SummaryVenous thromboembolism (VTE) is the second leading cause of death in patients with cancer. These patients are at a high risk of VTE recurrence and bleeding during anticoagulant therapy. The ...International Initiative on Thrombosis and Cancer is an independent academic working group aimed at establishing a global consensus for the treatment and prophylaxis of VTE in patients with cancer. The International Initiative on Thrombosis and Cancer last updated its evidence-based clinical practice guidelines in 2016 with a free, web-based mobile phone application, which was subsequently endorsed by the International Society on Thrombosis and Haemostasis. The 2019 International Initiative on Thrombosis and Cancer clinical practice guidelines, which are based on a systematic review of the literature published up to December, 2018, are presented along with a Grading of Recommendations Assessment Development and Evaluation scale methods, with the support of the French National Cancer Institute. These guidelines were reviewed by an expanded international advisory committee and endorsed by the International Society on Thrombosis and Haemostasis. Results from head-to-head clinical trials that compared direct oral anticoagulant with low-molecular-weight heparin are also summarised, along with new evidence for the treatment and prophylaxis of VTE in patients with cancer.
Symptomatic venous thromboembolism (VTE) occurs 4-7 times more frequently in cancer patients as compared to non-cancer patients. A significant number of risk factors, which can be subcategorised as ...patient-, cancer- or treatment-related, have been shown to influence the risk of VTE during malignancy and further incorporated in risk-assessment models. Safe and efficient thromboprophylaxis regimens allow substantial decreased in VTE rates, since VTE is most often a largely preventable disease, but thromboprophylaxis remains underused in cancer compared to non-cancer patients. If thromboprophylaxis is warranted in cancer patients undergoing surgery or hospitalised for acute medical illness or with a lower mobility in the absence of contraindications to anticoagulants, its benefit remains controversial in outpatients and may be limited to locally advanced or metastatic pancreatic or lung cancer treated with chemotherapy. The International Initiative on Thrombosis and Cancer-CME free mobile app (ios and android), based on the International Clinical Practice Guidelines (CPG), facilitates their implementation and dissemination of knowledge worldwide so as to improve VTE treatment and prophylaxis in cancer patients.
For a long time, blood coagulation and innate immunity have been viewed as interrelated responses. Recently, the presence of leukocytes at the sites of vessel injury has been described. Here we ...analyzed interaction of neutrophils, monocytes, and platelets in thrombus formation after a laser-induced injury in vivo. Neutrophils immediately adhered to injured vessels, preceding platelets, by binding to the activated endothelium via leukocyte function antigen-1–ICAM-1 interactions. Monocytes rolled on a thrombus 3 to 5 minutes postinjury. The kinetics of thrombus formation and fibrin generation were drastically reduced in low tissue factor (TF) mice whereas the absence of factor XII had no effect. In vitro, TF was detected in neutrophils. In vivo, the inhibition of neutrophil binding to the vessel wall reduced the presence of TF and diminished the generation of fibrin and platelet accumulation. Injection of wild-type neutrophils into low TF mice partially restored the activation of the blood coagulation cascade and accumulation of platelets. Our results show that the interaction of neutrophils with endothelial cells is a critical step preceding platelet accumulation for initiating arterial thrombosis in injured vessels. Targeting neutrophils interacting with endothelial cells may constitute an efficient strategy to reduce thrombosis.
Updated clinical practice guidelines recommend the long-term use of low-molecular-weight heparins or direct oral anticoagulants as the preferred option for the treatment of cancer-associated ...thrombosis (CAT), using a personalized approach matching the right drug to the right patient. In most cases, the benefit of anticoagulant therapy outweighs the risk. However, the long-term use of anticoagulants is associated with a non-negligible risk of bleeding, which constitutes a rare but serious adverse effect. Bleeding complications have been reported to be overall 2 to 3 times more frequent in cancer patients with CAT receiving anticoagulation than in non-cancer patients, with a reported incidence of major bleeding ranging from 2.4 to 16.0% in randomized controlled trials (RCT). In the absence of validated risk assessment model to predict the risk of bleeding in these patients, a careful evaluation of each individual profile, with adequate selection of the most appropriate anticoagulant for each individual patient, is warranted for overcoming management challenges, taking in account the numerous factors which may potentiate the overall bleeding risk in these complex patients, such as advanced or metastatic disease, older age, anemia, thrombocytopenia, renal impairment, liver dysfunction, and concomitant anticancer therapies. The purpose of this review is to call for awareness on bleeding complications as a major safety issue of CAT treatment and to summarize data from recent RCT and real-world studies on the incidence and risk factors for bleeding in this unique and challenging population to further help clinicians in decision-making.
Venous thromboembolism (VTE) is a common complication in patients with cancer and is associated with poor prognosis. Low-molecular-weight heparins (LMWHs) are the standard of care for the treatment ...of cancer-associated thrombosis. Primary VTE prophylaxis with LMWH is recommended after cancer surgery and in hospitalized patients with reduced mobility. However, owing to wide variations in VTE and bleeding risk, based on disease stage, anti-cancer treatments, and individual patient characteristics, routine primary prophylaxis is not recommended in ambulatory cancer patients undergoing chemotherapy. Efforts are under way to validate risk assessment models that will help identify those patients in whom the benefits of primary prophylaxis will outweigh the risks. In recent months, long-awaited dedicated clinical trials assessing the direct oral anticoagulants (DOACs) in patients with cancer have reported promising results. In comparison with the LMWHs, the DOACs were reported to be non-inferior to prevent VTE recurrence. However, there was an increased risk of bleeding, particularly in gastrointestinal cancers. Safe and optimal treatment with the DOACs in the patient with cancer will require vigilant patient selection based on patient characteristics, co-morbidities, and the potential for drug-drug interactions.
