Recent Advances in the Management of Cancer-Associated Thrombosis: New Hopes but New Challenges

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.

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The Role of Direct Oral Anticoagulants in Treatment of Cancer-Associated Thrombosis

Cancers ◽

10.3390/cancers10080271 ◽

2018 ◽

Vol 10 (8) ◽

pp. 271 ◽

Cited By ~ 20

Author(s):

Hanny Al-Samkari ◽

Jean Connors

Keyword(s):

Cancer Patient ◽

Cancer Patients ◽

Patient Population ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Population Data ◽

Standard Of Care ◽

Published Data ◽

Onset Of Action ◽

Recurrent Vte

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.

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Current Recommendations for the Management of Cancer-Associated Venous Thromboembolism

Journal Of Cardiovascular Emergencies ◽

10.2478/jce-2021-0009 ◽

2021 ◽

Vol 7 (2) ◽

pp. 27-38

Author(s):

Katalin Makó

Keyword(s):

Risk Factors ◽

Venous Thromboembolism ◽

Cancer Patients ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Bleeding Risk ◽

Term Treatment ◽

Long Term Treatment ◽

High Bleeding Risk ◽

Cancer Associated Thrombosis

Abstract Cancer-associated thrombosis (CAT) is a major cause of death in oncological patients. The mechanisms of thrombogenesis in cancer patients are not fully established, and it seems to be multifactorial in origin. Also, several risk factors for venous thromboembolism (VTE) are present in these patients such as tumor site, stage, histology of cancer, chemotherapy, surgery, and immobilization. Anticoagulant treatment in CAT is challenging because of high bleeding risk during treatment and recurrence of VTE. Current major guidelines recommend low molecular weight heparins (LMWHs) for early and long-term treatment of VTE in cancer patients. In the past years, direct oral anticoagulants (DOACs) are recommended as potential treatment option for VTE and have recently been proposed as a new option for treating CAT. This manuscript will give a short overview of risk factors involved in the development of CAT and a summary on the recent recommendations and guidelines for treatment of VTE in patients with malignancies, discussing also some special clinical situations (e.g. renal impairment, catheter-related thrombosis, and thrombocytopenia).

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Direct oral anticoagulants for the treatment of cancer-associated venous thromboembolism

Phlebologie ◽

10.1055/s-0038-1625439 ◽

2017 ◽

Vol 46 (06) ◽

pp. 340-351

Author(s):

M. Voigtlaender ◽

F. Langer

Keyword(s):

Venous Thromboembolism ◽

Cancer Patients ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Treatment Phase ◽

Standard Of Care ◽

Longterm Treatment ◽

Increased Risk ◽

Direct Head

SummaryCancer patients with venous thromboembolism (VTE) are at increased risk for both bleeding and VTE recurrence. Anticoagulation with low-molecular-weight heparin (LMWH) is the standard of care during the initial and longterm treatment phase (i.e. during the first 3–6 months of therapy) based on its overall beneficial safety and efficacy profile compared to vitamin K antagonists (VKAs). The direct oral anticoagulants (DOACs) rivaroxaban, apixaban, edoxaban, and dabigatran are approved for the treatment of acute VTE, and the combined six phase-3 trials have included > 1 500 patients with active cancer, as defined by variable selection criteria. Subgroup analyses of these patients, either pooled or separately reported, suggest that DOACs could be a safe and efficacious alternative to VKA therapy for the treatment of cancer-associated VTE. However, the populations of cancer patients included in the DOAC and LMWH trials are not comparable with regard to mortality and VTE risk, and no specific data from direct head-to-head comparisons of DOACs with LMWHs are currently available. The use of DOACs for the management of VTE in cancer is thus not recommended by clinical practice guidelines.

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The Prevention and treatment of cancer-associated thrombosis

Current Oncology ◽

10.3747/co.27.6873 ◽

2020 ◽

Vol 27 (5) ◽

Author(s):

S. Ng ◽

M. Carrier

Keyword(s):

Low Molecular Weight Heparin ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Anticoagulation Therapy ◽

Standard Of Care ◽

Low Molecular Weight ◽

Safe Alternative ◽

Patients With Cancer ◽

Increased Risk ◽

Cancer Associated Thrombosis

Cancer is a hypercoagulable state with an associated increased risk of venous thromboembolism (vte) that is further amplified in individuals who undergo chemotherapy. Compared with patients having cancer alone or vte alone, patients who develop cancer-associated vte have a significantly poorer prognosis. The risks of recurrent vte despite appropriate anticoagulation therapy and of bleeding are also higher in patients with cancer than in those without. For those reasons, the prevention and appropriate management of cancer-associated thrombosis is of paramount importance. Although low-molecular-weight heparin has been the standard of care for the prevention and treatment of cancer-associated thrombosis, direct oral anticoagulants are increasingly being adopted as an effective and safe alternative.

