ABSTRACT

BACKGROUND: Cancer associated venous thromboembolism (Ca-VTE) treatment with anticoagulation is associated with bleeding complications and there are limited data on risk factors. Current models do not provide accurate bleeding risk prediction.

METHODS: UK Clinical Practice Research Datalink data (2008-2020) was used to generate a cohort of patients with anticoagulant initiation for first Ca-VTE. Patients were observed up to 180 days for significant bleeding including major bleeding, and clinically relevant non-major bleeding requiring hospitalisation (CRNMB-H). A scoring scheme was developed from subdistribution hazard ratios, and its discrimination (expressed by the C-statistic) estimated from cross-validation.

RESULTS: 15,749 patients with Ca-VTE and anticoagulant treatment were included. In total, 537 significant bleeding events, 161 major bleeds and 376 CRNMB-H were identified after adjudicated review in 4914 person-years of observation. Incidence rates of 3.3 and 7.7 per 100 person-years were noted for major bleeding and CRNMB-H. Independent predictors of significant bleeding were cancer of the bladder, central nervous system, cervix, kidney, melanoma, prostate and upper gastrointestinal tract. Overall C-statistic for significant bleeding was 0.70, and 0.76 and 0.67 for major bleeding and for CRNMB-H, respectively.

CONCLUSIONS: This risk score may identify patients at risk of significant bleeding, while also helping to determine treatment duration.

PMID:37527782 | DOI:10.1055/a-2145-7238

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PubMed articles on: Cancer & VTE/PE

Genetic insights into resting heart rate and its role in cardiovascular disease

Nat Commun. 2023 Aug 2;14(1):4646. doi: 10.1038/s41467-023-39521-2.

ABSTRACT

Resting heart rate is associated with cardiovascular diseases and mortality in observational and Mendelian randomization studies. The aims of this study are to extend the number of resting heart rate associated genetic variants and to obtain further insights in resting heart rate biology and its clinical consequences. A genome-wide meta-analysis of 100 studies in up to 835,465 individuals reveals 493 independent genetic variants in 352 loci, including 68 genetic variants outside previously identified resting heart rate associated loci. We prioritize 670 genes and in silico annotations point to their enrichment in cardiomyocytes and provide insights in their ECG signature. Two-sample Mendelian randomization analyses indicate that higher genetically predicted resting heart rate increases risk of dilated cardiomyopathy, but decreases risk of developing atrial fibrillation, ischemic stroke, and cardio-embolic stroke. We do not find evidence for a linear or non-linear genetic association between resting heart rate and all-cause mortality in contrast to our previous Mendelian randomization study. Systematic alteration of key differences between the current and previous Mendelian randomization study indicates that the most likely cause of the discrepancy between these studies arises from false positive findings in previous one-sample MR analyses caused by weak-instrument bias at lower P-value thresholds. The results extend our understanding of resting heart rate biology and give additional insights in its role in cardiovascular disease development.

PMID:37532724 | PMC:PMC10397318 | DOI:10.1038/s41467-023-39521-2

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PubMed articles on: Cancer & VTE/PE

Intravascular Tumor Extension and Pulmonary Tumor Embolism in Children With Solid Malignancies: Is There a Role for Inferior Vena Cava Filters?

J Pediatr Hematol Oncol. 2023 Jul 27. doi: 10.1097/MPH.0000000000002731. Online ahead of print.

ABSTRACT

Intravascular tumor extension is an uncommon complication of solid malignancies that, when present in the inferior vena cava (IVC), can result in fatal pulmonary tumor embolism. Currently, neoadjuvant chemotherapy and surgery are the mainstays of treatment; however, there are no consensus guidelines for management. We describe three cases of pediatric solid malignancies with associated IVC extension and pulmonary tumor embolism. We hypothesize that there is scope for IVC filter placement in such cases to mitigate the risk of fatal pulmonary tumor embolism.

PMID:37526419 | DOI:10.1097/MPH.0000000000002731

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PubMed articles on: Cancer & VTE/PE

Comparative Efficacy of Direct Oral Anticoagulants and Low-Molecular-Weight Heparin in Cancer-Associated Thromboembolism: A Systematic Review and Meta-Analysis

Cureus. 2023 Jun 28;15(6):e41071. doi: 10.7759/cureus.41071. eCollection 2023 Jun.

