ABSTRACT

Cancer-associated thrombosis (CT), especially venous thromboembolism (VTE), is a common occurrence with several factors contributing to a wide diversity in thrombosis risk. The association between ABO blood groups and the risk for CT has been examined in various studies, with non-O blood type associated with an increased thrombosis risk; however, these studies have reported varying results with recognized limitations. ABO blood groups are known to be implicated in hemostasis, in an association mediated through von Willebrand factor (VWF). In this narrative review, we aim to summarize the current knowledge surrounding the role of ABO blood groups in VTE, with a particular focus on the role of VWF and other contributing risk factors on VTE occurrence. We found evidence from literature for the impact of ABO blood groups in determining the risk of VTE in healthy populations, with a limited number of studies examining this effect in cancer patients. Additionally, research on the impact of ABO on different cancer types lacks rigor, particularly in regard to other risk factors. Overall, most studies showed strong association of increased risk of VTE amongst cancer patients with non-O blood groups and increased VWF levels. This association was weaker in a few studies. Further research is needed before a solid conclusion can be made about the ABO or ABO-VWF-mediated hypercoagulability and VTE risk in various cancers. These studies will help determine if ABO typing can be an added biomarker to improve VTE risk assessment models in cancer patients.

PMID:37751774 | DOI:10.1055/s-0043-1775568

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PubMed articles on: Cancer & VTE/PE

A New Risk Prediction Model for Venous Thromboembolism and Death in Ambulatory Lung Cancer Patients

Cancers (Basel). 2023 Sep 15;15(18):4588. doi: 10.3390/cancers15184588.

ABSTRACT

(1) Background: Venous thromboembolism (VTE) is a frequent complication in ambulatory lung cancer patients during chemotherapy and is associated with increased mortality. (2) Methods: We analyzed 568 newly diagnosed metastatic lung cancer patients prospectively enrolled in the HYPERCAN study. Blood samples collected before chemotherapy were tested for thrombin generation (TG) and a panel of hemostatic biomarkers. The Khorana risk score (KRS), new-Vienna CATS, PROTECHT, and CONKO risk assessment models (RAMs) were applied. (3) Results: Within 6 months, the cumulative incidences of VTE and mortality were 12% and 29%, respectively. Patients with VTE showed significantly increased levels of D-dimer, FVIII, prothrombin fragment 1 + 2, and TG. D-dimer and ECOG performance status were identified as independent risk factors for VTE and mortality by multivariable analysis and utilized to generate a risk score that provided a cumulative incidence of VTE of 6% vs. 25%, death of 19% vs. 55%, and in the low- vs. high-risk group, respectively (p < 0.001). While all published RAMs significantly stratified patients for risk of death, only the CATS and CONKO were able to stratify patients for VTE. (4) Conclusions: A new prediction model was generated to stratify lung cancer patients for VTE and mortality risk, where other published RAMs failed.

PMID:37760562 | PMC:PMC10527104 | DOI:10.3390/cancers15184588

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PubMed articles on: Cancer & VTE/PE

A case of metastatic breast cancer complicated by pulmonary tumor thrombotic microangiopathy

Zhonghua Jie He He Hu Xi Za Zhi. 2023 Oct 12;46(10):1014-1018. doi: 10.3760/cma.j.cn112147-20230521-00253.

ABSTRACT

Pulmonary tumor thrombotic microangiopathy is a malignancy-related complication with rapid progression and high mortality. To improve the understanding of the disease, early diagnosis and treatment are key to successful treatment. A 39-year-old patient with pulmonary hypertension transferred from another hospital was admitted to the First Affiliated Hospital of Guangzhou Medical University on September 26, 2021. The patient developed shortness of breath and progressive exacerbation over the past month. No pulmonary artery embolism was seen on computed tomography pulmonary angiography (CTPA) at the outside hospital where the breast cancer was diagnosed. Pulmonary tumor thrombotic microangiopathy was immediately considered on admission and oncological endocrine therapy was started. After treatment, the patient's dyspnoea improved, PET-CT showed significant tumor regression, and cardiac ultrasound showed a significant decrease in pulmonary artery pressure. The successful treatment experience of this case was summarized for reference.

