Anticoagulants are the cornerstone of therapy for the treatment and prevention of cancer-associated thrombosis (CAT); factor Xa–inhibiting direct oral anticoagulants
Anticoagulant
Anticoagulants, commonly known as blood thinners, are chemical substances that prevent or reduce coagulation of blood, prolonging the clotting time. Some of them occur naturally in blood-eating animals such as leeches and mosquitoes, where they help keep the bite area unclotted long enough for the animal to obtain some blood. As a class of medications, anticoagulants are used in therapy for thr…
Full Answer
Should parenteral anticoagulation be used to treat established venous thromboembolism in cancer patients?
To date, at a guidance level, parenteral anticoagulation (e.g. LMWH) is preferred over oral anticoagulation in the treatment of established VTE in cancer patients with COVID-19 [ 52 ]. Cancer-associated venous thromboembolism is a concerning issue that increases both morbidity and mortality for patients with cancer.
What is cancer-associated venous thromboembolism (VTE)?
Cancer-associated venous thromboembolism (VTE) is a common and life-threatening condition in adult patients (≥18 years) with cancer [ 1 ]. Patients with cancer are four to seven times more likely to develop VTE than patients without cancer [ 2 ].
Is pre-emptive therapy for venous thromboembolism indicated in patients with cancer?
See other articles in PMC that cite the published article. Venous thromboembolism (VTE) is a major cause of morbidity and mortality among patients with cancer. Although much is known about the factors that contribute to VTE risk, pre-emptive therapy in high-risk populations is clearly indicated in only a few clinical situations.
Does cancer increase the risk of VTE recurrence?
Certain populations of patients with cancer have increased risk of VTE recurrence and/or bleeding and require special consideration during anticoagulant treatment of cancer-associated VTE.
How is VTE cancer treated?
For patients with cancer and VTE, the ASH guideline panel suggests DOAC (apixaban or rivaroxaban) or LMWH be used for initial treatment of VTE for patients with cancer (conditional recommendation, very low certainty in the evidence of effects ⊕◯◯◯).
Which medication has an indication for treatment of VTE in patients with cancer?
The guidelines currently recommend LMWH for 3-6 months as first-line treatment for patients with cancer-associated VTE.
What is the recommended length of treatment for VTE in patients with active cancer?
Duration of VTE treatment Because cancer is an ongoing risk factor for VTE, the guidelines of the American College of Chest Physicians (ACCP) and ASCO recommend indefinite VTE treatment “as long as the cancer is active” [25,51].
When can we stop anticoagulation in patients with cancer-associated thrombosis?
These patients had received a median duration of warfarin anticoagulation treatment of 79 days (interquartile range, 18-166), so the vast majority had stopped warfarin by 6 months. A number of clinical features have been identified to correlate with a higher risk of recurrent cancer-associated VTE (Table 2).
Which of the following medication is considered to manage VTE?
Options include: Anticoagulants, including injectables such as heparin or low molecular weight heparin, or tablets such as apixaban, dabigatran, rivaroxaban, edoxaban and warfarin (also called direct-acting oral anticoagulants or DOACs). These medications are used for a number of months.
What is VTE medication for?
It is used for prophylaxis and treatment of venous thrombosis, PE, and thromboembolic disorders.
Do cancer patients need anticoagulation?
Most patients with cancer-associated VTE are treated with anticoagulation unless there is active bleeding or a high risk of bleeding. While many are treated as inpatients, there is a growing population of patients that are suitable for outpatient therapy, which can affect agent selection.
Which DOAC to use in cancer patients?
Options for treating patients with cancer-associated thrombosis now include the direct oral anticoagulants (DOACs) edoxaban, rivaroxaban, and apixaban, in addition to low-molecular-weight heparins (LMWHs).
What is VTE prophylaxis?
Venous thromboembolism (VTE) prophylaxis consists of pharmacologic and nonpharmacologic measures to diminish the risk of deep vein thrombosis (DVT) and pulmonary embolism (PE).
How much more likely is venous thromboembolism in patients with malignancy than without malign
Patients with malignancy have four to seven times greater risk of venous thromboembolism (VTE) than seen in patients without known malignancy 1-4 and use of chemotherapy increases risk by 6.5-fold. 4
What is the most recent study to examine the use of DOACs for the treatment of cancer associated thrombos
The CARAVAGGIO trial is the most recent study to examine the use of DOACs for the treatment of cancer associated thrombosis. This larger, open label trial randomized 1170 cancer patients to receive apixaban (10mg twice daily for 7 days then 5mg twice daily) or dalteparin (200 IU/kg daily for 1 month followed by 150 IU/kg daily) for 6 months. As with other studies of DOACs, patients with basal-cell or squamous-cell skin cancers and ECOG status worse than two were excluded. Notable differences were the exclusion of patients with primary brain tumors, known intracerebral metastases, and acute leukemia. Approximately 68% of patients in each arm had recurrent locally advanced or metastatic disease and 60% in each arm were receiving concurrent cancer treatment. 20
How long is the HOKUSAI VTE trial?