Objectives This study aimed to investigate the impact of ticagrelor on adenosine plasma concentration (APC) in acute coronary syndrome (ACS) patients. Background Ticagrelor is a direct-acting P2Y12 ...-adenosine diphosphate receptor blocker. The clinical benefit of ticagrelor compared with clopidogrel in ACS patients suggests that the drug has non–platelet-directed properties. Animal and in vitro models suggested that the “pleiotropic” properties of ticagrelor may be related to an interaction with adenosine metabolism. Methods We prospectively randomized 60 ACS patients to receive ticagrelor or clopidogrel. The APC was measured by liquid chromatography. To assess the mechanism of APC variation, we measured adenosine deaminase concentration, adenosine uptake by red blood cells, and cyclic adenosine monophosphate production by cells overexpressing adenosine receptors. The P2Y12 -adenosine diphosphate receptor blockade was assessed by the vasodilator-stimulated phosphoprotein index. Results Patients receiving ticagrelor had significantly higher APC than patients receiving clopidogrel (1.5 μM interquartile range: 0.98 to 1.7 μM vs. 0.68 μM interquartile range: 0.49 to 0.78 μM; p < 0.01). The APC was not correlated with vasodilator-stimulated phosphoprotein (p = 0.16). Serum-containing ticagrelor inhibited adenosine uptake by red blood cells compared with clopidogrel or controls (p < 0.01 for both comparisons). Adenosine deaminase activity was similar in serum of patients receiving clopidogrel or ticagrelor (p = 0.1). Ticagrelor and clopidogrel had no direct impact on adenosine receptors (p = not significant). Conclusions Ticagrelor increases APC in ACS patients compared with clopidogrel by inhibiting adenosine uptake by red blood cells.
International clinical practice guidelines have progressively endorsed direct oral anticoagulants (DOACs) as an alternative to low-molecular-weight heparins (LMWHs) monotherapy for the initial and ...long-term treatment of cancer-associated thrombosis (CAT). Several new randomized controlled trials (RCTs) have recently reported additional results on the safety and efficacy of DOACs in this setting. We performed an updated meta-analysis of all publicly available data from RCTs comparing DOACs with LMWHs for the treatment of CAT. Six RCTs enrolling 3690 patients with CAT were included. Compared with LMWHs, DOACs significantly decreased the risk of CAT recurrence (RR, 0.67; 95%CI, 0.52-0.85), with a non-significant increase in the risk of major bleeding (RR, 1.17; 95%CI, 0.82-1.67), a significant increase in the risk of clinically relevant nonmajor bleeding (RR 1.66; 95%CI, 1.31-2.09) and no difference in all-cause mortality rates. These results increase the level of certainty of available evidence supporting the use of DOACs as an effective and safe option for the treatment of CAT in selected cancer patients.
Venous thromboembolism (VTE) is a common cause of morbidity and mortality in cancer patients and leads to a significant increase in health care costs. Cancer patients often suffer from multiple ...co-morbidities and have both a greater risk of VTE recurrence and bleeding compared to non-cancer patients. Anticoagulation is therefore challenging. For many years, long-term therapy with Low-Molecular-Weight Heparin (LMWH) was the standard of care for the management of cancer-associated VTE. Direct oral anticoagulants (DOAC), which offer the convenience of an oral administration and have a rapid onset of action, have recently been proposed as a new option in this setting. Head-to-head comparisons between DOAC and LMWHs for the treatment of established VTE are now available, and data on the efficacy and safety of these drugs for primary prophylaxis of VTE in ambulatory cancer patients receiving systemic anticancer therapy are emerging. This narrative review aims to summarize the main recent advances in the prevention and treatment of cancer-associated VTE, including recent data on the use of individualized factors to stratify the risk of VTE in each individual patient, quality-of-life in patients treated with LMWH, and the place that DOACs will likely take in the cancer-associated VTE management landscape.
Pancreatic cancer (PC) is a devastating malignancy with fewer than 10% of patients being alive at 5 years after diagnosis. Venous thromboembolism (VTE) occurs in approximatively 20% of patients with ...PC, resulting in increased morbidity, mortality and significant health care costs. The management of VTE is particularly challenging in these frail patients. Adequate selection of the most appropriate anticoagulant for each individual patient according to the current international guidelines is warranted for overcoming treatment challenges. The International Initiative on Thrombosis and Cancer multi-language web-based mobile application (downloadable for free at
www.itaccme.com
) has been developed to help clinicians in decision making in the most complex situations. In this narrative review, we will discuss the contemporary epidemiology and burden of VTE in PC patients, the performances and limitations of current risk assessment models to predict the risk of VTE, as well as evidence from recent clinical trials for the primary prophylaxis and treatment of cancer-associated VTE that support up-dated clinical practice guidelines.
Women, thrombosis, and cancer Farge, Dominique; Le Maignan, Christine; Doucet, Ludovic ...
Thrombosis research,
09/2019, Letnik:
181
Journal Article
Recenzirano
ABSTRACTVenous thromboembolism (VTE) is a major common complication in cancer patients. Risk-adapted thromboprophylaxis and antithrombotic therapy for patients diagnosed with VTE can reduce the ...recurrence of VTE events. Thrombotic risk varies according to cancer type, stage, and comorbidities. The current review analyzes most recent data and provides clinical guidance for the management of women with cancer-associated thrombosis.
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