Risk Of Bleeding In Cancer Patients Research Articles

Assessment of bleeding risk in cancer patients treated with anticoagulants for venous thromboembolic events.

Anticoagulant is the cornerstone of the management of VTE at the cost of a non-negligible risk of bleeding. Reliable and validated clinical tools to predict thromboembolic and hemorrhagic events are crucial for individualized decision-making for the type and duration of anticoagulant treatment. We evaluate the available risk models in real life cancer patients with VTE. The objectives of the study were to describe the bleeding of cancer patients with VTE and to evaluate the performance of the different bleeding models to predict the risk of bleeding during a 6-month follow-up. VTE-diagnosed patient's demographic and clinical characteristics, treatment regimens and outcomes for up to 6 months were collected. The primary endpoint was the occurrence of a major bleeding (MB) or a clinically relevant non major bleeding (CRNMB) event, categorized according to the ISTH criteria. During the 6-months follow-up period, 26 out of 110 included patients (26.7%) experienced a bleeding event, with 3 recurrences of bleeding. Out of the 29 bleeding events, 19 events were CRNMB and 10 MB. One patient died because of a MB. Bleeding occurred in 27 % of the patients treated with DOACs and 22% of the patients treated with LMWH. Most of the bleedings were gastrointestinal (9 events, 31%); 26.9% of the bleedings occurred in patient with colorectal cancer and 19.6% in patients with lung cancer. In our cohort, none of the 10 RAMs used in our study were able to distinguish cancer patients with a low risk of bleeding, from all bleeding or non-bleeding patients. The Nieto et al. RAM had the best overall performance (C-statistic = 0.730, 95% CI (0.619-0.840)). However, it classified 1 out of 5 patients with major bleeding in the low risk of bleeding group. The rest of the RAMs showed a suboptimal result, with a range of C-statistic between 0.489, 95%CI (0.360-0.617)) and 0.532, 95%CI (0.406-0.658)). The management of CAT patients is challenging due to a higher risk of both recurrent VTE and bleeding events, as compared with non-cancer patients with VTE. None of the existing RAMs was able to consistently identify patients with risk of anticoagulant associated bleeding events.

Evaluation of bleeding risk between apixaban and rivaroxaban in patients with gastrointestinal cancer.

e16323 Background: Patients with cancer are at a higher risk for developing venous thromboembolisms (VTEs), leading to further complications. The National Comprehensive Cancer Network (NCCN) guidelines currently recommend using low-molecular-weight heparin (LMWH) or direct oral anticoagulants (DOACs) for the treatment of VTEs in oncology patients. Other trials compare DOACs with LMWH to determine the risk of bleeding. The Select-D trial found that rivaroxaban had a higher risk of bleeding in patients with gastrointestinal (GI) cancer as compared to LMWH. However, the Caravaggio trial found that apixaban had no increase of bleeding for patients with GI cancer. Due to the inherent risk of major bleeding shown in the subgroup analysis of the trials above, the guidelines recommend LMWH as the preferred agent for patients with GI cancers. At Winship Cancer Institute, DOACs are used for the treatment of cancer-associated VTE for patients with GI malignancies. The purpose of this study was to assess real-world safety outcomes of patients with GI cancer who were treated with apixaban or rivaroxaban for VTE. Methods: This study is a single-center, retrospective chart review of patients 18 years or older with GI cancer receiving treatment for VTE with either apixaban or rivaroxaban. The study looks to review bleeding outcomes in patients who started their VTE treatment from January 1, 2017 – December 31, 2021. The primary outcome of this study was to evaluate the rates of major bleeding between apixaban and rivaroxaban. Major bleeding was defined as a decrease in hemoglobin of ≥ 2g/dL over 24 hours, transfusion of ≥2 units of red blood cells, bleeding that requires surgical intervention, or bleeding at critical sites. Secondary outcomes included clinically relevant non-major bleeding (CRNMB) defined by bleeding compromising hemodynamics, hematemesis, hemoptysis, rectal bleeding, or hematuria, VTE recurrence, and death from bleeding. Data collected to measure these outcomes included patient characteristics such as renal function, weight, primary cancer site, medication dosing, and duration and indication of treatment. Results: A total of 300 patients qualified for inclusion of this study. Of these, 89 were in the apixaban group and 211 in the rivaroxaban group. Major bleeding occurred in 3 patients in the apixaban group (3.4%) and 18 in the rivaroxaban group (8.5%). CRNMB occurred in 2 patients in the apixaban group (2.2%) and 16 patients in the rivaroxaban group (7.6%). VTE recurrence occurred in 4 patients in the apixaban group (4.5%) and 9 patients in the rivaroxaban group (4.3%). Conclusions: This is the only study to date to evaluate DOACs head to head and their bleeding risk in cancer patients. Apixaban was associated with lower rates of major bleeds and CRNMB, but relatively similar rates of VTE recurrence. The results of this study warrant consideration of using DOACs for patients with GI cancers in the upfront setting.

