topics

2/19/26

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

The Impact of Type 2 Myocardial Infarction in Acute Pancreatitis: Analysis of 1.1 Million Hospitalizations and Review of the Literature

Cureus. 2023 Aug 25;15(8):e44113. doi: 10.7759/cureus.44113. eCollection 2023 Aug.

ABSTRACT

Introduction Acute pancreatitis (AP) is a common inflammatory disorder with acute onset and rapid progression. Studies have reported cardiac injury in patients with AP. It is often thought that stress cardiomyopathy can induce these changes leading to type 2 myocardial infarction (type 2 MI) in AP. Our study aims to assess the prevalence as well as the impact of type 2 MI on outcomes in patients with AP. Methods National Inpatient Sample (NIS) 2016-2020 was used to identify adult patients (age>18) with acute pancreatitis. We excluded patients with STEMI, NSTEMI, pancreatic cancer, or chronic pancreatitis. Patients with missing demographics and mortality were also excluded. Patients were stratified into two groups, based on the presence of type 2 MI. Multivariate logistic regression analysis was performed to assess the impact of concomitant type 2 MI on mortality, sepsis, acute kidney injury (AKI), ICU admission, deep venous thrombosis (DVT), and pulmonary embolism (PE) after adjusting for patient demographics, hospital characteristics, etiology of AP and the Elixhauser comorbidities. Results Of the 1.1 million patients in the study population, only 2315 patients had type 2 MI. The majority of the patients in the type 2 MI group were aged >65 years (49.2%, p<0.001),<0.001),<0.001),<0.001),<0.001),<0.001)<0.001).<0.001).<0.001)<0.001).

PMID:37750110 | PMC:PMC10518190 | DOI:10.7759/cureus.44113

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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

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PubMed articles on: Cardio-Oncology

Hormone therapy, cardio-metabolic profile, and cardiotoxicity. Still a dark side of cardio-oncology - Part 2: Prostate cancer

G Ital Cardiol (Rome). 2023 Oct;24(10):781-791. doi: 10.1714/4100.40978.

ABSTRACT

Hormone therapies (HTs) with anti-androgenic properties are a cornerstone for the treatment of prostate cancer (PC) and have significantly improved the survival of patients, though exposing them to a higher risk of cardiovascular diseases (CVDs), which represent a major cause of morbidity and mortality. This occurs due to the high average age of patients undergoing HT for PC, an age group in which CVDs have a high prevalence and incidence, and due to the type and duration of HTs that are increasingly effective but at the same time more aggressive towards cardiovascular health. Recent evidence from the real world suggests, however, that the cardiometabolic risk is widely underestimated and undertreated with significant impact also on the oncological prognosis. In the light of the results of the PRONOUNCE study, in this review it is emphasized the need for a multidisciplinary management of patients with PC who are candidate for or treated with HT by implementing a personalized treatment program in accordance with the current European guidelines on CVD prevention.

PMID:37767830 | DOI:10.1714/4100.40978

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PubMed articles on: Cardio-Oncology

In-hospital outcomes after acute myocardial infarction with obstructive coronary artery disease in critically ill patients hospitalized for non-cardiac disease

Ann Intensive Care. 2023 Sep 19;13(1):87. doi: 10.1186/s13613-023-01188-9.

ABSTRACT

OBJECTIVE: This systematic review and meta-analysis compares the rate of venous thromboembolism (VTE) in surgical inpatients with pharmacological thromboprophylaxis and additional graduated compression stockings (GCS) versus pharmacological thromboprophylaxis alone.

SUMMARY BACKGROUND DATA: Surgical inpatients have elevated VTE risk; recent studies cast doubt whether GCS confer additional protection against VTE, compared to pharmacological thromboprophylaxis alone.

METHODS: The review followed PRISMA guidelines using a registered protocol (CRD42017062655). The MEDLINE and Embase databases were searched to November 2022. Randomised trials reporting VTE rate after surgical procedures, utilising pharmacological thromboprophylaxis, with or without GCS, were included. The rates of deep venous thrombosis (DVT), pulmonary embolism (PE), VTE-related mortality were pooled via fixed and random effects.