The HOKUSAI VTE Cancer trial is an open-label, non-inferiority trial that randomized 1050 active cancer patients with acute VTE to either treatment with edoxaban or dalteparin for 6 to 12 months. 15 Basal and squamous-cell skin cancers as well as patients with Eastern Cooperative Oncology Group (ECOG) performance category worse than two were excluded. Overall, approximately 90% of patients had a solid tumor malignancy. Metastatic disease was found in 60% and 57% of patients in the dalteparin arm and edoxaban arm, respectively. Approximately 70% in each arm had received cancer treatment in the four weeks prior to their enrollment.
Why does rivaroxaban cause bleeding?
The authors suggest two possible reasons for the increased gastrointestinal bleeding: 1) increased antithrombotic effect of rivaroxaban and 2) local and systemic effects of rivaroxaban on the GI system.
Is death from any cause and event free survival significantly different between apixaban and daltepar
Death from any cause and event free survival were not significantly different between apixaban and dalteparin arms. The two most prevalent cancers in both arms of the HOKUSAI-VTE Cancer, SELECT-D and CARAVAGGIO trials were colorectal and lung. 15,18.
Is LMWH preferred for GI cancer?
Among those with GI/GU cancer- associated thrombosis, LMWH is preferred. VKA can be considered if patients are not candidates for LMWH or DOAC (e.g. cost), particularly for those with stable disease or in those in remission.
Is Apixaban a VTE?
Apixaban is non-inferior to dalteparin with respect to recurrent VTE and had similar rates of major bleeding. Like the other studies of rivaroxaban and edoxaban, there is increased risk of both major bleeding and CRNMB, particularly in those with GI and GU cancers.
How long does it take to treat a VTE?
Treatment of established cancer-associated VTE within 6 months consists of initial treatment (first 5–10 days) and early maintenance (up to 6 months) in the International Initiative on Thrombosis and Cancer (ITAC) guidelines [ 2 ], whereas of initial treatment (fir st 5–10 days) and long-term treatment (up to 6 months) in the American Society of Clinical Oncology (ASCO) guidelines [ 5 ]. Initial treatment of cancer-associated VTE is often defined as acute treatment especially the first 5 to 10 days of anticoagulant treatment [ 1, 2, 5, 12 ]. In the 2018 Cochrane database of systematic reviews with respect to the initial treatment of cancer-associated VTE, LMWH was possibly superior to adjusted-dose UFH [ 12 ].
What is a VTE?
Cancer-associ ated venous thromboembolism (VTE) is a common and life-threatening condition in adult patients (≥18 years) with cancer [ 1 ]. Patients with cancer are four to seven times more likely to develop VTE than patients without cancer [ 2 ]. The factors that are responsible for the increase of cancer-associated VTE incidence basically include ...
What anticoagulant is used for cancer?
To date, the pharmacological anticoagulant agents most frequently used for cancer-associated VTE are LMWH and DOACs. In a real-world analysis, from September 2018 to January 2020, LMWH was the most common initial anticoagulation treatment for VTE in patients with cancer. Nevertheless, DOACs had a lower risk of recurrent venous thromboembolism compared with LMWH or warfarin [ 7 ]. In a retrospective cohort study, LMWH and UFH were the most common initial treatments (35.2 and 27.4%, respectively) of cancer-associated VTE, followed by DOACs (9.6%). Most of patients (71.4%) who received DOACs sticked to the post-discharge DOACs medication, whereas only 24.1, 43.5, and 0.1% of patients receiving LMWH, warfarin, and UFH remained on the same anticoagulant after discharge, respectively. DOACs were the most common initial post-discharge outpatient option. Persistence and adherence in outpatients appeared higher in patients using DOACs or warfarin versus LMWH or UFH [ 8 ]. In another retrospective cohort study, from 2000 through 2003, warfarin ± injectable was used in approximately 90% of cases. After 2003, there was a steady decline in warfarin use (90% in 2003 to 25% in 2017) corresponding with an increase in LMWH use (11% in 2003 to 55% in 2017). The regimen of DOACs ± injectable has rapidly increased from < 1% in 2014 to 20% in 2017 [ 9 ]. In two recent meta-analyses, recurrent VTE incidence was significantly decreased with DOACs compared to LMWH [ 10, 11 ], with comparable [ 10] or increased [ 11] bleeding risks. VTE recurrence was also decreased with DOACs compared to VKA, with comparable [ 10] or decreased [ 11] bleeding risks. LMWH was associated with significantly reduced VTE recurrence compared with VKA [ 11 ].