Left Atrial Appendage Occlusion in Patients With Atrial Fibrillation andCancer.

The prevention of stroke in patients with atrial fibrillation (AF) and cancer is challenging because patients are at increased bleeding and thrombotic risk. The authors sought to assess left atrial appendage occlusion (LAAO) as a safe and effective strategy for reducing stroke at no increased bleeding risk in cancer patients with AF. We reviewed patients with nonvalvular AF who underwent LAAO at Mayo Clinic sites from 2017 to 2020 and identified those who had undergone prior or current treatment for cancer. We compared the incidence of stroke, bleeding, device complications, and death with a control group who underwent LAAO without malignancy. Fifty-five patients were included; 44 (80.0%) were male, and the mean age was 79.0 ± 6.1 years. The median CHA2Ds2-VASc score was 5 (Q1-Q3: 4-6), with 47 (85.5%) having a prior bleeding event. Over the first year, ischemic stroke occurred in 1 (1.4%) patient, bleeding complications in 5 (10.7%) patients, and death in 3 (6.5%) patients. Compared with controls who underwent LAAO without cancer, there was no significant difference in ischemic stroke (HR: 0.44; 95% CI: 0.10-1.97; P = 0.28), bleeding complication (HR: 0.71; 95% CI: 0.28-1.86; P = 0.19), or death (HR: 1.39; 95% CI: 0.73-2.64; P = 0.32). Within our cohort, LAAO in cancer patients was achieved with good procedural success and offered a reduction in stroke at no increased bleeding risk similar to noncancer patients.

Managing ischemic and bleeding risk in cancer patients presenting with acute coronary syndromes: A challenge accepted?

Managing ischemic and bleeding risk in cancer patients presenting with acute coronary syndromes: A challenge accepted?

Abstract 11688: Left Atrial Appendage Occlusion in Patients With Atrial Fibrillation and Cancer

Introduction: Prevention of stroke in patients with atrial fibrillation and cancer is challenging as patients are at increased bleeding and thrombotic risk. Left atrial appendage occlusion (LAAO) has evolved as a promising strategy for stroke prevention with protentional to reduce bleeding risk, though no data exists on its efficacy in patients with cancer. Hypothesis: LAAO is a safe and effective strategy for reducing stroke and bleeding risk in cancer patients with atrial fibrillation. Methods: We retrospectively reviewed all patients with nonvalvular atrial fibrillation who underwent LAAO at all Mayo Clinic sites from 2017-2020 and identified those who had undergone prior or current treatment for cancer. Baseline demographics, malignancy history, atrial fibrillation parameters, procedural success/complications, stroke and bleeding incidence and major adverse cardiac events were ascertained. Results: 55 patients were included in the study; 44 (80.0%) were male and mean age was 79.0 ± 6.1 years. Most common primary malignancies included prostate cancer (29.1%), oropharyngeal cancer (12.7%), and melanoma (10.9%) with 15 (27.3%) having metastatic disease and 14 (25.5%) patients having active malignancy at device implant. Mean CHA2DS2-Vasc score was 4.9 ± 1.3, with 47 (85.5%) patients having a prior bleeding event. Acute procedural success was achieved in all patients with 30-day complications including 4 (7.3%) with vascular access site bleeding, 1 (1.8%) with pericarditis and 1 (1.8%) with a seizure. At a follow up of 1.8 ± 1.1 years, ischemic stroke occurred in 2 (3.6%) patients with bleeding complications in 5 (9.1%) patients. Device related complications occurred in 6 (10.9%) patients with 4 (7.3%) with device thrombosis and 2 (3.6%) with a peri-device leak. Death occurred in 14 (25.5%) patients most commonly due to malignancy progression (9.1%) and infection (7.3%). Conclusions: In our study cohort, LAAO in patients with cancer was achieved with excellent procedural success and offered reasonable reduction in stroke and bleeding risk. Mortality was high likely due to the age of the patients studied, underlying malignancy and comorbidities. Further studies are needed to investigate the prevalence of device thrombosis in cancer patients.