RESULTS: In head-to-head meta-analysis, the risk of DVT for GCS and pharmacological thromboprophylaxis was 0.85 (95% CI 0.54-1.36) versus for pharmacological thromboprophylaxis alone (2 studies, 70 events, 2653 participants). The risk of DVT in pooled trial arms for GCS and pharmacological thromboprophylaxis was 0.54 (95% CI 0.23-1.25) versus pharmacological thromboprophylaxis alone (33 trial arms, 1228 events, 14,108 participants). The risk of PE for GCS and pharmacological prophylaxis versus pharmacological prophylaxis alone was 0.71 (95% CI 0.0-30.0) (27 trial arms, 32 events, 11,472 participants). There were no between-group differences in VTE-related mortality (27 trial arms, 3 events, 12,982 participants).

CONCLUSIONS: Evidence from head-to-head meta-analysis and pooled trial arms demonstrates no additional benefit for GCS in preventing VTE and VTE-related mortality. GCS confer a risk of skin complications and an economic burden; current evidence does not support their use for surgical inpatients.

PMID:37753655 | DOI:10.1097/SLA.0000000000006096

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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

Effect of factor XI inhibition on tumor cell-induced coagulation activation

J Thromb Haemost. 2023 Sep 24:S1538-7836(23)00717-1. doi: 10.1016/j.jtha.2023.09.015. Online ahead of print.

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

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PubMed articles on: Cancer & VTE/PE

ABO Blood Group and the Risk of Thrombosis in Cancer Patients: A Mini-Review

Semin Thromb Hemost. 2023 Sep 26. doi: 10.1055/s-0043-1775568. Online ahead of print.

ABSTRACT

It is well established that direct oral anticoagulants (DOACs) are the cornerstone of anticoagulant strategy in atrial fibrillation (AF) and venous thromboembolism (VTE) and should be preferred over vitamin K antagonists (VKAs) since they are superior or non-inferior to VKAs in reducing thromboembolic risk and are associated with a lower risk of intracranial hemorrhage (IH). In addition, many factors, such as fewer pharmacokinetic interactions and less need for monitoring, contribute to the favor of this therapeutic strategy. Although DOACs represent a more suitable option, several issues should be considered in clinical practice, including drug-drug interactions (DDIs), switching to other antithrombotic therapies, preprocedural and postprocedural periods, and the use in patients with chronic renal and liver failure and in those with cancer. Furthermore, adherence to DOACs appears to remain suboptimal. This narrative review aims to provide a practical guide for DOAC prescription and address challenging scenarios.

PMID:37762897 | DOI:10.3390/jcm12185955

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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 | DOI:10.3390/cancers15184640

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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 | DOI:10.3390/cancers15184588

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PubMed articles on: Cancer & VTE/PE

Oral Anticoagulants Beyond Warfarin

Annu Rev Pharmacol Toxicol. 2023 Sep 27. doi: 10.1146/annurev-pharmtox-032823-122811. Online ahead of print.

ABSTRACT

Direct oral anticoagulants (DOACs) have largely replaced vitamin K antagonists, mostly warfarin, for the main indications for oral anticoagulation, prevention and treatment of venous thromboembolism, and prevention of embolic stroke in atrial fibrillation. While DOACs offer practical, fixed-dose anticoagulation in many patients, specific restrictions or contraindications may apply. DOACs are not sufficiently effective in high-thrombotic risk conditions such as antiphospholipid syndrome and mechanical heart valves. Patients with cancer-associated thrombosis may benefit from DOACs, but the bleeding risk, particularly in those with gastrointestinal or urogenital tumors, must be carefully weighed. In patients with frailty, excess body weight, and/or moderate-to-severe chronic kidney disease, DOACs must be cautiously administered and may require laboratory monitoring. Reversal agents have been developed and approved for life-threatening bleeding. In addition, the clinical testing of potentially safer anticoagulants such as factor XI(a) inhibitors is important to further optimize anticoagulant therapy in an increasingly elderly and frail population worldwide. Expected final online publication date for the Annual Review of Pharmacology and Toxicology, Volume 64 is January 2024. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

PMID:37758192 | DOI:10.1146/annurev-pharmtox-032823-122811

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PubMed articles on: Cancer & VTE/PE

Venous thromboembolism prophylaxis practices for patients with sickle cell disease prior to and during the COVID-19 pandemic

Blood Coagul Fibrinolysis. 2023 Sep 21. doi: 10.1097/MBC.0000000000001250. Online ahead of print.