ABSTRACT

Patients diagnosed with cancer often experience an abnormal occurrence of venous thromboembolism (VTE) and its related complications. In order to evaluate the safety and effectiveness of both treatment approaches, we conducted a comprehensive systematic review and meta-analysis within the realm of cancer-associated thromboembolism. A thorough search was conducted across PubMed, the Cochrane Library, and Embase databases to find studies comparing direct oral anticoagulants (DOACs) with low molecular weight heparins (LMWHs) for the treatment of VTE in patients with malignancy. The analyses utilized the random-effects model. This meta-analysis included 11 studies. The results showed that DOACs were associated with a significantly reduced risk of VTE recurrence (RR: 0.67; 95% CI: 0.55, 0.81, p<0.0001;<0.0001;

PMID:37519604 | PMC:PMC10375513 | DOI:10.7759/cureus.41071

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PubMed articles on: Cancer & VTE/PE

Tissue factor positive microparticles as a biomarker for increased risk of breast cancer-associated thrombosis: a mini review

Curr Opin Hematol. 2023 Sep 1;30(5):180-185. doi: 10.1097/MOH.0000000000000774.

ABSTRACT

PURPOSE OF REVIEW: Cancer-associated thrombosis (CAT), such as venous thromboembolism (VTE), is a frequent complication in cancer patients, resulting in poor prognosis. Breast cancer is not highly thrombogenic but is highly prevalent, resulting in increased VTE cases. Many cancers express tissue factor (TF), a glycoprotein that triggers coagulation. The cancer cells were shown to express and release substantial amounts of TF-positive microparticles (MPTF), associated with a prothrombotic state. This narrative review evaluated the current use of the procoagulant MPTF as a biomarker for thrombosis risk in breast cancer.

RECENT FINDINGS: Tumors of epithelial origin with elevated TF expression have been associated with increased VTE incidence. Thus, studies have affirmed the use of MPTF biomarkers for VTE risk in many cancers. Patients with metastatic breast cancer and CAT were found to exhibit elevated procoagulant microparticles in vitro, due to TF expression. The silencing of TF was associated with decreased microparticle release in breast carcinoma cell lines, associated with decreased coagulation.

SUMMARY: CAT is a multifactorial condition, with several various underlying diseases. It is proposed that MPTF may be an effective biomarker for thrombosis risk in breast cancer patients but requires a more systemic evaluation utilizing standardized quantification methods.

PMID:37522480 | DOI:10.1097/MOH.0000000000000774

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PubMed articles on: Cancer & VTE/PE

Clinical outcome of open ankle fractures in patients above 70 years of age

World J Orthop. 2023 Jul 18;14(7):554-561. doi: 10.5312/wjo.v14.i7.554. eCollection 2023 Jul 18.

ABSTRACT

BACKGROUND: Open fractures of the ankle are complex injuries requiring multidisciplinary input and are associated with significant morbidity and mortality. However, data on the clinical outcomes of open ankle fracture management in patients older than 70 is minimal.

AIM: To evaluate the clinical outcomes following open ankle fracture management in patients older than 70. Our secondary aim is to look at predictors of poor outcomes.

METHODS: Following local research and audit department registration, 22 years of prospectively collated data from an electronic database in a district general hospital were assessed. All patients older than 70 years of age with an open ankle fracture requiring surgical intervention were identified. Demographic information, the nature, and the number of surgical interventions were collated. Complications, including surgical site infection (SSI), venous thromboembolic events (VTEs) during hospital stay, and mortality rate, were reviewed.

RESULTS: A total of 37 patients were identified (median age: 84 years, range: 70-98); n= 30 females median age: 84 years, range: 70-97); n= 7 males median age: 74 years, range: 71-98)) who underwent surgical intervention after an open ankle fracture. Sixteen patients developed SSIs (43%). Superficial SSIs (n = 8) were managed without surgical intervention and treated with antibiotics and regular dressing changes. Deep SSIs (n = 8; 20%) required a median of 3 (range: 2-9) surgical interventions, with four patients requiring multiple washouts and one patient having metalwork removed. VTE incidence was 5% during the hospital stay. Eight patients died within 30 d, and mortality at one year was 19%. The 10-year mortality rate was 57%. The presence of a history of stroke, cancer, or prolonged inpatient stay was found to be predictive of lower survivorship in this population (log-rank test: cancer P= 0.008, stroke P= 0.001, length of stay > 33 d P= 0.015). The presence of a cardiac history was predictive of wound complications (logistic regression, P= 0.045). Age, number of operations, and diabetic history were found to be predictive of an increase in the length of stay (general linear model; age P< 0.001, number of operations P< 0.001, diabetes P= 0.041).

CONCLUSION: An open ankle fracture in a patient older than 70 years has at least a 20% chance of requiring repeated surgical intervention due to deep SSIs. The presence of a cardiac history appears to be the main predictor for wound complications.

PMID:37485433 | PMC:PMC10359747 | DOI:10.5312/wjo.v14.i7.554

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PubMed articles on: Cancer & VTE/PE

Using Machine Learning (ML) Models to Predict Risk of Venous Thromboembolism (VTE) Following Spine Surgery

Clin Spine Surg. 2023 Jul 24. doi: 10.1097/BSD.0000000000001498. Online ahead of print.