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Beschreibung

Ever since the association between cancer and thrombosis was reported by Jean-Baptiste Bouillaud in the early 19th century, cancer-associated thrombosis has remained a challenging domain of cancer management. Thrombosis can at times be a lead to cancer diagnosis, while it often complicates medical situations as a coexisting disorder. In this handbook, the contributors have compiled comprehensive information on the subject to provide the reader a comprehensive review of current medical literature and guidelines for cancer-associated thrombosis.

Key Features
-clinically oriented text for application in healthcare settings
-current, evidence-based literature reviews and references
-includes guidelines on VTE prophylaxis, heparin effects and more
-includes information about special cases

Thrombosis in Cancer: A Medical Professional's Guide to Cancer Associated Thrombosis is an informative handbook for a broad range of readers in medicine, including generalists, residents, and graduate-level trainees.

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Veröffentlichungsjahr: 2021

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Table of Contents
Welcome
Table of Content
Title
BENTHAM SCIENCE PUBLISHERS LTD.
End User License Agreement (for non-institutional, personal use)
Usage Rules:
Disclaimer:
Limitation of Liability:
General:
FOREWORD
PREFACE
List of Contributors
Overview of Cancer-Associated Thrombosis
Abstract
INTRODUCTION
EPIDEMIOLOGY
PROGNOSIS AND IMPACT OF VTE IN CANCER PATIENTS
CONSENT FOR PUBLICATION
CONFLICT OF INTEREST
ACKNOWLEDGEMENTS
REFERENCES
Pathophysiology and Risk Factors for Cancer-Associated Thrombosis
Abstract
PATHOPHYSIOLOGY
RISK FACTORS
Tumor Related Factors
Treatment-Related Factors
Surgery
Hospitalization
Chemotherapy, Hormonal Therapy, and Radiotherapy
Supportive Therapy
Patient-Related Factors
BIOMARKERS
RISK MODELS
CONSENT FOR PUBLICATION
CONFLICT OF INTEREST
ACKNOWLEDGEMENTS
REFERENCES
Impact of Venous Thromboembolism on Cancer Survival
Abstract
BACKGROUND
INCIDENCE
MORTALITY
VTE RECURRENCE
EFFECT OF ANTICOAGULATION IN CANCER
CONCLUSION
CONSENT FOR PUBLICATION
CONFLICT OF INTEREST
ACKNOWLEDGEMENTS
REFERENCES
Occult Cancer Workup in Idiopathic Venous Thromboembolism
Abstract
INTRODUCTION
CONSENT FOR PUBLICATION
CONFLICT OF INTEREST
ACKNOWLEDGEMENTS
REFERENCES
Chemotherapy Induced Thrombosis
Abstract
INTRODUCTION
PATHOPHYSIOLOGY
PROPHYLAXIS DURING CHEMOTHERAPY
CONSENT FOR PUBLICATION
CONFLICT OF INTEREST
ACKNOWLEDGEMENTS
REFERENCES
Catheter-Related Thrombosis in Cancer
Abstract
INTRODUCTION
EPIDEMIOLOGY AND RISK FACTORS
PATHOPHYSIOLOGY AND TYPES OF CRT
Pericatheter Sheath or Fibrin Sleeve
Intraluminal Clot
Mural Thrombus
Other Causes
CLINICAL PRESENTATION
DIAGNOSIS
TREATMENT
Removal of Catheter
Systemic Anticoagulation
Other Options
PREVENTION OF CRT IN CANCER PATIENTS
CONCLUSION
CONSENT FOR PUBLICATION
CONFLICT OF INTEREST
ACKNOWLEDGEMENTS
REFERENCES
Management of Cancer-Associated Thrombosis
Abstract
INTRODUCTION
INITIAL TREATMENT
Anticoagulants
Low Molecular Weight Heparin
Factor Xa Inhibitors
Unfractionated Heparin
Warfarin
LONG TERM MANAGEMENT
ROLE OF DIRECT ORAL ANTICOAGULANTS
FINANCIAL ASPECTS OF CHOOSING ANTICOAGULATION
MECHANICAL DEVICES
Inferior Vena Cava Filters
IMPACT ON SURVIVAL WITH ANTI-THROMBOTIC THERAPY
CONSENT FOR PUBLICATION
CONFLICT OF INTEREST
ACKNOWLEDGEMENTS
REFERENCES
Special Cases in Cancer-Associated Thrombosis
Abstract
INTRODUCTION
VTE and Thrombocytopenia
RECURRENT VTE
VTE in RENAL IMPAIRMENT
INCIDENTAL VTE IN CANCER
MYELOPROLIFERATIVE DISORDERS AND VTE
BONE MARROW TRANSPLANTATION AND VTE
CONSENT FOR PUBLICATION
CONFLICT OF INTEREST
ACKNOWLEDGEMENTS
REFERENCES
Antitumor Effects of Heparin
Abstract
INTRODUCTION
TYPES OF HEPARIN
Unfractionated Heparin
Low-Molecular-Weight Heparin
Butanoylated Heparin
EFFECTS OF HEPARIN ON TUMOR
Anti-Angiogenesis Effects
Antiproliferative Effects
Effects on Immune System
CONCLUSION
CONSENT FOR PUBLICATION
CONFLICT OF INTEREST
ACKNOWLEDGEMENTS
REFERENCES
VTE Prophylaxis
Abstract
INTRODUCTION
RISK STRATIFICATION
INPATIENT VTE PROPHYLAXIS
OUTPATIENT VTE PROPHYLAXIS
PERIOPERATIVE VTE PROPHYLAXIS
SOCIETY GUIDELINES
CONCLUSION
CONSENT FOR PUBLICATION
CONFLICT OF INTEREST
ACKNOWLEDGEMENTS