ABSTRACT

Patients with sickle cell disease (SCD) are predisposed to a hypercoagulable state due to alterations in the coagulation system. Despite concern for the development of venous thromboembolism (VTE) in this population, there are no standardized guidelines for routine thromboprophylaxis. The objective of this study was to assess thromboprophylaxis practices of adult and pediatric treaters of SCD before and during the coronavirus disease of 2019 (COVID-19) pandemic. A cross-sectional electronic survey was distributed to pediatric and adult hematology oncology practitioners through seven SCD-specific interest groups between May 29, 2020, and July 13, 2020. Of 93 total responses, 14% (N = 13) reported they only treat patients more than 21 years old; 38.7% (N = 36) only treat patients 0-21 years old and 47.3% (N = 44) reported they treat both. Our study showed that before the COVID-19 pandemic, 96% of adult practitioners would recommend pharmacologic thromboprophylaxis, mechanical thromboprophylaxis or both for hospitalized adults with thromboprophylaxis, but only 76% of pediatric treaters would recommend any thromboprophylaxis in hospitalized children (P < 0.0001), with 24% of pediatric treaters choosing no thromboprophylaxis at all. During the COVID-19 pandemic, pharmacologic thromboprophylaxis specifically was recommended for adults by 94% of treaters and for pediatric patients by 76% of treaters. These findings suggest that despite the lack of evidence-based thromboprophylaxis guidelines in adults and children with thromboprophylaxis, subspecialty treaters routinely provide pharmacologic thromboprophylaxis in their adult patients and will modify their practice in pediatric patients who are considered at a high risk for VTE.

PMID:37756203 | DOI:10.1097/MBC.0000000000001250

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PubMed articles on: Cancer & VTE/PE

Correction to: Epidemiological Study Regarding the Incidence of Venous Thromboembolism in Patients After Cancer Remission

Cardiol Ther. 2023 Sep 27. doi: 10.1007/s40119-023-00330-9. Online ahead of print.

NO ABSTRACT

PMID:37755611 | DOI:10.1007/s40119-023-00330-9

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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

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PubMed articles on: Cancer & VTE/PE

An Updated Systematic Review and Meta-Analysis of the Impact of Graduated Compression Stockings in Addition to Pharmacological Thromboprophylaxis for Prevention of Venous Thromboembolism in Surgical Inpatients

Ann Surg. 2023 Sep 27. doi: 10.1097/SLA.0000000000006096. Online ahead of print.

ABSTRACT

BACKGROUND: Venous thromboembolism (VTE) is a leading cause of preventable mortality among hospitalized patients, but appropriate risk assessment and thromboprophylaxis remain underutilized or misapplied.

OBJECTIVES: We conducted an electronic survey of US health care providers to explore attitudes, practices, and barriers related to thromboprophylaxis in adult hospitalized patients and at discharge.

RESULTS: A total of 607 US respondents completed the survey: 63.1% reported working in an academic hospital, 70.7% identified as physicians, and hospital medicine was the most frequent specialty (52.1%). The majority of respondents agreed that VTE prophylaxis is important (98.8%; 95% CI: 97.6%-99.5%) and that current measures are safe (92.6%; 95% CI: 90.2%-94.5%) and effective (93.8%; 95% CI: 91.6%-95.6%), but only half (52.0%; 95% CI: 47.9%-56.0%) believed that hospitalized patients at their institution are on appropriate VTE prophylaxis almost all the time. One-third (35.4%) reported using a risk assessment model (RAM) to determine VTE prophylaxis need; 44.9% reported unfamiliarity with RAMs. The most common recommendation for improving rates of appropriate thromboprophylaxis was to leverage technology. A majority of respondents (84.5%) do not reassess a patient's need for VTE prophylaxis at discharge, and a minority educates patients about the risk (16.2%) or symptoms (18.9%) of VTE at discharge.

CONCLUSION: Despite guideline recommendations to use RAMs, the majority of providers in our survey do not use them. A majority of respondents believed that technology could help improve VTE prophylaxis rates. A majority of respondents do not reassess the risk of VTE at discharge or educate patients about this risk of VTE at discharge.

PMID:37767063 | PMC:PMC10520566 | DOI:10.1016/j.rpth.2023.102168

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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.