Primary Thromboprophylaxis in Patients with Malignancies: Daily Practice Recommendations by the Hemostasis Working Party of the German Society of Hematology and Medical Oncology (DGHO), the Society of Thrombosis and Hemostasis Research (GTH), and the Austrian Society of Hematology and Oncology (ÖGHO).

Simple SummaryThromboembolic events occur in up to 20% of cancer patients during their course of disease. In addition, thromboembolism contributes relevantly to morbidity and mortality in this cohort. As a consequence, primary prophylaxis to prevent thromboembolic events is crucial. Due to enhanced bleeding risk in cancer patients, anticoagulation can be challenging in daily practice. Herein, we performed a systematic review regarding primary prophylaxis for thromboembolic events in cancer patients in order to aid clinicians in daily decision making. Besides general recommendations, specific subgroups were addressed, and recommendations are given at the end of each chapter. All topics were extensively reviewed and discussed among an expert panel including oncologists, hematologists, and hemostasis specialists, as members of the hemostasis working party of the German and Austrian Society of Hematology and Oncology as well as the German Society of Thrombosis and Hemostasis Research.Patients with cancer, both hematologic and solid malignancies, are at increased risk for thrombosis and thromboembolism. In addition to general risk factors such as immobility and major surgery, shared by non-cancer patients, cancer patients are exposed to specific thrombotic risk factors. These include, among other factors, cancer-induced hypercoagulation, and chemotherapy-mediated endothelial dysfunction as well as tumor-cell-derived microparticles. After an episode of thrombosis in a cancer patient, secondary thromboprophylaxis to prevent recurrent thromboembolism has long been established and is typically continued as long as the cancer is active or actively treated. On the other hand, primary prophylaxis, even though firmly established in hospitalized cancer patients, has only recently been studied in ambulatory patients. This recent change is mostly due to the emergence of direct oral anticoagulants (DOACs). DOACs have a shorter half-life than vitamin K antagonists (VKA), and they overcome the need for parenteral application, the latter of which is associated with low-molecular-weight heparins (LMWH) and can be difficult for the patient to endure in the long term. Here, first, we discuss the clinical trials of primary thromboprophylaxis in the population of cancer patients in general, including the use of VKA, LMWH, and DOACs, and the potential drug interactions with pre-existing medications that need to be taken into account. Second, we focus on special situations in cancer patients where primary prophylactic anticoagulation should be considered, including myeloma, major surgery, indwelling catheters, or immobilization, concomitant diseases such as renal insufficiency, liver disease, or thrombophilia, as well as situations with a high bleeding risk, particularly thrombocytopenia, and specific drugs that may require primary thromboprophylaxis. We provide a novel algorithm intended to aid specialists but also family practitioners and nurses who care for cancer patients in the decision process of primary thromboprophylaxis in the individual patient.

Tinzaparin Sodium Pharmacokinetics in Patients with Chronic Kidney Disease: Practical Implications.