Thrombosis in Cancer:

A Medical Professional's Guide to Cancer Associated Thrombosis

Edited by

Supratik Rayamajhi

Prajwal Dhakal

Shiva Shrotriya
&
Nishraj Basnet
Department of Medicine,
Michigan State University,
USA

BENTHAM SCIENCE PUBLISHERS LTD.

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FOREWORD

I have been practicing academic clinical hematologist and oncologist for more than 20 years now. The author, Dr. Supratik Rayamajhi is my cherished colleague who I have known for the past decade. Most of the other authors are also my colleagues, and I have been an attending physician and mentor to some. I was thrilled to learn that the authors were busy writing a book on the topic of cancer-associated thrombosis. I anticipated the publication of this book and was rewarded with this opportunity to read it. The authors are all uniquely qualified to write on this important subject based on their experience, research, and insight into this topic. This is an area that I also have direct and almost daily medical experience with and can attest to this book’s current relevance and accuracy.

Why should you read this book? Well, are you someone that wants to get right to the point? Do you dislike long and verbose writing, that goes on and on? Are you someone that wants to keep current with the ever-changing medical literature? If so, then you are the right person for this book.

Cancer-associated thrombosis is a broad area but can be parsed into “bite-size” pieces that are easily “digestible” for consumption for the learner. The day of the giant 1,000-page medical tome is over. This is a book that highlights an important subject in an easy and to-the-point quick read that will not bore you with endless unnecessary detail. This book will turn you into a knowledgeable physician in this field in the shortest amount of time.

I have shown this book to other practicing hematologists and oncologists who have praised it. We all appreciate its accuracy and brevity without leaving anything of relevance out. I highly recommend this book to all eager students and practitioners of medicine, especially to anyone that wants to learn this topic from scratch or to those who might need a brief review.

I am the Director of the Michigan State University/McLaren hematology and oncology fellowship program and have made this text required reading for our fellows. Read this book and you will not be disappointed. You will have a whole world of cancer associate thrombosis knowledge right at your fingertips!