ABSTRACT

Optimizing the anticoagulation therapy is of pivotal importance in patients with a malignant tumor, as venous thromboembolism (VTE) has become the second-leading cause of death in this population. Cancer can highly increase the risk of thrombosis and bleeding. Consequently, the management of cancer-associated VTE is complex. In recent years, translational research has intensified, and several studies have highlighted the role of inflammatory cytokines in cancer growth and progression. Simultaneously, the pleiotropic effects of anticoagulants currently recommended for VTE have emerged. In this review, we describe the anti-inflammatory and anticancer effects of both direct oral anticoagulants (DOACs) and low-molecular-weight heparins (LWMHs).

PMID:37763292 | DOI:10.3390/life13091888

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PubMed articles on: Cancer & VTE/PE

The Risk of Thromboembolism in Patients with Muscle Invasive Bladder Cancer before and after Cystectomy Depending on Blood Group and Neoadjuvant Chemotherapy-A Multicentre Retrospective Cohort Study

J Pers Med. 2023 Sep 4;13(9):1355. doi: 10.3390/jpm13091355.

ABSTRACT

PURPOSE: Previous studies have indicated that patients with muscle-invasive bladder cancer with non-O blood types have an increased risk of experiencing thromboembolic events (TEEs). This is finding is in relation to neoadjuvant-chemotherapy (NAC)-naïve patients.

AIM: to establish the risk of TEEs and any association with blood types among NAC patients as well as NAC-naïve patients.

METHODS: Cystectomized patients at four centres treated from 2009 to 2018 (n = 244) were analysed. The quantities of patients corresponding to each blood group were as follows: A-108 (44%); O-99 (41%); B-30 (12%); and AB-7 (3%). NAC patients (n = 167) and NAC-naïve NAC-eligible patients (n = 77) were assessed. In total, 54 women (22%) and 190 men (78%), with a median age of 69 years, were included in the study. The occurrence of any type of TEE from six months pre-cystectomy to 12-24 months after was analysed using logistic regression adjusted for NAC and confounders.

RESULTS: Sixty-six TEEs were detected in 21% of the patients (n = 52). Pulmonary embolus (n = 33) and deep venous thrombosis (n = 11) were the most common forms. No significant differences between blood types were found in the analysis, although B blood type had a nearly significant increased crude risk compared with O blood type, for which there was an OR of 2.48 (95% CI 0.98-6.36). Adjustment for NAC and covariates weakened the OR, which plummeted to 1.98 (95% CI 0.71-5.51).

CONCLUSIONS: No significant associations were found between blood types and TEE occurrences in this cohort including both NAC and NAC-naïve NAC-eligible patients.

PMID:37763123 | DOI:10.3390/jpm13091355

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PubMed articles on: Cancer & VTE/PE

ReLiFiRa (Real Life Filgotinib in Rheumatoid Arthritis): Retrospective Study of Efficacy and Safety in Common Clinical Practice

J Pers Med. 2023 Aug 25;13(9):1303. doi: 10.3390/jpm13091303.

ABSTRACT

BACKGROUND: Filgotinib (FIL) is a selective JAK1 inhibitor with an affinity 30-fold higher than JAK2, approved to treat moderate to severe active rheumatoid arthritis (RA), in adults with inadequate response or intolerance to one or more disease-modifying antirheumatic drugs (DMARDs).

METHODS: We conducted a retrospective, multicentric study in order to evaluate efficacy and safety of FIL 200 mg daily therapy, after 3 and 6 months, in 120 patients affected by RA, managed in Tuscany and Umbria rheumatological centers. The following clinical records were analyzed: demographical data, smoking status, previous presence of comorbidities (Herpes zoster -HZ- infection, venous thromboembolism -VTE-, major adverse cardiovascular events -MACE-, cancer, diabetes, and hypertension), disease duration, presence of anti-citrullinated protein antibodies (ACPA), rheumatoid factor (RF), number of biological failures, and prior csDMARDs utilized. At baseline, and after 3 (T3) and 6 (T6) months of FIL therapy, we evaluated mean steroid dosage, csDMARDs intake, clinimetric indexes (DAS28, CDAI, HAQ, patient and doctor PGA, VAS), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and body mass index (BMI).

