Special Issue "The Role of Thrombosis and Haemostasis in Cancer"

A special issue of Cancers (ISSN 2072-6694).

Deadline for manuscript submissions: closed (30 November 2018)

Special Issue Editors

Guest Editor
Prof. Dr. Marco Falasca

School of Pharmacy & Biomedical Sciences, Faculty of Health Science, Curtin University, Perth, Australia
Website | E-Mail
Interests: signal transduction; cancer invasion and metastasis; phosphoinositide signalling; PI3-kinase/PDK1 signalling pathway; ABC transporters; G protein-coupled receptors; exosomes
Guest Editor
Dr. Pat Metharom

Platelet Research Laboratory, Curtin Health and Innovation Research Institute, Faculty of Health Sciences, Curtin University, Perth, WA, Australia
Website | E-Mail
Phone: 0892669271
Interests: platelet biology; signal transduction; cancer-associated thrombosis

Special Issue Information

Dear Colleagues,

Cancer-associated thrombosis is a lethal complication in cancer sufferers. The association between malignancy and thrombosis was first described over a century and half ago, by Jean-Baptiste Bouillard in 1823 and later in 1865 by Armand Trousseau. It is now well accepted that cancer patients are at an estimated four to seven-fold increased risk of developing venous thromboembolism (VTE) compared to non-cancer patients. The mechanisms by which cancer elicit thromboembolic events are not entirely understood. A significant role is attributed to the capability of cancer cells to activate the coagulation system, thus inducing a hypercoagulable or prothrombotic state in cancer patients. Cancer cells can activate the coagulation cascade through the expression of tissue factor, the release of proinflammatory cytokines, and interactions with endothelial and circulating blood cells. Platelets, a key regulator cell population of haemostasis and thrombosis, are known to be an important contributor of VTE, not only to through their involvement in thrombus formation but also in promoting cancer survival and spread. Recently, neutrophils are implicated as an important mediator of cancer-associated thrombosis. Neutrophil extracellular traps (NETs), released from activated neutrophils, have been reported in tumour samples and their presence in vivo is associated with metastasis. 

This Special Issue will cover the current research of thrombosis and haemostasis in cancer development. Both basic mechanisms underlying the processes, clinical observations and therapeutic implications of targeting key regulators of thrombosis and haemostasis will be discussed

Prof. Dr. Marco Falasca
Dr. Pat Metharom
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • cancer biology
  • cancer-associated thrombosis
  • platelets
  • metastasis
  • neutrophils

Published Papers (15 papers)

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Editorial

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Open AccessEditorial The History of Armand Trousseau and Cancer-Associated Thrombosis
Cancers 2019, 11(2), 158; https://doi.org/10.3390/cancers11020158
Received: 29 January 2019 / Accepted: 30 January 2019 / Published: 31 January 2019
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Abstract
“Je suis perdu; une phlegmatia qui vient de se déclarer cette nuit, ne me laisse aucun doute sur nature de mon mal [...] Full article
(This article belongs to the Special Issue The Role of Thrombosis and Haemostasis in Cancer)
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Research