Low-molecular-weight heparins (LMWHs) are the mainstay of the prophylaxis and treatment of venous thromboembolism (VTE). Due to their renal elimination, the risk of accumulation with the related bleeding risk may represent a limitation for the use of LMWHs in patients with chronic kidney disease (CKD) as the risk of major bleeding is increased in patients with creatinine clearance (CrCl) < 30 mL/min, especially in patients with cancer. LMWH structure and molecular weight (MW) are heterogeneous among available agents. The elimination of tinzaparin, which has the highest mean MW among LMWHs, is less dependent on renal function as it is also metabolized through the reticuloendothelial system. A subcutaneous therapeutic dose of tinzaparin (175 IU/kg) once daily has been shown to cause no accumulation of anti-factor Xa activity in patients with CrCl ≥ 20 mL/min. Clinical experience from randomized controlled studies has shown no significant impact of CKD on bleeding risk in cancer patients receiving treatment doses of tinzaparin. This suggests that in these patients the use of treatment doses of tinzaparin does not require anticoagulation monitoring or dose adjustment.

Bleeding risk in cancer patients treated with sorafenib: A meta-analysis of randomized controlled trials.

Sorafenib, an oral vascular endothelial growth factor receptor tyrosine-kinase inhibitor, has become a cornerstone in the treatment of various malignancies. However, concerns have arisen regarding the risk of hemorrhage with sorafenib use. Nevertheless, the contribution of sorafenib to hemorrhage and the underlying risk factors remains unclear. We performed a meta-analysis to determine the incidence and risk of hemorrhage associated with sorafenib treatment. Multiple databases were searched to identify relevant studies. The analysis included randomized controlled trials (RCTs) that directly compared cancer patients treated with or without sorafenib. Statistical analyses were conducted to determine the overall incidence, relative risks (RRs), and 95% confidence intervals (CIs) using fixed- or random-effect models. Ten RCTs involving 4720 patients were included in the analysis. Overall, the incidence rates of all- and high-grade hemorrhage in patients receiving sorafenib were 9.89% (95% CI: 8.73-11.18%) and 2.86% (95% CI: 2.25-3.63%), respectively. Sorafenib treatment increased the risk of all-grade hemorrhage in patients compared to control treatment (RR: 1.99; 95% CI: 1.59-2.49; P < 0.00001), but did not increase the incidence of high-grade hemorrhage (RR: 1.42; 95% CI: 0.95-2.12; P = 0.09). Subgroup analysis showed no significant increase in the risk of hemorrhage between patients with various malignancies or concurrent treatment. No evidence of publication bias was observed. In patients with malignancy, sorafenib treatment combined with standard treatment significantly increases the risk of low-grade hemorrhagic events.

P4623Increased bleeding risk in cancer patients with atrial fibrillation. Can we identify risk predictors?

P4623Increased bleeding risk in cancer patients with atrial fibrillation. Can we identify risk predictors?

Protein kinase A activation by the anti-cancer drugs ABT-737 and thymoquinone is caspase-3-dependent and correlates with platelet inhibition and apoptosis

Chemotherapy-induced thrombocytopenia is a common bleeding risk in cancer patients and limits chemotherapy dose and frequency. Recent data from mouse and human platelets revealed that activation of protein kinase A/G (PKA/PKG) not only inhibited thrombin/convulxin-induced platelet activation but also prevented the platelet pro-coagulant state. Here we investigated whether or not PKA/PKG activation could attenuate caspase-dependent apoptosis induced by the anti-cancer drugs ABT-737 (the precursor of navitoclax) and thymoquinone (TQ), thereby potentially limiting chemotherapy-induced thrombocytopenia. This is particularly relevant as activation of cyclic nucleotide signalling in combination chemotherapy is an emerging strategy in cancer treatment. However, PKA/PKG-activation, as monitored by phosphorylation of Vasodilator-stimulated phosphoprotein (VASP), did not block caspase-3-dependent platelet apoptosis induced by the compounds. In contrast, both substances induced PKA activation themselves and PKA activation correlated with platelet inhibition and apoptosis. Surprisingly, ABT-737- and TQ-induced VASP-phosphorylation was independent of cAMP levels and neither cyclases nor phosphatases were affected by the drugs. In contrast, however, ABT-737- and TQ-induced PKA activation was blocked by caspase-3 inhibitors. In conclusion, we show that ABT-737 and TQ activate PKA in a caspase-3-dependent manner, which correlates with platelet inhibition and apoptosis and therefore potentially contributes to the bleeding risk in chemotherapy patients.