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Direct oral anticoagulants and digestive bleeding: therapeutic management and preventive measures

Therapeutic Advances in Gastroenterology ◽

10.1177/1756283x17702092 ◽

2017 ◽

Vol 10 (6) ◽

pp. 495-505 ◽

Cited By ~ 15

Author(s):

David Deutsch ◽

Christian Boustière ◽

Emile Ferrari ◽

Pierre Albaladejo ◽

Pierre-Emmanuel Morange ◽

...

Keyword(s):

Renal Function ◽

Gastrointestinal Bleeding ◽

Preventive Measures ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Bleeding Risk ◽

Rapid Onset ◽

Treatment Monitoring ◽

Onset Of Action

The use of direct oral anticoagulants (DOACs) was an important step forward in the management of atrial fibrillation and venous thromboembolism (VTE). The DOACs, anti-IIa for dabigatran and anti-Xa for rivaroxaban, apixaban and edoxaban, all have a rapid onset of action and a short half life. There is no need for routine hemostasis testing for treatment monitoring of a DOAC. Compared with vitamin K antagonists (VKAs), DOACs may increase the risk of gastrointestinal bleeding (relative risk 1.25). Withholding the DOAC treatment, evaluating the time of the last intake and estimating the patient’s renal function are the first steps in the management of gastrointestinal bleeding. For patients without impaired renal function, achieving low coagulation takes around 24 h after the last intake of a DOAC. The use of DOAC antagonists will be helpful in controlling bleeding in the most severe and urgent situations. Idarucizumab is available for clinical use for dabigatran and andexanet is currently being reviewed by drug agencies for rivaroxaban, apixaban and edoxaban. It is important to assess the bleeding risk associated with the planned procedure, and the patient’s renal function before withholding DOAC therapy for a scheduled intervention. It is mandatory to strengthen the local hemostasis strategies in DOAC-treated patients undergoing a therapeutic endoscopic procedure. Resuming or not resuming anticoagulation with a DOAC after bleeding or a risky procedure depends on the thrombotic and bleeding risk as well as the procedure involved. This discussion should always involve the cardiologist and decisions should be taken by a pluridisciplinary team.

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Practical Implementation of Anticoagulation Strategy for Patients Undergoing Cardioversion of Atrial Fibrillation

Arrhythmia & Electrophysiology Review ◽

10.15420/aer.2017:3:2 ◽

2017 ◽

Vol 6 (2) ◽

pp. 50 ◽

Cited By ~ 4

Author(s):

Andreas Goette ◽

Hein Heidbuchel ◽

◽

Keyword(s):

Randomised Controlled Trials ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Rapid Onset ◽

Practical Implementation ◽

Controlled Trials ◽

Efficacy And Safety ◽

Onset Of Action ◽

Randomised Controlled ◽

Post Hoc

Anticoagulation is routinely prescribed to patients with persistent AF before cardioversion to reduce the risk of thromboembolic events. As direct oral anticoagulants (DOACs) have a rapid onset of action, a consistent anticoagulant effect, if taken correctly, and do not need monitoring or dose adjustments, there is considerable interest in their use for patients with AF undergoing cardioversion. Post-hoc analyses show that DOACs are safe to use prior to and following cardioversion. In addition, two randomised controlled trials, X-VeRT and ENSURE-AF, have demonstrated the efficacy and safety of the DOACs rivaroxaban and edoxaban, respectively, in this setting. The use of DOACs allows cardioversions to be performed promptly and reduces the number of cancelled procedures compared with the use of warfarin.

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Recent advances in the treatment and prevention of venous thromboembolism in cancer patients: role of the direct oral anticoagulants and their unique challenges

F1000Research ◽

10.12688/f1000research.18673.1 ◽

2019 ◽

Vol 8 ◽

pp. 974 ◽

Cited By ~ 3

Author(s):

Dominique Farge ◽

Corinne Frere

Keyword(s):

Venous Thromboembolism ◽

Cancer Patients ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Patient Characteristics ◽

Primary Prophylaxis ◽

Disease Stage ◽

Vte Prophylaxis ◽

Patients With Cancer ◽

Increased Risk

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.