Jump to: Editorial, Review

Open AccessArticle Inhibition of NK Reactivity Against Solid Tumors by Platelet-Derived RANKL
Cancers 2019, 11(3), 277; https://doi.org/10.3390/cancers11030277
Received: 29 January 2019 / Revised: 20 February 2019 / Accepted: 21 February 2019 / Published: 26 February 2019
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Abstract
NK cells play an important role in tumor immunosurveillance. Their reactivity is governed by various activating and inhibitory surface receptors, which include several members of the TNF/TNF receptor family. For more than 50 years, it has been recognized that tumor immunosurveillance and in [...] Read more.
NK cells play an important role in tumor immunosurveillance. Their reactivity is governed by various activating and inhibitory surface receptors, which include several members of the TNF/TNF receptor family. For more than 50 years, it has been recognized that tumor immunosurveillance and in particular NK cell antitumor reactivity is largely influenced by platelets, but the underlying mechanisms remain to be fully elucidated. Here we report that upon activation, which reportedly occurs following interaction with cancer cells, platelets upregulate the TNF family member RANKL. Comparative analysis of the expression of RANK among different NK cell subsets and RANKL on platelets in cancer patients and healthy volunteers revealed a distinct malignant phenotype, and platelet-derived RANKL was found to inhibit the activity of normal NK cells against cancer cells. Notably, NK cell antitumor reactivity could be partially restored by application of denosumab, a RANKL-neutralizing antibody approved for treatment of benign and malignant osteolysis. Together, our data not only unravel a novel mechanism of tumor immune evasion mediated by platelets, but they also provide a functional explanation for the clinical observation that denosumab, beyond protecting from bone loss, may prolong disease-free survival in patients with solid tumors. Full article
(This article belongs to the Special Issue The Role of Thrombosis and Haemostasis in Cancer)
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Open AccessArticle Dynamic Thromboembolic Risk Modelling to Target Appropriate Preventative Strategies for Patients with Non-Small Cell Lung Cancer
Received: 18 December 2018 / Accepted: 29 December 2018 / Published: 8 January 2019
Cited by 1 | PDF Full-text (771 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Prevention of cancer-associated thromboembolism (TE) remains a significant clinical challenge and priority world-wide safety initiative. In this prospective non-small cell lung cancer (NSCLC) cohort, longitudinal TE risk profiling (clinical and biomarker) was undertaken to develop risk stratification models for targeted TE prevention. These [...] Read more.
Prevention of cancer-associated thromboembolism (TE) remains a significant clinical challenge and priority world-wide safety initiative. In this prospective non-small cell lung cancer (NSCLC) cohort, longitudinal TE risk profiling (clinical and biomarker) was undertaken to develop risk stratification models for targeted TE prevention. These were compared with published models from Khorana, CATS, PROTECHT, CONKO, and CATS/MICA. The NSCLC cohort of 129 patients, median follow-up 22.0 months (range 5.6—31.3), demonstrated a hypercoagulable profile in >75% patients and TE incidence of 19%. High TE risk patients were those receiving chemotherapy with baseline fibrinogen ≥ 4 g/L and d-dimer ≥ 0.5 mg/L; or baseline d-dimer ≥ 1.5 mg/L; or month 1 d-dimer ≥ 1.5 mg/L. The model predicted TE with 100% sensitivity and 34% specificity (c-index 0.67), with TE incidence 27% vs. 0% for high vs. low-risk. A comparison using the Khorana, PROTECHT, and CONKO methods were not discriminatory; TE incidence 17–25% vs. 14–19% for high vs. low-risk (c-index 0.51–0.59). Continuous d-dimer (CATS/MICA model) was also not predictive of TE. Independent of tumour stage, high TE risk was associated with cancer progression (HR 1.9, p = 0.01) and mortality (HR 2.2, p = 0.02). The model was tested for scalability in a prospective gastrointestinal cancer cohort with equipotency demonstrated; 80% sensitivity and 39% specificity. This proposed TE risk prediction model is simple, practical, potent and can be used in the clinic for real-time, decision-making for targeted thromboprophylaxis. Validation in a multicentre randomised interventional study is underway (ACTRN12618000811202). Full article
(This article belongs to the Special Issue The Role of Thrombosis and Haemostasis in Cancer)
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Review

