ABSTRACT

BACKGROUND: The way in which to prevent recurrent venous thromboembolism (VTE) is an unmet clinical need in cancer patients. International guidelines only provide conditional recommendations and do not specify which anticoagulant and dose should be used. In the last 2 years, we have been using low-dose rivaroxaban to prevent VTE recurrences in cancer patients. The results of this real-life experience are presented in this study.

METHODS: All patients had cancer and had previously completed a cycle of at least six months of full-dose anticoagulation for the treatment of a VTE index event, before receiving a prescription of low-dose rivaroxaban (10 mg once daily) for secondary prevention of VTE. Effectiveness and safety of this therapeutic regimen were evaluated in terms of VTE recurrences, major bleedings (MB), and clinically relevant non-major bleedings (CRNMB).

RESULTS: The analysis included 106 cancer patients. Their median age was 60 years (IQR 50-69). Metastatic cancer was present in 87 patients (82.1%). Six patients (5.7%) had brain metastases. Over a median follow-up time of 333 days (IQR 156-484), the incidence of VTE recurrences was 3.8% (95%CI 1.0-9.4), with a recurrence rate of 4.0 per 100 person-years (95%CI 1.1-10.2). We observed no MB (0.0%) and three CRNMB (2.8%) (95%CI 0.6-8.1).

CONCLUSIONS: Low-dose rivaroxaban is potentially effective and safe in cancer patients that require prevention of recurrent VTE. Large-scale studies are needed to confirm these findings.

PMID:37835070 | PMC:PMC10573527 | DOI:10.3390/jcm12196427

04:23

PubMed articles on: Cancer & VTE/PE

Inhibition of Factor XI: A New Era in the Treatment of Venous Thromboembolism in Cancer Patients?

Int J Mol Sci. 2023 Sep 22;24(19):14433. doi: 10.3390/ijms241914433.

ABSTRACT

Direct oral anticoagulants against activated factor X and thrombin were the last milestone in thrombosis treatment. Step by step, they replaced antivitamin K and heparins in most of their therapeutic indications. As effective as the previous anticoagulant, the decreased but persistent risk of bleeding while using direct oral anticoagulants has created space for new therapeutics aiming to provide the same efficacy with better safety. On this basis, drug targeting factor XI emerged as an option. In particular, cancer patients might be one of the populations that will most benefit from this technical advance. In this review, after a brief presentation of the different factor IX inhibitors, we explore the potential benefit of this new treatment for cancer patients.

PMID:37833881 | PMC:PMC10572808 | DOI:10.3390/ijms241914433

04:23

PubMed articles on: Cancer & VTE/PE

Enoxaparin for the long-term therapy of venous thromboembolism in patients with cancer and renal insufficiency

Thromb Haemost. 2023 Oct 13. doi: 10.1055/a-2191-7510. Online ahead of print.

ABSTRACT

BACKGROUND: The optimal therapy of venous thromboembolism (VTE) in cancer patients with renal insufficiency (RI) is unknown. Current guidelines recommend to use low-molecular-weight heparin over direct oral anticoagulants to treat VTE in cancer patients at high-risk for bleeding.

METHODS: We used the RIETE registry to compare the 6-month incidence rates of: 1) VTE recurrences vs. major bleeding; and 2) fatal pulmonary embolism (PE) vs. fatal bleeding in 3 subgroups (those with mild, moderate, or severe RI) of cancer patients receiving enoxaparin monotherapy.

RESULTS: From January 2009 through June 2022, 2,844 patients with RI received enoxaparin for ≥6 months: 1,432 (50%) had mild, 1,168 (41%) moderate, and 244 (8.6%) had severe RI. Overall, 68%, 62% and 12% respectively, received the recommended doses. Among patients with mild RI, the rates of VTE recurrences vs. major bleeding (4.6% vs. 5.4%) and fatal PE vs. fatal bleeding (1.3% vs. 1.2%) were similar. Among patients with moderate RI, VTE recurrences were half as common as major bleeding (3.1% vs. 6.3%), but fatal PE and fatal bleeding were close (1.8% vs. 1.2%). Among patients with severe RI, VTE recurrences were 3-fold less common than major bleeding (4.1% vs. 13%), but fatal PE was 3-fold more frequent than fatal bleeding (2.5% vs. 0.8%). During the first 10 days, fatal PE was 5-fold more common than fatal bleeding (2.1% vs. 0.4%).