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Safety of New Oral Anticoagulants for Patients with Chronic Kidney Disease

Current Pharmaceutical Design ◽

10.2174/1381612825666190130144051 ◽

2019 ◽

Vol 24 (38) ◽

pp. 4505-4510 ◽

Cited By ~ 1

Author(s):

Krasiński Zbigniew ◽

Stępak Hubert ◽

Jawień Andrzej ◽

Stanisic Michal

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Daily Practice ◽

Rapid Onset ◽

Onset Of Action ◽

Reasonable Choice ◽

Moderate Chronic Kidney Disease

In daily practice, chemical substances called “direct oral anticoagulants” or DOACs are more convenient to administer when set beside vitamin K antagonists (VKA) due to improved pharmacologic properties, fewer drug interactions and rapid onset of action. The objective of this review was to assess whether DOACs are the alternative for VKA in subjects with mild-to-moderate chronic kidney disease (CKD). An analysis of current DOAC trials and studies was performed focusing on subjects with CKD. This review concludes that although DOACS are not recommended in the course of advanced chronic kidney disease (CrCl<30mL/min) or during dialysis, DOACS are a reasonable choice for individuals with mild to moderate CKD.

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Retrospective Review of Prescribing Patterns in Cancer-Associated Thrombosis: A Single Center Experience in Edmonton, Alberta, Canada

Clinical and Applied Thrombosis/Hemostasis ◽

10.1177/1076029620975489 ◽

2021 ◽

Vol 27 ◽

pp. 107602962097548

Author(s):

Hannah Kaliel ◽

Meghan Mior ◽

Steven Quan ◽

Sunita Ghosh ◽

Cynthia Wu ◽

...

Keyword(s):

Retrospective Review ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Chronic Phase ◽

Standard Of Care ◽

Prescribing Patterns ◽

Real World Data ◽

Cancer Trial ◽

Single Center Experience ◽

Cancer Associated Thrombosis

Low molecular weight heparin (LMWH) is the standard of care for treating cancer-associated thrombosis (CAT), although new evidence for direct oral anticoagulants (DOACs) supports use in specific cancer populations. In this retrospective review at a specialty CAT clinic from 2016 to 2019, we report the use of anticoagulants (LMWH, DOACs, warfarin, anticoagulant class change) in the acute and chronic phases of CAT and compare use before/after publication of the Hokusai-VTE Cancer trial. Death, venous thromboembolism (VTE) recurrence and bleeding was also reported. Of the 221 included, median age was 69 years, with 57.5% having metastatic disease. In the acute phase, 80.1% were prescribed LMWH, 4.1% DOAC, and 14.5% had an anticoagulant class change (LMWH to DOAC; 78.1%). In the chronic phase, 35.8% were prescribed LMWH, 11.3% DOAC, and 42.9% had an anticoagulant class change (LMWH to DOAC; 90.1%). Use of DOACs in the acute and chronic phase prior to the Hokusai-VTE trial was 1.0% and 2.0%, respectively, and following publication was 6.8% and 19.6%. Death occurred for 22.6% patients, recurrent VTE in 7.2%, and bleeding in 5.0%. DOAC use is increasing with time; real-world data may help to guide optimization of the care of complex patients.

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Direct oral anticoagulants for the treatment of cancer-associated venous thromboembolism

Hämostaseologie ◽

10.5482/hamo-16-09-0036 ◽

2017 ◽

Vol 37 (04) ◽

pp. 241-255 ◽

Cited By ~ 4

Author(s):

Minna Voigtlaender ◽

Florian Langer

Keyword(s):

Venous Thromboembolism ◽

Cancer Patients ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Treatment Phase ◽

Standard Of Care ◽

Longterm Treatment ◽

Increased Risk ◽

Direct Head

SummaryCancer patients with venous thromboembolism (VTE) are at increased risk for both bleeding and VTE recurrence. Anticoagulation with low-molecular-weight heparin (LMWH) is the standard of care during the initial and longterm treatment phase (i.e. during the first 3 – 6 months of therapy) based on its overall beneficial safety and efficacy profile compared to vitamin K antagonists (VKAs). The direct oral anticoagulants (DOACs) rivaroxaban, apixaban, edoxaban, and dabigatran are approved for the treatment of acute VTE, and the combined six phase-3 trials have included > 1500 patients with active cancer, as defined by variable selection criteria. Subgroup analyses of these patients, either pooled or separately reported, suggest that DOACs could be a safe and efficacious alternative to VKA therapy for the treatment of cancer-associated VTE. However, the populations of cancer patients included in the DOAC and LMWH trials are not comparable with regard to mortality and VTE risk, and no specific data from direct head-to-head comparisons of DOACs with LMWHs are currently available. The use of DOACs for the management of VTE in cancer is thus not recommended by clinical practice guidelines.

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