Jump to: Editorial, Research

Open AccessFeature PaperReview Thrombin Generation and Cancer: Contributors and Consequences
Cancers 2019, 11(1), 100; https://doi.org/10.3390/cancers11010100
Received: 1 December 2018 / Revised: 4 January 2019 / Accepted: 8 January 2019 / Published: 16 January 2019
Cited by 1 | PDF Full-text (608 KB) | HTML Full-text | XML Full-text
Abstract
The high occurrence of cancer-associated thrombosis is associated with elevated thrombin generation. Tumour cells increase the potential for thrombin generation both directly, through the expression and release of procoagulant factors, and indirectly, through signals that activate other cell types (including platelets, leukocytes and [...] Read more.
The high occurrence of cancer-associated thrombosis is associated with elevated thrombin generation. Tumour cells increase the potential for thrombin generation both directly, through the expression and release of procoagulant factors, and indirectly, through signals that activate other cell types (including platelets, leukocytes and erythrocytes). Furthermore, cancer treatments can worsen these effects. Coagulation factors, including tissue factor, and inhibitors of coagulation are altered and extracellular vesicles (EVs), which can promote and support thrombin generation, are released by tumour and other cells. Some phosphatidylserine-expressing platelet subsets and platelet-derived EVs provide the surface required for the assembly of coagulation factors essential for thrombin generation in vivo. This review will explore the causes of increased thrombin production in cancer, and the availability and utility of tests and biomarkers. Increased thrombin production not only increases blood coagulation, but also promotes tumour growth and metastasis and as a consequence, thrombin and its contributors present opportunities for treatment of cancer-associated thrombosis and cancer itself. Full article
(This article belongs to the Special Issue The Role of Thrombosis and Haemostasis in Cancer)
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Open AccessReview Predicting VTE in Cancer Patients: Candidate Biomarkers and Risk Assessment Models
Received: 14 November 2018 / Revised: 7 December 2018 / Accepted: 8 January 2019 / Published: 15 January 2019
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Abstract
Risk prediction of chemotherapy-associated venous thromboembolism (VTE) is a compelling challenge in contemporary oncology, as VTE may result in treatment delays, impaired quality of life, and increased mortality. Current guidelines do not recommend thromboprophylaxis for primary prevention, but assessment of the patient’s individual [...] Read more.
Risk prediction of chemotherapy-associated venous thromboembolism (VTE) is a compelling challenge in contemporary oncology, as VTE may result in treatment delays, impaired quality of life, and increased mortality. Current guidelines do not recommend thromboprophylaxis for primary prevention, but assessment of the patient’s individual risk of VTE prior to chemotherapy is generally advocated. In recent years, efforts have been devoted to building accurate predictive tools for VTE risk assessment in cancer patients. This review focuses on candidate biomarkers and prediction models currently under investigation, considering their advantages and disadvantages, and discussing their diagnostic performance and potential pitfalls. Full article
(This article belongs to the Special Issue The Role of Thrombosis and Haemostasis in Cancer)
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Open AccessReview Recent Advances in the Management of Cancer-Associated Thrombosis: New Hopes but New Challenges
Received: 15 December 2018 / Revised: 31 December 2018 / Accepted: 8 January 2019 / Published: 10 January 2019
Cited by 2 | PDF Full-text (269 KB) | HTML Full-text | XML Full-text
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue The Role of Thrombosis and Haemostasis in Cancer)
Open AccessReview Endothelial Protein C Receptor (EPCR), Protease Activated Receptor-1 (PAR-1) and Their Interplay in Cancer Growth and Metastatic Dissemination
Received: 7 December 2018 / Revised: 28 December 2018 / Accepted: 28 December 2018 / Published: 8 January 2019
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Abstract
Endothelial protein C receptor (EPCR) and protease activated receptor 1 (PAR-1) by themselves play important role in cancer growth and dissemination. Moreover, interactions between the two receptors are essential for tumor progression. EPCR is a cell surface transmembrane glycoprotein localized predominantly on endothelial [...] Read more.
