Abstract

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.

Highlights

  • With physicians being aware of the increased risk of thromboembolic complications in cancer patients and the high impact of these events on quality of life, morbidity, and mortality as well as the connected economic burden, studies on the role of primary pharmacological prophylaxis in different populations of cancer patients started more than 20 years ago, and some more recent studies are ongoing.A venous thrombotic/thromboembolic event (VTE) is a frequent and serious complication of cancer

  • According to a systematic meta-analysis of more than 300 hospitalized cancer patients, out of a subgroup of almost 5000 patients from three randomized trials, prophylactic anticoagulation with low-molecular-weight heparins (LMWH) or fondaparinux, as compared to placebo, was unable to provide a benefit in VTE reduction [16]

  • For mobile cancer patients admitted to the hospital for non-surgical diagnostic purposes or for complex anti-cancer therapies, the indication for thromboprophylaxis should follow the recommendations for outpatients, since the Khorana score (KS, Table 2) has shown validity in predicting VTE development in hospitalized patients as well [36]

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Summary

Introduction

With physicians being aware of the increased risk of thromboembolic complications in cancer patients and the high impact of these events on quality of life, morbidity, and mortality as well as the connected economic burden, studies on the role of primary pharmacological prophylaxis in different populations of cancer patients started more than 20 years ago, and some more recent studies are ongoing.A venous thrombotic/thromboembolic event (VTE) is a frequent and serious complication of cancer. VTEs in cancer patients cause significant morbidity and mortality [1], they are a ‘signum malum’, indicating an adverse prognosis of the cancer itself [2,3] This negative prognostic effect has been shown for all common cancer types, e.g., gastrointestinal cancer [4], lung cancer [5,6], breast cancer [7] prostate cancer [8], and hematological malignancies [9]. Besides direct adverse effects, VTEs may cause delays or even discontinuation of cancer treatment with a negative impact on prognosis Despite these well-recognized interactions, clinical trials have failed to demonstrate a survival benefit for primary thromboprophylaxis in cancer patients generally [17,18,19,20]. Besides recommendations after each paragraph, all recommendations are summarized in a comprehensive table in the supplement (Supplementary Materials Table S1)

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