CONCLUSIONS: Among cancer patients with severe RI, fatal PE was 5-fold more common than fatal bleeding. The recommended doses of enoxaparin in these patients should be revisited.

PMID:37832588 | DOI:10.1055/a-2191-7510

04:24

PubMed articles on: Cancer & VTE/PE

Implementation of routine venous thromboembolism prophylaxis during neoadjuvant chemotherapy for patients with ovarian cancer

Gynecol Oncol. 2023 Oct 11;178:89-95. doi: 10.1016/j.ygyno.2023.10.001. Online ahead of print.

ABSTRACT

OBJECTIVE: To compare the venous thromboembolism (VTE) rate in patients with ovarian cancer undergoing neoadjuvant chemotherapy before and after implementing routine thromboprophylaxis.

METHODS: This is a quasi-experimental pre-post study evaluating the VTE rate in patients with ovarian cancer who received neoadjuvant chemotherapy following a quality improvement initiative of routine thromboprophylaxis within a single healthcare system that started in January 2017. Patients were excluded if VTE was diagnosed before initiating chemotherapy. Patient factors and perioperative variables of interest were investigated for their association with VTE through univariate and multivariate models.

RESULTS: Of the 136 patients in the pre-implementation group, 3.7% (n = 5) received thromboprophylaxis. Of the 154 patients in the post-implementation group, 65.6% (n = 101) received thromboprophylaxis. Provider compliance varied from 51% in 2019 to 79.3% in 2021. The overall rate of VTE, from the start of chemotherapy to the end of treatment, was 21.3% (n = 29) pre- and 8.4% (n = 13) in the post-implementation group (p < 0.01). There was no difference in major bleeding events between groups (0% vs. 0.68%, p = 0.63). On univariate analysis, thromboprophylaxis (OR 0.19; 95% CI 0.07-0.52) and post-implementation period (OR 0.34; 95% CI 0.17-0.69) were associated with a decreased risk of any VTE during primary treatment. On multivariate analysis, only thromboprophylaxis remained significantly associated with reduced VTE rates (aOR 0.19; 95% CI 0.07-0.53).

CONCLUSION: Routine thromboprophylaxis during neoadjuvant chemotherapy is associated with reduced risk of VTE throughout primary treatment and is not associated with increased bleeding events.

PMID:37832182 | DOI:10.1016/j.ygyno.2023.10.001

04:24

PubMed articles on: Cancer & VTE/PE

Risk of Thrombosis and Bleeding in Gynecologic Cancer Surgery: Systematic Review and Meta-Analysis

Am J Obstet Gynecol. 2023 Oct 10:S0002-9378(23)00735-4. doi: 10.1016/j.ajog.2023.10.006. Online ahead of print.

ABSTRACT

OBJECTIVE: To provide procedure-specific estimates of the risk of symptomatic venous thromboembolism (VTE) and major bleeding, in the absence of thromboprophylaxis, following gynecologic cancer surgery.

DATA SOURCES: We conducted comprehensive searches on Embase, MEDLINE, Web of Science, and Google Scholar for observational studies. We also reviewed reference lists of eligible studies and review articles. We performed separate searches for randomized trials addressing effects of thromboprophylaxis and conducted a web-based survey on thromboprophylaxis practice.

STUDY ELIGIBILITY CRITERIA: Observational studies enrolling ≥50 adult patients undergoing gynecologic cancer surgery procedures reporting absolute incidence for at least one of the following: symptomatic pulmonary embolism, symptomatic deep vein thrombosis, symptomatic VTE, bleeding requiring reintervention (including re-exploration and angioembolization), bleeding leading to transfusion or post-operative hemoglobin <70

STUDY APPRAISAL AND SYNTHESIS METHODS: Two reviewers independently assessed eligibility, performed data extraction, and evaluated risk of bias of eligible articles. We adjusted the reported estimates for thromboprophylaxis and length of follow-up and used the median value from studies to determine cumulative incidence at 4 weeks post-surgery stratified by patient VTE risk factors, and used the GRADE approach to rate evidence certainty.