Endothelial protein C receptor (EPCR) and protease activated receptor 1 (PAR-1) by themselves play important role in cancer growth and dissemination. Moreover, interactions between the two receptors are essential for tumor progression. EPCR is a cell surface transmembrane glycoprotein localized predominantly on endothelial cells (ECs). It is a vital component of the activated protein C (APC)—mediated anticoagulant and cytoprotective signaling cascade. PAR-1, which belongs to a family of G protein–coupled cell surface receptors, is also widely distributed on endothelial and blood cells, where it plays a critical role in hemostasis. Both EPCR and PAR-1, generally considered coagulation-related receptors, are implicated in carcinogenesis and dissemination of diverse tumor types, and their expression correlates with clinical outcome of cancer patients. Existing data explain some mechanisms by which EPCR/PAR-1 affects cancer growth and metastasis; however, the exact molecular basis of cancer invasion associated with the signaling is still obscure. Here, we discuss the role of EPCR and PAR-1 reciprocal interactions in cancer progression as well as potential therapeutic options targeted specifically to interact with EPCR/PAR-1-induced signaling in cancer patients. Full article
(This article belongs to the Special Issue The Role of Thrombosis and Haemostasis in Cancer)
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Open AccessReview Treatment and Prevention of Cancer-Associated Thrombosis in Frail Patients: Tailored Management
Received: 23 November 2018 / Revised: 22 December 2018 / Accepted: 28 December 2018 / Published: 7 January 2019
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Abstract
Advanced age is one of the major determinants of frailty in patients with cancer-associated thrombosis. However, multiple other factors contribute to frailty in these patients. The identification of frailty in patients with cancer-associated thrombosis is critical as it influences the complexity of the [...] Read more.
Advanced age is one of the major determinants of frailty in patients with cancer-associated thrombosis. However, multiple other factors contribute to frailty in these patients. The identification of frailty in patients with cancer-associated thrombosis is critical as it influences the complexity of the anticoagulant treatment in this population at high risk of venous thromboembolism and bleeding. Factors that contribute to frailty in patients with cancer-associated thrombosis include age, type of cancer, comorbidities such as chronic kidney disease, poly-pharmacotherapy, treatment compliance, cognitive impairment, anemia, thrombocytopenia, mobility, nutritional status, Eastern Cooperative Oncology Group grade, risk of falls, and reduced life expectancy. In the absence of specific clinical studies current anticoagulant treatment guidelines for the management are not fully applicable to frail patients with cancer. The anticoagulant treatment should therefore benefit from a tailored approach based on an algorithm that takes into account the specificities of the malignant disease. Full article
(This article belongs to the Special Issue The Role of Thrombosis and Haemostasis in Cancer)
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Open AccessReview Direct Oral Anticoagulant Drugs: On the Treatment of Cancer-Related Venous Thromboembolism and their Potential Anti-Neoplastic Effect
Received: 30 November 2018 / Revised: 24 December 2018 / Accepted: 28 December 2018 / Published: 5 January 2019
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Abstract
Cancer patients develop a hypercoagulable state with a four- to seven-fold higher thromboembolic risk compared to non-cancer patients. Thromboembolic events can precede the diagnosis of cancer, but they more often occur at diagnosis or during treatment. After malignancy itself, they represent the second [...] Read more.
Cancer patients develop a hypercoagulable state with a four- to seven-fold higher thromboembolic risk compared to non-cancer patients. Thromboembolic events can precede the diagnosis of cancer, but they more often occur at diagnosis or during treatment. After malignancy itself, they represent the second cause of death. Low molecular weight heparins are the backbone of the treatment of cancer-associated thromboembolism. This treatment paradigm is possibly changing, as direct oral anticoagulants (DOACs) may prove to be an alternative therapeutic option. The currently available DOACs were approved during the first and second decades of the 21st century for various clinical indications. Three molecules (apixaban, edoxaban and rivaroxaban) are targeting the activated factor X