Borys Hrinczenko, MD, PhD Director Hematology and Oncology Fellowship Program Division of Hematology and Oncology Michigan State University USA

PREFACE

Cancer and Thrombosis are interrelated. Their relationship adds complexity to the already challenging domain of cancer management. Thrombosis can at times be a lead to cancer diagnosis, while it often complicates the situation as a co-existing disorder.

This book is a result of generalists’ endeavor to put together a rather simpler version of compilation, as it pertains to cancer-associated thrombosis (CAT). Our product is clinically oriented as compared to some in-depth basic science coverage of preexisting books on CAT. Our primary target audience naturally remains generalists and graduate-level trainees.

We have strived to stay current in terms of literature review. Specifically, we notice a paucity of evidence-based literature on thrombosis prophylaxis among cancer patients. We hope to infuse interest among our audience through an easy read of a complex entity that includes specific clinical situations and challenges, and hopefully, a palatable end-produce.

We do not have any conflict of interest to disclose during the preparation of this book.

Supratik Rayamajhi, MD Department of Medicine Michigan State University USA

List of Contributors

Alabacha Abdullah, Department of MedicineMichigan State UniversityMichiganUSAAbro Calvin, Department of MedicineMichigan State UniversityEast Lansing, MichiganUSARous Fawzi Abu, Department of MedicineMichigan State UniversityEast Lansing, MichiganUSAEnofe Ikponmwosa, Department of MedicineMichigan State UniversityEast Lansing, MichiganUSAElkhatib Layan A, Department of MedicineHenry Ford Hospital, DetroitMichiganUSAKarapetyan Lilit, Department of Hematology-OncologyUPMC Hillman Cancer CenterPAUSARai Manoj, Department of MedicineMichigan State UniversityEast Lansing, MichiganUSABasnet Nishraj, Department of MedicineMichigan State UniversityEast lansing, Michigan USAAlbanyan Omar, Department of MedicineMichigan State UniversityEast Lansing, MichiganUSAMosalem Osama, Department of MedicineMichigan State UniversityEast Lansing, MichiganUSADhakal Prajwal, Division of Oncology and Hematology, Department of Internal MedicineUniversity of Nebraska Medical Center UNMC, OmahaNebraskaUSAKandola Samanjit, Department of MedicineMichigan State UniversityEast Lansing, MichiganUSAGrigoryan Seda, Department of MedicineMichigan State UniversityMichiganUSAShrotriya Shiva, Department of MedicineMichigan State UniversityMichiganUSARayamajhi Supratik, Department of MedicineMichigan State UniversityMichiganUSA

Overview of Cancer-Associated Thrombosis

Prajwal Dhakal1,*,Nishraj Basnet2
1 Division of Oncology and Hematology, Department of Internal Medicine, University of Nebraska Medical Center UNMC, Omaha, Nebraska, USA
2 Department of Medicine, Michigan State University, East Lansing, Michigan, USA

Abstract

Ever since the association between cancer and thrombosis was reported in the early 19th century multiple studies have confirmed the relationship between cancer and thrombosis. Cancer patients, especially in the first few months after diagnosis and those with distant metastasis, have an elevated risk for VTE, and conversely, the risk of cancer diagnosis is high within the first 2 years of idiopathic VTE. VTE has an important impact on the prognosis of cancer patients. Thrombosis was the second leading cause of death (9.2%) after the cancer progression (70.9%) itself. The risks of recurrent VTE and bleeding are higher in patients with cancer-associated venous thrombosis than patients with venous thrombosis but without cancer.

Keywords: Anticoagulants, Cancer-associated thrombosis, Cancer costs, Cancer treatment, Coagulation in cancer, Hypercoagulability, Idiopathic VTE, Malignancy, Pulmonary embolism, Risks for VTE, Thrombosis, Trousseau syndrome, Venous thromboembolism, VTE prophylaxis, VTE treatment.
*Corresponding author Prajwal Dhakal: Division of Oncology and Hematology, Department of Internal Medicine, University of Nebraska Medical Center, USA; E-mail: [email protected]

INTRODUCTION

Thromboembolism, both venous and arterial, have been described in patients with cancer. While venous thromboembolism (VTE) in cancer includes deep vein thrombosis (DVT), pulmonary embolism (PE), and visceral thrombosis, arterial thrombosis includes myocardial infarction and stroke.