RESULTS: We included 188 studies (398,167 patients) reporting on 37 gynecologic cancer surgery procedures. The evidence certainty was generally low to very low. Median symptomatic VTE risk (in the absence of prophylaxis) was <1%2.0% in 13 of 37 (35%). The risks of VTE varied from 0.1% in low VTE risk patients undergoing cervical conization to 33.5% in high VTE risk patients undergoing pelvic exenteration. Estimates of bleeding requiring reintervention varied from <0.1%<1%

CONCLUSIONS: VTE reduction with thromboprophylaxis likely outweighs increase in bleeding requiring reintervention in many gynecologic cancer procedures (e.g., open surgery for ovarian cancer and pelvic exenteration). In some procedures (e.g., laparoscopic total hysterectomy without lymphadenectomy), thromboembolism and bleeding risks are similar, and decisions depend on individual risk prediction and values and preferences regarding VTE and bleeding.

PMID:37827272 | DOI:10.1016/j.ajog.2023.10.006

04:24

PubMed articles on: Cancer & VTE/PE

Accuracy of the ACS NSQIP Surgical Risk Calculator for Predicting Postoperative Complications in Gastric Cancer Following Open Gastrectomy

Am Surg. 2023 Oct 12:31348231206581. doi: 10.1177/00031348231206581. Online ahead of print.

ABSTRACT

INTRODUCTION: The prediction of complications before gastric surgery is of utmost importance in shared decision making and proper counseling of the patient in order to minimize postoperative complications. Our aim was to evaluate the predictive validity of American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) risk calculator in gastric cancer patients who underwent gastrectomy.

METHODS: Preoperative assessment data of 432 patients were retrospectively reviewed and manually entered into the calculator. The accuracy of the calculator was evaluated using Pearson's chi-squared test, C-statistic, Brier score, and Hosmer-Lemeshow test.

RESULTS: The lowest Brier scores were observed in urinary tract infection, renal failure, venous thromboembolism, pneumonia, and cardiac complications. Best results were obtained for predicting sepsis, discharge to rehabilitation facility, and death (low Brier scores, C-statistic >.7, and Hosmer-Lemeshow P > .05).

CONCLUSION: The calculator had a strong performance in predicting sepsis, discharge to the rehabilitation facility, and death. However, it performed poor in predicting the most commonly observed events (any or serious complication and surgical site infection).

PMID:37823864 | DOI:10.1177/00031348231206581

04:24

PubMed articles on: Cancer & VTE/PE

Venous thromboembolism prevention in cancer care: implementation strategies to address underuse

Res Pract Thromb Haemost. 2023 Aug 20;7(7):102173. doi: 10.1016/j.rpth.2023.102173. eCollection 2023 Oct.

ABSTRACT

BACKGROUND: Evidenced-based interventions have been developed to prevent venous thromboembolism (VTE) in ambulatory patients with cancer, including VTE-risk assessment for all patients and targeted primary thromboprophylaxis for high-risk patients. Despite supportive evidence and recommendations, oncologists rarely assess VTE risk or provide primary prophylaxis. Our previous work identified barriers and facilitators to using VTE prevention interventions in oncology practice.

OBJECTIVES: To identify potential strategies that address the identified barriers and leverage facilitators to achieve successful implementation of evidence-based interventions for VTE prevention in oncology practice.

METHODS: We used the Implementation Research Logic Model, an implementation science framework, to map the relationships among barriers and facilitators, feasible and effective implementation strategies, and implementation and clinical outcomes that will be used to evaluate the implementation strategies.

RESULTS: We identified 12 discrete implementation strategies (eg, conducting clinician education and training and staged implementation scale-up) that address barriers and leverage facilitators through their mechanisms of action (eg, increased clinician awareness of evidence and targeting the highest effectiveness). We identified key implementation (eg, penetration, adoption, acceptability, fidelity, appropriateness, and sustainability), system (eg, integration of VTE-risk assessment into clinical workflow), and clinical (eg, lower VTE rates) outcomes targeted by the selected strategies.