and one (dabigatran) is directed against the activated factor II, thrombin. The major trials analyzed the effect of these agents in the general population, with only a small proportion of cancer patients. Two published and several ongoing studies are specifically investigating the use of DOACs in cancer-associated thromboembolism. This article will review the current available literature on the use of DOACs in cancer patients. Furthermore, we will discuss published data suggesting potential anti-cancer actions exerted by non-anticoagulant effects of DOACs. As soon as more prospective data becomes available, DOACs are likely to be considered as a potential new therapeutic option in the armamentarium for patients suffering of cancer-associated thromboembolism. Full article
(This article belongs to the Special Issue The Role of Thrombosis and Haemostasis in Cancer)
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Open AccessReview Cancer-Associated Thrombosis in Cirrhotic Patients with Hepatocellular Carcinoma
Cancers 2018, 10(11), 450; https://doi.org/10.3390/cancers10110450
Received: 15 October 2018 / Revised: 2 November 2018 / Accepted: 13 November 2018 / Published: 16 November 2018
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Abstract
It is common knowledge that cancer patients are more prone to develop venous thromboembolic complications (VTE). It is therefore not surprising that patients with hepatocellular carcinoma (HCC) present with a significant risk of VTE, with the portal vein being the most frequent site [...] Read more.
It is common knowledge that cancer patients are more prone to develop venous thromboembolic complications (VTE). It is therefore not surprising that patients with hepatocellular carcinoma (HCC) present with a significant risk of VTE, with the portal vein being the most frequent site (PVT). However, patients with HCC are peculiar as both cancer and liver cirrhosis are conditions that can perturb the hemostatic balance towards a prothrombotic state. Because HCC-related hypercoagulability is not clarified at all, the aim of the present review is to summarize the currently available knowledge on epidemiology and pathogenesis of non-malignant thrombotic complications in patients with liver cirrhosis and HCC. They are at increased risk to develop both PVT and non-splanchnic VTE, indicating that both local and systemic factors can foster the development of site-specific thrombosis. Recent studies have suggested multiple and often interrelated mechanisms through which HCC can tip the hemostatic balance of liver cirrhosis towards hypercoagulability. Described mechanisms include increased fibrinogen concentration/polymerization, thrombocytosis, and release of tissue factor-expressing extracellular vesicles. Currently, there are no specific guidelines on the use of thromboprophylaxis in this unique population. There is the urgent need of prospective studies assessing which patients have the highest prothrombotic profile and would therefore benefit from early thromboprophylaxis. Full article
(This article belongs to the Special Issue The Role of Thrombosis and Haemostasis in Cancer)
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Open AccessReview Impacts of Cancer on Platelet Production, Activation and Education and Mechanisms of Cancer-Associated Thrombosis
Cancers 2018, 10(11), 441; https://doi.org/10.3390/cancers10110441
Received: 30 September 2018 / Revised: 31 October 2018 / Accepted: 10 November 2018 / Published: 14 November 2018
Cited by 3 | PDF Full-text (1985 KB) | HTML Full-text | XML Full-text
Abstract
Platelets are small anucleate cells that are traditionally described as the major effectors of hemostasis and thrombosis. However, increasing evidence indicates that platelets play several roles in the progression of malignancies and in cancer-associated thrombosis. A notable cross-communication exists between platelets and cancer [...] Read more.
Platelets are small anucleate cells that are traditionally described as the major effectors of hemostasis and thrombosis. However, increasing evidence indicates that platelets play several roles in the progression of malignancies and in cancer-associated thrombosis. A notable cross-communication exists between platelets and cancer cells. On one hand, cancer can “educate” platelets, influencing their RNA profiles, the numbers of circulating platelets and their activation states. On the other hand, tumor-educated platelets contain a plethora of active biomolecules, including platelet-specific and circulating ingested biomolecules, that are released upon platelet activation and participate in the progression of malignancy. The numerous mechanisms by which the primary tumor induces the production, activation and aggregation of platelets (also known as tumor cell induced platelet aggregation, or TCIPA) are directly related to the pro-thrombotic state of cancer patients. Moreover, the activation of platelets is critical for tumor growth and successful metastatic outbreak. The development or use of existing drugs targeting the activation of platelets, adhesive proteins responsible for cancer cell-platelet interactions and platelet agonists should be used to reduce cancer-associated thrombosis and tumor progression. Full article