RESULTS: At baseline, the mean disease duration was 9.4 ± 7.5 years; the prevalence of previous HZ infection, VTE, MACE, and cancer was respectively 4.12%, 0%, 7.21%, and 0.83%, respectively. In total, 76.3% of patients failed one or more biologics (one biological failure, 20.6%; two biological failures, 27.8%; three biological failures, 16.5%; four biological failures, 10.3%; five biological failures, 1.1%). After 3 months of FIL therapy, all clinimetric index results significantly improved from baseline, as well as after 6 months. Also, ESR and CRP significatively decreased at T3 and T6. Two cases of HZ were recorded, while no new MACE, VTE, or cancer were recorded during the observation time.

CONCLUSION: Despite the limitations of the retrospective study and of the observational period of only 6 months, real-life data on the treatment of RA patients with FIL demonstrate that this Jak inhibitor therapy is safe in terms of CV, VTE events, and occurrence of cancer, and is also effective in a population identified as "difficult to treat" due to failure of previous b-DMARD therapy.

PMID:37763071 | DOI:10.3390/jpm13091303

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PubMed articles on: Cancer & VTE/PE

Management of Patients Treated with Direct Oral Anticoagulants in Clinical Practice and Challenging Scenarios

J Clin Med. 2023 Sep 13;12(18):5955. doi: 10.3390/jcm12185955.

ABSTRACT

OBJECTIVES: The effect of one-lung ventilation (OLV) strategy based on low tidal volume (TV), application of positive end-expiratory pressure (PEEP), and alveolar recruitment maneuvers (ARM) to reduce postoperative acute respiratory distress syndrome (ARDS) and pulmonary complications (PPCs) compared with higher TV without PEEP and ARM strategy in adult patients undergoing lobectomy or pneumonectomy has not been well established.

DESIGN: Multicenter, randomized, single-blind, controlled trial.

SETTING: Sixteen Italian hospitals.

PARTICIPANTS: A total of 880 patients undergoing elective major lung resection.

INTERVENTIONS: Patients were randomized to receive lower tidal volume (LTV group: 4 mL/kg predicted body weight, PEEP of 5 cmH2O, and ARMs) or higher tidal volume (HTL group: 6 mL/kg predicted body weight, no PEEP, and no ARMs). After OLV, until extubation, both groups were ventilated using a tidal volume of 8 mL/kg and a PEEP value of 5 cmH2O. The primary outcome was the incidence of in-hospital ARDS. Secondary outcomes were the in-hospital rate of PPCs, major cardiovascular events, unplanned intensive care unit (ICU) admission, in-hospital mortality, ICU length of stay, and in-hospital length of stay.

MEASUREMENTS AND MAIN RESULTS: ARDS occurred in 3 of 438 patients (0.7%, 95% CI 0.1-2.0) and in 1 of 442 patients (0.2%, 95% CI 0-1.4) in the LTV and HTV group, respectively (Risk ratio: 3.03 95% CI 0.32-29, p = 0.372). Pulmonary complications occurred in 125 of 438 patients (28.5%, 95% CI 24.5-32.9) and in 136 of 442 patients (30.8%, 95% CI 26.6-35.2) in the LTV and HTV group, respectively (risk ratio: 0.93, 95% CI 0.76-1.14, p = 0.507). The incidence of major complications, in-hospital mortality, and unplanned ICU admission, ICU and in-hospital length of stay were comparable in both groups.

CONCLUSIONS: In conclusion, among adult patients undergoing elective lung resection, an OLV with lower tidal volume, PEEP 5 cmH2O, and ARMs and a higher tidal volume strategy resulted in low ARDS incidence and comparable postoperative complications, in-hospital length of stay, and mortality.

PMID:37730455 | PMC:PMC10133024 | DOI:10.1053/j.jvca.2023.04.029

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PubMed articles on: Cardio-Oncology

Computational drug prediction in hepatoblastoma by integrating pan-cancer transcriptomics with pharmacological response

Hepatology. 2023 Sep 20. doi: 10.1097/HEP.0000000000000601. Online ahead of print.