CONCLUSION: Using the Implementation Research Logic Model framework and building on our knowledge of barriers and facilitators, we identified implementation strategies and important outcomes to evaluate these strategies. We will use these results to test and measure the strategies to improve the uptake of evidence-based recommendations for VTE prevention in oncology practice.

PMID:37822563 | PMC:PMC10562910 | DOI:10.1016/j.rpth.2023.102173

04:24

PubMed articles on: Cancer & VTE/PE

Tissue factor pathway inhibitor is associated with risk of venous thromboembolism and all-cause mortality in patients with cancer

Haematologica. 2023 Oct 12. doi: 10.3324/haematol.2023.283581. Online ahead of print.

ABSTRACT

Venous thromboembolism (VTE) is a common complication in patients with cancer. Data on the role of natural inhibitors of coagulation for occurrence of cancerassociated VTE are limited, thus, we investigated the association of tissue factor pathway inhibitor (TFPI) with risk of VTE and all-cause mortality in patients with cancer. Total TFPI antigen levels were measured with a commercially available ELISA in patients included in the Vienna Cancer and Thrombosis Study, a prospective observational cohort study with the primary outcome VTE. Competing risk analysis and Cox regression analysis were performed to explore the association of TFPI levels with VTE and all-cause mortality. TFPI was analyzed in 898 patients (median age: 62 years [interquartile range, IQR: 53-68]; 407 [45%] women). Sixtyseven patients developed VTE and 387 died (24-month cumulative risk: 7.5% and 42.1%, respectively). Patients had median TFPI levels at study inclusion of 56.4ng/mL (IQR: 45.7-70.0), with highest levels in tumor types known to have a high risk of VTE (gastroesophageal-, pancreatic and brain-cancer: 62.0ng/mL [IQR: 52.0-75.0]). In multivariable analysis adjusting for age, sex, cancer type and stage, TFPI levels were associated with VTE risk (SHR per doubling: 1.63, 95%CI: 1.03-2.57). When patients with high and intermediate/low VTE risk were analyzed separately, the association remained independently associated in the high risk group only (SHR: 2.63, 95%CI: 1.40-4.94). TFPI levels were independently associated with all-cause mortality (HR: 2.36, 95%CI: 1.85-3.00). In cancer patients increased TFPI levels are associated with VTE risk, specifically in patients with high risk tumor types, and with all-cause mortality.

PMID:37822244 | DOI:10.3324/haematol.2023.283581

04:24

PubMed articles on: Cancer & VTE/PE

Obstructive Sleep Apnea and Venous Thromboembolism: Unraveling the Emerging Association

Cureus. 2023 Aug 30;15(8):e44367. doi: 10.7759/cureus.44367. eCollection 2023 Aug.

ABSTRACT

Oxidative stress has emerged as a significant contributor to skeletal muscle atrophy, influencing cellular processes that underlie muscle wasting. This review article delves into the intricate interplay between oxidative stress and muscle atrophy, shedding light on its mechanisms and implications. We begin by outlining the fundamental concepts of oxidative stress, delineating reactive oxygen species (ROS) and reactive nitrogen species (RNS), their sources, and the ensuing oxidative damage to cellular components. Subsequently, we delve into skeletal muscle atrophy, elucidating its diverse forms, molecular pathways, key signaling cascades, and the role of inflammation in exacerbating muscle wasting. Bridging these concepts, we explore the connections between oxidative stress and muscle atrophy, unveiling how oxidative stress impacts muscle protein synthesis and breakdown, perturbs cellular signaling pathways, and contributes to mitochondrial dysfunction. The review underscores the complexity of quantifying and interpreting oxidative stress markers, highlighting the challenges posed by the dynamic nature of oxidative stress and the presence of basal ROS levels. Addressing the specificity of oxidative stress markers, we emphasize the importance of selecting markers pertinent to muscle tissue and considering systemic influences. Standardization of experimental protocols emerges as a critical need to ensure consistency and reproducibility across studies. Looking ahead, we discuss the implications of oxidative stress in diverse scenarios, encompassing age-related muscle loss (sarcopenia), muscle wasting in chronic diseases like cancer cachexia, and disuse-induced muscle atrophy. Additionally, we delve into potential therapeutic strategies, including antioxidant supplementation, exercise, pharmacological interventions, nutritional approaches, and lifestyle modifications, as avenues to mitigate oxidative stress-driven muscle atrophy. The review concludes by outlining promising future directions in this field, calling for deeper exploration of specific oxidative stress markers, understanding the temporal dynamics of oxidative stress, validation through translational studies in humans, and the development of targeted therapeutic interventions. By advancing our understanding of the intricate relationship between oxidative stress and skeletal muscle atrophy, this review contributes to paving the way for innovative strategies to address muscle wasting and improve muscle health.