PMID:37752045 | DOI:10.3760/cma.j.cn112147-20230521-00253

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PubMed articles on: Cancer & VTE/PE

Venous Thromboembolism Chemoprophylaxis Adherence Rates After Major Cancer Surgery

JAMA Netw Open. 2023 Sep 5;6(9):e2335311. doi: 10.1001/jamanetworkopen.2023.35311.

ABSTRACT

IMPORTANCE: Venous thromboembolism (VTE) represents a major source of preventable morbidity and mortality and is a leading cause of death in the US after cancer surgery. Previous research demonstrated variability in VTE chemoprophylaxis prescribing, although it is unknown how these rates compare with performance in the Veterans Health Administration (VHA).

OBJECTIVE: To determine VTE rates after cancer surgery, as well as rates of inpatient and outpatient (posthospital discharge) chemoprophylaxis adherence within the VHA.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study within 101 hospitals of the VHA health system included patients aged 41 years or older without preexisting bleeding disorders or anticoagulation usage who underwent surgical treatment for cancer with general surgery, thoracic surgery, or urology between January 1, 2015, and December 31, 2022. The VHA Corporate Data Warehouse, Pharmacy Benefits Management database, and the Veterans Affairs Surgical Quality Improvement Program database were used to identify eligible patients. Data analysis was conducted between January 2022 and July 2023.

EXPOSURES: Inpatient surgery for cancer with general surgery, thoracic surgery, or urology.

MAIN OUTCOMES AND MEASURES: Rates of postoperative VTE events within 30 days of surgery and VTE chemoprophylaxis adherence were determined. Multivariable Poisson regression was used to determine incidence-rate ratios of inpatient and postdischarge chemoprophylaxis adherence by surgical specialty.

RESULTS: Overall, 30 039 veterans (median [IQR] age, 67 [62-71] years; 29 386 men [97.8%]; 7771 African American or Black patients [25.9%]) who underwent surgery for cancer and were at highest risk for VTE were included. The overall postoperative VTE rate was 1.3% (385 patients) with 199 patients (0.7%) receiving a diagnosis during inpatient hospitalization and 186 patients (0.6%) receiving a diagnosis postdischarge. Inpatient chemoprophylaxis was ordered for 24 139 patients (80.4%). Inpatient chemoprophylaxis ordering rates were highest for patients who underwent procedures with general surgery (10 102 of 10 301 patients [98.1%]) and lowest for patients who underwent procedures with urology (11 471 of 17 089 patients [67.1%]). Overall, 3142 patients (10.5%) received postdischarge chemoprophylaxis, with notable variation by specialty.

CONCLUSIONS AND RELEVANCE: These findings indicate the overall VTE rate after cancer surgery within the VHA is low, VHA inpatient chemoprophylaxis rates are high, and postdischarge VTE chemoprophylaxis prescribing is similar to that of non-VHA health systems. Specialty and procedure variation exists for chemoprophylaxis and may be justified given the low risks of overall and postdischarge VTE.

PMID:37768664 | PMC:PMC10539988 | DOI:10.1001/jamanetworkopen.2023.35311

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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

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PubMed articles on: Cancer & VTE/PE

Extended Venous Thromboembolism Prophylaxis after Robotic Staging for Endometrial Cancer

South Med J. 2023 Oct;116(10):790-794. doi: 10.14423/SMJ.0000000000001611.

ABSTRACT

OBJECTIVES: Our objectives were to estimate the incidence of venous thromboembolism (VTE) after robotic staging for endometrial cancer and to compare the incidence of VTE in patients who received a single dose of preoperative prophylaxis of enoxaparin with those who received extended postoperative prophylaxis.

METHODS: This study is a retrospective chart review of patients who underwent robot-assisted surgical staging for endometrial cancer. Patients were categorized into two groups: preoperative prophylaxis (PP), patients who received a single dose of enoxaparin preoperatively, and extended prophylaxis (EP), patients who received 28 days of enoxaparin postoperatively.