ABSTRACT

Hepatoblastoma (HB) is the main paediatric liver cancer, but it is a very rare disease. Despite significant improvements in the treatment of children diagnosed with HB, limited treatment options exist for patients with advanced tumours. Besides, survivors generally have long-term adverse effects derived from treatment such as ototoxicity, cardiotoxicity, delayed growth, and secondary tumours. Accordingly, there is an urgent need to define new and efficient therapeutic strategies for patients with HB. Computational methods to predict drug sensitivity from a tumour's transcriptome have been successfully applied for some common adult malignancies, but specific efforts in paediatric cancers are lacking because of paucity of data. In this study, we computationally screened the efficacy of drugs in HB patients with the aggressive C2 subtype and poor clinical outcome starting from their transcriptome. Our method utilized publicly available collections of pan-cancer transcriptional profiles and drug responses across 36 tumour types and 495 compounds. The drugs predicted to be most effective were experimentally validated using patient-derived xenograft (PDX) models of HB grown in vitro and in vivo. We thus identified two CDK9 inhibitors, alvocidib and dinaciclib as potent HB growth inhibitors for the high-risk C2 molecular subtype. We also found that in a cohort of 46 patients with HB, high CDK9 tumour expression was significantly associated with poor prognosis. Our work proves the usefulness of computational methods trained on pan-cancer datasets to reposition drugs in rare paediatric cancers such as HB, and to help clinicians in choosing the best treatment options for their patients.

PMID:37729391 | DOI:10.1097/HEP.0000000000000601

29 September 2023

00:30

Cardiotoxicity News

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 | DOI:10.1001/jamanetworkopen.2023.35311

00:30

PubMed articles on: Cancer & VTE/PE

Survey on the Knowledge and Management of Cancer-Associated Thrombosis (CAT) in Haemato-Oncology Patients with Thrombocytopenia among Haematologists and Haematology Residents in Nigeria

West Afr J Med. 2023 Sep 28;40(9):956-961.

ABSTRACT

BACKGROUND: Arterial or venous thrombosis can complicate cancer, and 20% of cancer patients may develop venous thromboembolic disorders. Venous thromboembolism (VTE) is common in some haematologic malignancies and may coexist with thrombocytopenia in those haematologic malignancies. We carried out this survey to assess the knowledge and practice of haematologists and resident doctors in haematology in Nigeria regarding the management of thrombocytopenia and cancer-associated thrombosis.

METHODS: This was a survey that was shared electronically with participants who were consultant haematologists and resident doctors in haematology in Nigeria..

RESULTS: There were 106 respondents, 70 (66%) of which were consultant haematologists. About a third (30.2%) of the respondents saw 6-10 patients with blood malignancies monthly. Fifty-seven (53.8%) of the respondents carried out risk assessment in their patients for cancer-associated thrombosis (CAT); 63 (59.4%) of the respondents saw 1-2 cancer patients with thrombosis in 3 months. The most common mode of treatment was pharmacological - 94 (88%) respondents used low molecular weight heparin. The most common haematologic malignancies associated with thrombocytopenia were acute leukaemias (69; 67%). The most common decision taken by respondents was to stop anticoagulants and transfuse platelets because the most frequent concern was the risk of bleeding in this group of patients.

CONCLUSION: Many haematologists and haematology residents had a high level of awareness, knowledge and good practice regarding thrombocytopenia with CAT in haematooncology patients; however, there is a need for improved knowledge and unified protocols for treatment in line with newer management guidelines.

PMID:37767996

00:30

PubMed articles on: Cancer & VTE/PE

Venous thromboembolism prophylaxis for hospitalized adult patients: a survey of US health care providers on attitudes and practices

Res Pract Thromb Haemost. 2023 Aug 7;7(6):102168. doi: 10.1016/j.rpth.2023.102168. eCollection 2023 Aug.

ABSTRACT

BACKGROUND: BRAF and MEK inhibition is a successful strategy in managing BRAF-mutant melanoma, even if the treatment-related toxicity is substantial. We analyzed the role of drug-drug interactions (DDI) on the toxicity profile of anti-BRAF/anti-MEK therapy.

METHODS: In this multicenter, observational, and retrospective study, DDIs were assessed using Drug-PIN software (V 2/23). The association between the Drug-PIN continuous score or the Drug-PIN traffic light and the occurrence of treatment-related toxicities and oncological outcomes was evaluated.