(This article belongs to the Special Issue The Role of Thrombosis and Haemostasis in Cancer)
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Open AccessReview Cancer-Associated Thrombosis: An Overview of Mechanisms, Risk Factors, and Treatment
Cancers 2018, 10(10), 380; https://doi.org/10.3390/cancers10100380
Received: 11 September 2018 / Revised: 4 October 2018 / Accepted: 7 October 2018 / Published: 11 October 2018
Cited by 3 | PDF Full-text (996 KB) | HTML Full-text | XML Full-text
Abstract
Cancer-associated thrombosis is a major cause of mortality in cancer patients, the most common type being venous thromboembolism (VTE). Several risk factors for developing VTE also coexist with cancer patients, such as chemotherapy and immobilisation, contributing to the increased risk cancer patients have [...] Read more.
Cancer-associated thrombosis is a major cause of mortality in cancer patients, the most common type being venous thromboembolism (VTE). Several risk factors for developing VTE also coexist with cancer patients, such as chemotherapy and immobilisation, contributing to the increased risk cancer patients have of developing VTE compared with non-cancer patients. Cancer cells are capable of activating the coagulation cascade and other prothrombotic properties of host cells, and many anticancer treatments themselves are being described as additional mechanisms for promoting VTE. This review will give an overview of the main thrombotic complications in cancer patients and outline the risk factors for cancer patients developing cancer-associated thrombosis, focusing on VTE as it is the most common complication observed in cancer patients. The multiple mechanisms involved in cancer-associated thrombosis, including the role of anticancer drugs, and a brief outline of the current treatment for cancer-associated thrombosis will also be discussed. Full article
(This article belongs to the Special Issue The Role of Thrombosis and Haemostasis in Cancer)
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Open AccessReview The Role of Direct Oral Anticoagulants in Treatment of Cancer-Associated Thrombosis
Cancers 2018, 10(8), 271; https://doi.org/10.3390/cancers10080271
Received: 3 July 2018 / Revised: 7 August 2018 / Accepted: 13 August 2018 / Published: 15 August 2018
Cited by 2 | PDF Full-text (257 KB) | HTML Full-text | XML Full-text
Abstract
Venous thromboembolism (VTE) complicates the clinical course of approximately 5–10% of all cancer patients. Anticoagulation of the cancer patient often presents unique challenges as these patients have both a higher risk of recurrent VTE and a higher risk of bleeding than patients without [...] Read more.
Venous thromboembolism (VTE) complicates the clinical course of approximately 5–10% of all cancer patients. Anticoagulation of the cancer patient often presents unique challenges as these patients have both a higher risk of recurrent VTE and a higher risk of bleeding than patients without cancer. Although low molecular weight heparins (LMWH) are the standard of care for the management of cancer-associated VTE, their use requires once or twice daily subcutaneous injections, which can be a significant burden for many cancer patients who often require a long duration of anticoagulation. The direct oral anticoagulants (DOACs) are attractive options for patients with malignancy. DOACs offer immediate onset of action and short half-lives, properties similar to LMWH, but the oral route of administration is a significant advantage. Given the higher risks of recurrent VTE and bleeding, there has been concern about the efficacy and safety of DOACs in this patient population. Data are now emerging for the use of DOACs in the cancer patient population from dedicated clinical trials. While recently published data suggest that DOACs hold promise for the treatment of cancer associated VTE, additional studies are needed to establish DOACs as the standard-of-care treatment. Many such studies are currently underway. The available data for the use of DOACs in the treatment of cancer-associated VTE will be reviewed, focusing on efficacy, safety, and other considerations relevant to the cancer patient. Full article
