10.1016/j.eclinm.2023.102194