RESULTS: In total, 177 patients with advanced BRAF-mutated melanoma undergoing BRAF/MEK targeted therapy were included. All grade toxicity was registered in 79% of patients. Cardiovascular toxicities occurred in 31 patients (17.5%). Further, 94 (55.9%) patients had comorbidities requiring specific pharmacological treatments. The median Drug-PIN score significantly increased when the target combination was added to the patient's home therapy (p-value < 0.0001). Cardiovascular toxicity was significantly associated with the Drug-PIN score (p-value = 0.048). The Drug-PIN traffic light (p = 0.00821) and the Drug-PIN score (p = 0.0291) were seen to be significant predictors of cardiotoxicity. Patients with low-grade vs. high-grade interactions showed a better prognosis regarding overall survival (OS) (p = 0.0045) and progression-free survival (PFS) (p = 0.012). The survival analysis of the subgroup of patients with cardiological toxicity demonstrated that patients with low-grade vs. high-grade DDIs had better outcomes in terms of OS (p = 0.0012) and a trend toward significance in PFS (p = 0.068).

CONCLUSIONS: DDIs emerged as a critical issue for the risk of treatment-related cardiovascular toxicity. Our findings support the utility of DDI assessment in melanoma patients treated with BRAF/MEK inhibitors.

PMID:37760556 | DOI:10.3390/cancers15184587

20:29

PubMed articles on: Cardio-Oncology

Multicenter, Prospective, Randomized Controlled Trial of High-Sensitivity Cardiac Troponin I-Guided Combination Angiotensin Receptor Blockade and Beta-Blocker Therapy to Prevent Anthracycline Cardiotoxicity: The Cardiac CARE Trial

Circulation. 2023 Sep 25. doi: 10.1161/CIRCULATIONAHA.123.064274. Online ahead of print.

ABSTRACT

BACKGROUND: Anthracycline-induced cardiotoxicity has a variable incidence, and the development of left ventricular dysfunction is preceded by elevations in cardiac troponin concentrations. Beta-adrenergic receptor blocker and renin-angiotensin system inhibitor therapies have been associated with modest cardioprotective effects in unselected patients receiving anthracycline chemotherapy.

METHODS: In a multicenter, prospective, randomized, open-label, blinded end-point trial, patients with breast cancer and non-Hodgkin lymphoma receiving anthracycline chemotherapy underwent serial high-sensitivity cardiac troponin testing and cardiac magnetic resonance imaging before and 6 months after anthracycline treatment. Patients at high risk of cardiotoxicity (cardiac troponin I concentrations in the upper tertile during chemotherapy) were randomized to standard care plus cardioprotection (combination carvedilol and candesartan therapy) or standard care alone. The primary outcome was adjusted change in left ventricular ejection fraction at 6 months. In low-risk nonrandomized patients with cardiac troponin I concentrations in the lower 2 tertiles, we hypothesized the absence of a 6-month change in left ventricular ejection fraction and tested for equivalence of ±2%.

RESULTS: Between October 2017 and June 2021, 175 patients (mean age, 53 years; 87% female; 71% with breast cancer) were recruited. Patients randomized to cardioprotection (n=29) or standard care (n=28) had left ventricular ejection fractions of 69.4±7.4% and 69.1±6.1% at baseline and 65.7±6.6% and 64.9±5.9% 6 months after completion of chemotherapy, respectively. After adjustment for age, pretreatment left ventricular ejection fraction, and planned anthracycline dose, the estimated mean difference in 6-month left ventricular ejection fraction between the cardioprotection and standard care groups was -0.37% (95% CI, -3.59% to 2.85%; P=0.82). In low-risk nonrandomized patients, baseline and 6-month left ventricular ejection fractions were 69.3±5.7% and 66.4±6.3%, respectively: estimated mean difference, 2.87% (95% CI, 1.63%-4.10%; P=0.92, not equivalent).

CONCLUSIONS: Combination candesartan and carvedilol therapy had no demonstrable cardioprotective effect in patients receiving anthracycline-based chemotherapy with high-risk on-treatment cardiac troponin I concentrations. Low-risk nonrandomized patients had similar declines in left ventricular ejection fraction, bringing into question the utility of routine cardiac troponin monitoring. Furthermore, the modest declines in left ventricular ejection fraction suggest that the value and clinical impact of early cardioprotection therapy need to be better defined in patients receiving high-dose anthracycline.

REGISTRATION: URL: https://doi.org/10.1186/ISRCTN24439460; Unique identifier, ISRCTN24439460. URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=2017-000896-99; Unique identifier: EudraCT 2017-000896-99.