(This article belongs to the Special Issue The Role of Thrombosis and Haemostasis in Cancer)
Open AccessFeature PaperReview Antithrombotic Agents and Cancer
Cancers 2018, 10(8), 253; https://doi.org/10.3390/cancers10080253
Received: 2 July 2018 / Revised: 27 July 2018 / Accepted: 28 July 2018 / Published: 31 July 2018
Cited by 2 | PDF Full-text (906 KB) | HTML Full-text | XML Full-text
Abstract
Platelet activation is the first response to tissue damage and, if unrestrained, may promote chronic inflammation-related cancer, mainly through the release of soluble factors and vesicles that are rich in genetic materials and proteins. Platelets also sustain cancer cell invasion and metastasis formation [...] Read more.
Platelet activation is the first response to tissue damage and, if unrestrained, may promote chronic inflammation-related cancer, mainly through the release of soluble factors and vesicles that are rich in genetic materials and proteins. Platelets also sustain cancer cell invasion and metastasis formation by fostering the development of the epithelial-mesenchymal transition phenotype, cancer cell survival in the bloodstream and arrest/extravasation at the endothelium. Furthermore, platelets contribute to tumor escape from immune elimination. These findings provide the rationale for the use of antithrombotic agents in the prevention of cancer development and the reduction of metastatic spread and mortality. Among them, low-dose aspirin has been extensively evaluated in both preclinical and clinical studies. The lines of evidence have been considered appropriate to recommend the use of low-dose aspirin for primary prevention of cardiovascular disease and colorectal cancer by the USA. Preventive Services Task Force. However, two questions are still open: (i) the efficacy of aspirin as an anticancer agent shared by other antiplatelet agents, such as clopidogrel; (ii) the beneficial effect of aspirin improved at higher doses or by the co-administration of clopidogrel. This review discusses the latest updates regarding the mechanisms by which platelets promote cancer and the efficacy of antiplatelet agents. Full article
(This article belongs to the Special Issue The Role of Thrombosis and Haemostasis in Cancer)
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Open AccessReview Bone Marrow Defects and Platelet Function: A Focus on MDS and CLL
Cancers 2018, 10(5), 147; https://doi.org/10.3390/cancers10050147
Received: 20 April 2018 / Revised: 11 May 2018 / Accepted: 16 May 2018 / Published: 18 May 2018
Cited by 2 | PDF Full-text (521 KB) | HTML Full-text | XML Full-text
Abstract
The bloodstream typically contains >500 billion anucleate circulating platelets, derived from megakaryocytes in the bone marrow. This review will focus on two interesting aspects of bone marrow dysfunction and how this impacts on the quality of circulating platelets. In this regard, although megakaryocytes [...] Read more.
The bloodstream typically contains >500 billion anucleate circulating platelets, derived from megakaryocytes in the bone marrow. This review will focus on two interesting aspects of bone marrow dysfunction and how this impacts on the quality of circulating platelets. In this regard, although megakaryocytes are from the myeloid lineage leading to granulocytes (including neutrophils), erythrocytes, and megakaryocytes/platelets, recent evidence has shown that defects in the lymphoid lineage leading to B cells, T cells, and natural killer (NK) cells also result in abnormal circulating platelets. Current evidence is limited regarding whether this latter phenomenon might potentially arise from (a) some form of as-yet-undetected defect common to both lineages; (b) adverse interactions occurring between cells of different lineages within the bone marrow environment; and/or (c) unknown disease-related factor(s) affecting circulating platelet receptor expression/function after their release from megakaryocytes. Understanding the mechanisms underlying how both myeloid and lymphoid lineage bone marrow defects lead to dysfunction of circulating platelets is significant because of the potential diagnostic and predictive value of peripheral platelet analysis for bone marrow disease progression, the additional potential effects of new anti-cancer drugs on platelet function, and the critical role platelets play in regulation of bleeding risk, inflammation, and innate immunity. Full article
(This article belongs to the Special Issue The Role of Thrombosis and Haemostasis in Cancer)
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