RESULTS: In total, 148 patients were included, with 117 patients in the PP group and 31 patients in the EP group. The overall incidence of VTE within 30 days postoperatively was 0.67%. No significant difference was found between the PP and the EP groups (0.9% and 0%, respectively; P = 1.00). Most patients in the cohort had endometrioid adenocarcinoma (78%) with low-grade disease (70%), although there were a greater number of patients in the PP group with uterine serous carcinoma compared with the EP group (17% vs 10%; P = 0.034). The PP group had higher estimated blood loss (106 vs 81 mL; P = 0.009) and longer operative times (178 vs 151 min; P = 0.028) compared with the EP group. Significantly more patients in the PP group underwent lymph node dissection compared with the EP group (32% vs 7%; P = 0.008).

CONCLUSIONS: The incidence of VTE following robot-assisted surgical staging for endometrial cancer in this study was 0.67%. No significant difference was found in VTE incidence between the PP group compared with the EP group. Mechanical prophylaxis plus a single dose of preoperative pharmacologic prophylaxis may suffice for low-risk patients following robotic surgical staging for endometrial cancer.

PMID:37788812 | DOI:10.14423/SMJ.0000000000001611

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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.

ABSTRACT

PURPOSE: The risk of thromboembolic disease is high in patients with lung transplantation and is associated with significant morbidity and mortality with single healthy transplanted lung. We present a case involving successful endovascular management of life-threatening acute massive pulmonary embolism (PE) in a patient with single lung transplant and atrial septal defect (ASD).

CASE REPORT: A 65-year-old man with a history of interstitial lung disease status post single left orthotopic lung transplant in 2012 presented with acute massive PE and clot burden in the pulmonary arteries of the transplanted left lung. Severe right heart dysfunction, hemodynamic instability, and requirement for vasopressors persisted post systemic thrombolytic therapy. As a result, the patient underwent successful endovascular mechanical thrombectomy with immediate improvement in oxygen saturation and hemodynamic status. The procedure was performed without adverse outcomes or paradoxical embolization despite the presence of ASD. The right heart dysfunction resolved, the patient was extubated the next day, and was discharged to home 2 days post procedure.

CONCLUSIONS: Endovascular mechanical thrombectomy was safely used to treat acute massive PE in a single transplanted lung in the presence of ASD.

CLINICAL IMPACT: Endovascular mechanical thrombectomy could be safely utilized to treat patients with lung transplant and acute massive or submassive pulmonary embolism. However, safely of mechanical thrombectomy should be determined in case-based scenarios and based on time interval from transplantation to when the thrombectomy is required.

PMID:37776207 | DOI:10.1177/15266028231201357

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PubMed articles on: Cancer & VTE/PE

Hypoxia-induced exosomes facilitate lung pre-metastatic niche formation in hepatocellular carcinoma through the miR-4508-RFX1-IL17A-p38 MAPK-NF-κB pathway

Int J Biol Sci. 2023 Sep 4;19(15):4744-4762. doi: 10.7150/ijbs.86767. eCollection 2023.

ABSTRACT

Background: Hypoxia plays an important role in the lung metastasis of hepatocellular carcinoma (HCC). However, the process by which hypoxia promotes the formation of a pre-metastatic niche (PMN) and its underlying mechanism remain unclear. Methods: Exosomes derived from normoxic and hypoxic HCC cells were collected to induce fibroblast activation in vitro and PMN formation in vivo. The micro RNA (miR) profiles of the exosomes were sequenced to identify differentially expressed miRNAs. Gain- and loss-of-function analyses were performed to investigate miR-4508 function. Dual-luciferase, western blotting, and real-time reverse transcription-PCR analyses were used to identify the direct targets of miR-4508 and its downstream signaling pathways. To demonstrate the roles of hypoxic tumor-derived exosomes (H-TDEs) and miR-4508 in the lung metastasis of liver cancer, H22 tumor cells were injected through the tail vein of mice. Blood plasma-derived exosomes from patients with HCC who underwent transarterial chemoembolization (TACE) were applied to determine clinical correlations. Results: We demonstrated that H-TDEs activated lung fibroblasts and facilitated PMN formation, thereby promoting lung metastasis in mice. Screening for upregulated exosomal miRNAs revealed that miR-4508 and its target, regulatory factor X1 (RFX1), were involved in H-TDE-induced lung PMN formation. Moreover, miR-4508 was significantly upregulated in plasma exosomes derived from patients with HCC after TACE. We confirmed that the p38 MAPK-NF-κB signaling pathway is involved in RFX1 knockdown-induced fibroblast activation and PMN formation. In addition, IL17A, a downstream target of RFX1, was identified as a link between RFX1 knockdown and p38 MAPK activation in fibroblasts. Conclusion: Hypoxia enhances the release of TDEs enriched with miR-4508, thereby promoting lung PMN formation by targeting the RFX1-IL17A-p38 MAPK-NF-κB pathway. These findings highlight a novel mechanism underlying hypoxia-induced pulmonary metastasis of HCC.