PMID:37746692 | DOI:10.1161/CIRCULATIONAHA.123.064274

20:29

PubMed articles on: Cancer & VTE/PE

Early identification of lung cancer patients with venous thromboembolism: development and validation of a risk prediction model

Thromb J. 2023 Sep 14;21(1):95. doi: 10.1186/s12959-023-00544-w.

ABSTRACT

INTRODUCTION: Venous thromboembolism(VTE) is a leading cause of death in patients with lung cancer. Furthermore, hospitalization of patients with advanced lung cancer for VTE treatment represents a major economic burden on the national public health resources. Therefore, we performed this prospective study to identify clinical biomarkers for the early identification of VTE in lung cancer patients.

METHODS: This prospective study enrolled 158 patients with confirmed lung cancer, including 27 who were diagnosed with VTE within six months of the follow-up after lung cancer diagnosis. Multivariate logistic regression analysis was used to evaluate the diagnostic performancese of all the relevant clinical features and laboratory indicators in identifying lung cancer patients with a higher risk of VTE. A novel risk prediction model was constructed consisting of five clinical variables with the best diagnostic performances and was validated using the receiver operation characteristic(ROC) curves. The diagnostic performances of the new risk prediction model was also compared with the Khorana risk score (KRS) and the Padua risk score (PRS).

RESULTS: The VTE group of lung cancer patients (n = 27) showed significantly higher serum levels of fibrin degradation products (FDP), D-dimer, thrombomodulin (TM), thrombin-antithrombin-complex (TAT), α2-plasmin inhibitor-plasmin Complex (PIC), and tissue plasminogen activator-plasminogen activator inhibitor complex (t-PAIC) compared to those in the non-VTE group (n = 131). ROC curve analyses showed that the diagnostic efficacy of the new VTE risk prediction model with TM ≥ 9.75 TU/ml, TAT ≥ 2.25ng/ml, t-PAIC ≥ 7.35ng/ml, history of VTE, and ECOG PS score ≥ 2 was superior than the KRS and the PRS in the early identification of lung cancer patients with a higher risk of VTE.

CONCLUSIONS: The new risk prediction model showed significantly high diagnostic efficacy in the early identification of lung cancer patients with a high risk of VTE. The diagnostic efficacy of the new risk prediction model was higher than the KRS and the PRS in this cohort of lung cancer patients.

PMID:37710256 | PMC:PMC10500728 | DOI:10.1186/s12959-023-00544-w

20:29

PubMed articles on: Cardio-Oncology

Evaluation of Expression Level of miR-3135b-5p in Blood Samples of Breast Cancer Patients Experiencing Chemotherapy-Induced Cardiotoxicity

Indian J Clin Biochem. 2023 Oct;38(4):536-540. doi: 10.1007/s12291-022-01075-3. Epub 2022 Sep 6.

ABSTRACT

The efficacy of chemotherapeutics in the treatment of breast cancer is limited by cardiotoxicity, which could lead to irreversible heart failure. The evaluation of miRNA levels as a vital biomarker could predict cardiotoxicity induced by chemotherapy. According to our previous meta-analysis study on patients with heart failure, we found that miR-3135b had a significant increase in patients with heart failure. Therefore, the present study aimed to evaluate the expression level of miR-3135b in the blood sample of patients experiencing chemotherapy-induced cardiotoxicity. Blood samples were collected from breast cancer patients or breast cancer patients who had received chemotherapy and had not experienced any chemotherapy-induced cardiotoxicity (N = 37, control group) and breast cancer patients experiencing chemotherapy-induced cardiotoxicity after chemotherapy (N = 33). The expression level of miR-3135b was evaluated using real-time polymerase chain reaction (RT-PCR). The 2-ΔCt values of miR-3135b were compared between two groups. We observed a significant increase in the expression level of miR-3135b between patients experiencing chemotherapy-induced cardiotoxicity and the control group (P = 0.0001). Besides, the ejection fraction parameter was correlated with the expression level of miR-3135b (r = 0.5 and P = 0.0001). To sum up, miR-3135b might be useful as a promising circulating biomarker in predicting cardiotoxicity induced by chemotherapy. However, more studies are needed to validate miR-3135b as a biomarker for the diagnosis of chemotherapy-induced cardiotoxicity.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12291-022-01075-3.

PMID:37746544 | PMC:PMC10516830 | DOI:10.1007/s12291-022-01075-3