Historically, the association between cancer and thrombosis was reported early in the 19th century by Jean-Baptiste Bouillaud [1]. Later, in 1865, Armand Trousseau reported venous thrombosis in a case of gastric cancer [2]. Known as Trousseau’s syndrome, the term is nowadays used to describe VTE associated with any type of malignancy. Recent studies have confirmed those observations of the relationship between cancer and thrombosis from the 19th century. Cancer patients, especially

in the first few months after diagnosis and those with distant metastasis, have an elevated risk for VTE [3] and conversely, the risk of cancer diagnosis is high within the first 2 years of idiopathic VTE [4].

Despite many studies done in recent times, the exact pathophysiology of cancer and VTE is still unknown. Considerable overlap in cancer growth and coagulation pathways has been described along with a complex interaction between tumor cells, the hemostatic system, and the characteristics of the patient [5]. Additionally, the factors identified to elevate the risk of VTE such as hospital admissions, surgery, immobilization, chemotherapy, presence of catheters, and other comorbidities are present equally or even more in cancer patients than those without cancer [5-7]. Type and stage of the tumor, anti-cancer therapies, and other malignancy-associated factors are also associated with an increased absolute risk of VTE [8]. New risk factors, such as platelet and leukocyte count and tissue factor, have also been described with high VTE risk in cancer patients [9].

Evidence shows that VTE in cancer patients is associated with increased morbidity and mortality [10]. Additionally, cancer-associated thrombosis leads to increased utilization of health care resources and increased cost of care [11]. Cancer-associated thrombosis incurred higher overall all-cause inpatient costs, outpatient costs, and total health costs, leading to an average increase of all-cause costs of VTE by $30,538/patient [11]. Moreover, VTE may potentially interrupt or delay the management of cancer in addition to reducing the quality of life of cancer patients [12].

Despite recent studies and the development of clinical guidelines in the last few years, a substantial gap still exists in the knowledge of various aspects of cancer-associated thrombosis. As mentioned previously, the pathophysiology is not clear. Many risk factors have been identified but their impact in prophylaxis and treatment of VTE in cancer patients in addition to overall prognosis is still being studied. Moreover, there are major therapeutic challenges associated with VTE in cancer patients, that are further complicated by multiple cancer-related risk factors and comorbidities. Low molecular weight heparin and warfarin are recommended anticoagulants for treatment but there are many unanswered questions regarding the overall management of cancer-associated thrombosis, including the use of direct oral anticoagulants.

EPIDEMIOLOGY

Recent studies estimate that 20-30% of total VTE cases are associated with cancer [13-16]. The risk of VTE is increased by at 4- to 7-fold in cancer patients [17], with the risk increased to 28-fold in a certain type of malignancies [3]. The annual incidence of VTE is 0.5% in cancer patients, compared to 0.1% in the general population [18]. In a meta-analysis in 2012, Horsted et al. concluded that VTE occurred in greater than 1% of cancer patients each year, with wide variation dependent on the cancer type and time since diagnosis [19]. The overall risk of VTE was estimated to be 13 per 1,000 person-years (95% CI: 7-23) among average-risk patients. Patients with cancer of the pancreas, brain, and lungs had a higher risk of VTE than others, with brain cancer having the highest risk of VTE (200 per 1,000 person-years; 95% CI: 162-247). In patients with higher risk secondary to metastatic disease or receipt of high-risk treatments, the risk of VTE was 68 per 1,000 person-years (95% CI: 48-96) [19]. High risks of VTE have also been reported in lymphomas, myeloma, and kidney, stomach, ovarian, and bone cancer, with relatively low risks in patients with breast or prostate cancer [15]. The incidence of VTE increases from localized to regional to remote cancer in every cancer type [20]. Additionally, treatment modalities used for cancer substantially increase the VTE risk. The annual incidence rate of cancer patients treated with chemotherapy may range from 11-20% [21]. Similarly, surgery increases 90-day VTE risk by 2-fold in cancer patients in comparison to noncancer patients [22].