PMID:37781522 | PMC:PMC10539707 | DOI:10.7150/ijbs.86767

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PubMed articles on: Cancer & VTE/PE

Machine-Learning-Assisted Procoagulant Extracellular Vesicle Barcode Assay toward High-Performance Evaluation of Thrombosis-Induced Death Risk in Cancer Patients

ACS Nano. 2023 Oct 4. doi: 10.1021/acsnano.3c04615. Online ahead of print.

ABSTRACT

Venous thromboembolism (VTE) is the most fatal complication in cancer patients. Unfortunately, the frequent misdiagnosis of VTE owing to the lack of accurate and efficient evaluation approaches may cause belated medical intervention and even sudden death. Herein, we present a rapid, easily operable, highly specific, and highly sensitive procoagulant extracellular vesicle barcode (PEVB) assay composed of TiO2 nanoflower (TiNFs) for visually evaluating VTE risk in cancer patients. TiNFs demonstrate rapid label-free EV capture capability by the synergetic effect of TiO2-phospholipids molecular interactions and topological interactions between TiNFs and EVs. From ordinary plasma samples, the PEVB assay can evaluate potential VTE risk by integrating TiNFs-based EV capture and in situ EV procoagulant ability test with machine-learning-assisted clinical data analysis. We demonstrate the feasibility of this PEVB assay in VTE risk evaluation by screening 167 cancer patients, as well as the high specificity (97.1%) and high sensitivity (96.8%), fully exceeding the nonspecific and posterior traditional VTE test. Together, we proposed a TiNFs platform allowing for highly accurate and timely diagnosis of VTE in cancer patients.

PMID:37791763 | DOI:10.1021/acsnano.3c04615

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PubMed articles on: Cancer & VTE/PE

The Role of Injectables in the Treatment and Prevention of Cancer-Associated Thrombosis

Cancers (Basel). 2023 Sep 20;15(18):4640. doi: 10.3390/cancers15184640.

ABSTRACT

Cancer-associated thrombosis (CAT) is a leading cause of death among patients with cancer. CAT can manifest itself as venous thromboembolism (VTE), in the form of deep vein thrombosis or pulmonary embolism, or arterial thromboembolism. The pathophysiology of CAT is complex and depends on cancer-, patient-, treatment- and biomarkers-related factors. Treatment of VTE in patients with cancer is complex and includes three major classes of anticoagulant agents: heparin and its derivatives, e.g., low molecular weight heparins, direct oral anticoagulants (DOACs), and vitamin K inhibitors. Given the tremendous heterogeneity of clinical situations in patients with cancer and the challenges of CAT, there is no single universal treatment option for patients suffering from or at risk of CAT. Initial studies suggested that patients seemed to prefer an anticoagulant that would not interfere with their cancer treatment, suggesting the primacy of cancer over VTE, and favoring efficacy and safety over convenience of route of administration. Recent studies show that when the efficacy and safety aspects are similar, patients prefer the oral route of administration. Despite this, injectables are a valid option for many patients with cancer.

PMID:37760609 | PMC:PMC10526875 | DOI:10.3390/cancers15184640

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PubMed articles on: Cancer & VTE/PE

Anti-Inflammatory and Anticancer Effects of Anticoagulant Therapy in Patients with Malignancy

Life (Basel). 2023 Sep 10;13(9):1888. doi: 10.3390/life13091888.