PMID:37779809 | PMC:PMC10540504 | DOI:10.7759/cureus.44367

04:24

PubMed articles on: Cancer & VTE/PE

Anticoagulation for the treatment of septic cerebral venous sinus thrombosis in the setting of pediatric sinogenic and otogenic intracranial infections

Neurosurg Focus. 2023 Oct;55(4):E8. doi: 10.3171/2023.7.FOCUS23374.

ABSTRACT

OBJECTIVE: Septic cerebral venous sinus thrombosis (CVST) is a recognized complication of pediatric sinogenic and otogenic intracranial infections. The optimal treatment paradigm remains controversial. Proponents of anticoagulation highlight its role in preventing thrombus propagation and promoting recanalization, while others cite the risk of hemorrhagic complications, especially after a neurosurgical procedure for an epidural abscess or subdural empyema. Here, the authors investigated the diagnosis, management, and outcomes of pediatric patients with sinogenic or otogenic intracranial infections and a septic CVST.

METHODS: All patients 21 years of age or younger, who presented with an intracranial infection in the setting of sinusitis or otitis media and who underwent neurosurgical treatment at Connecticut Children's, Rady Children's Hospital-San Diego, or Ann and Robert H. Lurie Children's Hospital of Chicago from March 2015 to March 2023, were retrospectively reviewed. Demographic, clinical, and radiological data were systematically collated.

RESULTS: Ninety-six patients were treated for sinusitis-related and/or otitis media-related intracranial infections during the study period, 15 (15.6%) of whom were diagnosed with a CVST. Of the 60 patients who presented prior to the COVID-19 pandemic, 6 (10.0%) were diagnosed with a septic CVST, whereas of the 36 who presented during the COVID-19 pandemic, 9 (25.0%) had a septic CVST (p = 0.050). The superior sagittal sinus was involved in 12 (80.0%) patients and the transverse and/or sigmoid sinuses in 4 (26.7%). Only 1 (6.7%) patient had a fully occlusive thrombus. Of the 15 patients with a septic CVST, 11 (73.3%) were initiated on anticoagulation at a median interval of 4 (IQR 3-5) days from the most recent neurosurgical procedure. Five (45.5%) patients who underwent anticoagulation demonstrated complete recanalization on follow-up imaging, and 4 (36.4%) had partial recanalization. Three (75.0%) patients who did not undergo anticoagulation demonstrated complete recanalization, and 1 (25.0%) had partial recanalization. None of the patients treated with anticoagulation experienced hemorrhagic complications.

CONCLUSIONS: Septic CVST is frequently identified among pediatric patients undergoing neurosurgical intervention for sinogenic and/or otogenic intracranial infections and may have become more prevalent during the COVID-19 pandemic. Anticoagulation can be used safely in the acute postoperative period if administered cautiously, in a monitored setting, and with interval cross-sectional imaging. However, some patients exhibit excellent outcomes without anticoagulation, and further studies are needed to identify those who may benefit the most from anticoagulation.

PMID:37778041 | DOI:10.3171/2023.7.FOCUS23374

04:24

PubMed articles on: Cancer & VTE/PE

The Role of Mechanical Thrombectomy for Acute Massive Pulmonary Embolism in a Patient With Unilateral Lung Transplant and Atrial Septal Defect

J Endovasc Ther. 2023 Sep 30:15266028231201357. doi: 10.1177/15266028231201357. Online ahead of print.