Over the years, the overall incidence of venous thrombosis in cancer patients has also increased gradually. The analysis of data from the US National Hospital Discharge Survey reported the increase in cumulative incidence of VTE from 1.5% in 1989 to 3.5% in 1999 [23]. In another study with linkage of four United Kingdom databases, the incidence of VTE in cancer patients was 19/1000 person-years in 2006 compared to 10.3/1000 person-years in 1997 [24]. Similarly, Khorana et al. reported a 36% increase in VTE among hospitalized neutropenic cancer patients between 1995 and 2002 [25].

The incidence of VTE is highest in the first few months after cancer diagnosis and gradually decreases thereafter. In the MEGA study, the risk for VTE was 54-fold higher in the first 3 months after diagnosis, declining to 14-fold after 3-12 months and 3.6 at 1–3 years after diagnosis [3]. The risk for VTE was close to those with no cancer after 10 years of diagnosis. Alcalay et al., in a retrospective analysis of colorectal cancer patients from the California Cancer Registry, reported the decrease in VTE incidence from 5.0/100 person-years in the first 6 months after a cancer diagnosis, to 1.4/100 person-years 6-12 months after a cancer diagnosis, and to 0.6/100 person-years 12-24 months after cancer diagnosis [26].

PROGNOSIS AND IMPACT OF VTE IN CANCER PATIENTS

VTE has an important impact on the prognosis of cancer patients. Thrombosis is a leading cause of death in patients with cancer [27]. An observational study was conducted by Khorana et al., with 4466 cancer patients. Among them, 141 patients died, and thrombosis was the second leading cause of death (9.2%) after the cancer progression (70.9%) itself [27]. Three-month mortality in cancer patients with venous thrombosis was much higher compared to venous thrombosis in patients without cancer (26% vs 4%, respectively) [28]. Similarly, another study reported a 5-fold higher 1-year case fatality rate in patients with cancer-associated venous thrombosis (63.4%; 95% CI: 54.5-71.8) than in venous thrombosis patients without cancer (12.6%; 95% CI: 10.1-15.5) [29]. Moreover, cancer patients with VTE had substantially higher in-hospital mortality than those without VTE (OR 2.01; p<0.0001), with a greater risk for death in metastatic disease (OR 2.06, p<0.0001) compared to those without metastasis [25]. Fatal pulmonary embolism has been reported 3 times more in cancer patients than in those without cancer [28].

Regarding complications, the risks of recurrent VTE and bleeding are higher in patients with cancer-associated venous thrombosis than patients with venous thrombosis but without cancer [28, 30, 31]. Prandoni et al. reported the cumulative incidence of recurrent VTE of 20.7% in cancer patients, compared with 6.8% among those without cancer (Hazard Ratio [HR] 3.2, 95% CI 1.9-5.4) [30]. Similarly, the incidence of major bleeding was 12.4% in cancer patients versus 4.9% in noncancer patients (HR 2.2, 95% CI, 1.2-4.1). Post-thrombotic syndrome and pulmonary hypertension have limited data regarding their impact on cancer patients with venous thrombosis.

CONSENT FOR PUBLICATION

Not applicable.

CONFLICT OF INTEREST

The author declares no conflict of interest, financial or otherwise.

ACKNOWLEDGEMENTS

Declared none.

REFERENCES

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Pathophysiology and Risk Factors for Cancer-Associated Thrombosis

Fawzi Abu Rous1,*,Layan A. Elkhatib2,Prajwal Dhakal3
1 Department of Medicine, Michigan State University, East Lansing, Michigan, USA
2 Department of Internal Medicine, Henry Ford Hospital, Detroit, Michigan, USA
3 Division of Oncology and Hematology, Department of Internal Medicine, University of Nebraska Medical Center UNMC, Omaha, Nebraska, USA

Abstract