How long does it take to treat venous thromboembolism?
Treatment of established VTE is often complex in patients with cancer. Treatment of cancer-associated VTE basically comprises initial treatment, long-term treatment, treatment within 6 months, treatment beyond 6 months, treatment of recurrent VTE, and treatment in special situations. Decision of antithrombotic therapy, selection of anticoagulants, duration of anticoagulation, decision of adjuvant therapy, and adjustment of regimen in special situations are the major problems in the treatment of cancer-associated VTE. Therapeutic anticoagulation is the key of the key in the treatment of cancer-associated VTE. In addition to the efficacy and safety of low-molecular-weight heparin (LMWH) that has been fully demonstrated, direct oral anticoagulants (DOACs) are increasingly showing its advantages along with the accompanying concern in the treatment of cancer-associated VTE. The latest ASCO, ITAC and NCCN guidelines agree with each other on most aspects with respect to the treatment of cancer-associated VTE, whereas differ on a few issues. Encompassing recent randomized controlled trials, clinical trials, and meta-analyses, as well as the comparison of the latest authoritative guidelines including the NCCN, ASCO, and ITAC guidelines in this field, the objective of this review is to present current overview and recommendations for the treatment of cancer-associated VTE.
Does thrombocytopenia reduce the risk of VTE?
Thrombocytopenia does not reduce the risk of VTE. It is not uncommon for thrombocytopenic patients with cancer to have an indication for anticoagulant therapy. Since bleeding risk due to anticoagulation increase when platelets are less than 50 × 10 9 /L, management options may include no change, temporarily withholding anticoagulant treatment, reducing dosage, switching to other regimens, and platelet transfusion in this situation [ 30 ]. In a retrospective study, the conventional dose of dalteparin 200 units/kg once daily was adopted for patients with platelets more than 50 × 10 9 /L. For patients with thrombocytopenia (platelets of 25–50 × 10 9 /L) ( n = 75), the dosage of dalteparin was reduced to 100 units/kg once daily. For patients with platelets less than 25 × 10 9 /L ( n = 77), dalteparin was withheld unless platelets recovered to exceed the 25 × 10 9 /L threshold. During a two-year observation, new or recurrent VTE was documented in 2.6, 0, and 2.2% of patients with platelet counts of< 25, 25–50, and > 50 × 10 9 /L, respectively. ( p > 0.9 for all comparisons). Acute blood loss or major bleeding events were documented in 10.5, 12.5, and 15.6% of patients with platelet counts of< 25, 25–50, and > 50 × 10 9 /L, respectively ( p > 0.9 for all comparisons) [ 31 ]. In the RIETE study, 166 (1.1%) had platelets less than 50 × 10 9 /L (severe thrombocytopenia), 711 (4.6%) had platelets of 50–99 × 10 9 /L (mild thrombocytopenia) and 14,460 (94.3%) had platelets more than 100 × 10 9 /L (normal count). Most patients received LMWH at conventional dose for initial therapy, whereas 62% of those with severe thrombocytopenia received LMWH less than150 IU/kg/day, and 42% of them received LMWH less than 100 IU/kg/day. The mortality rate progressively decreased along with the increase of platelet counts (12, 9.4 and 3.3% at 10 days, 27, 18 and 9.4% at 30 days, respectively), whereas the major bleeding rates did not differ among three groups (1.2, 2.5 and 1.3% at 10 days, 2.4, 4.4 and 2.2% at 30 days, respectively) [ 32 ].
Can heparin cause recurrent VTE?
Poor adherence, temporary cessation, inadequate dosage, cancer progression, and heparin -induced thrombocytopenia (HIT) can lead to recurrent VTE in cancer patients [ 26 ]. A study investigated the management of recurrent VTE in 212 cancer patients with breakthrough VTE which was defined as the first objectively verified VTE event after the initiation of anticoagulant therapy. The anticoagulation regimen changes after the breakthrough VTE were: dose unchanged in 33%, dose increased in 31%, switched to another agent in 24%, and other management in 11%. After 3 months of follow-up, additional VTE recurrence was less common with LMWH than with VKA (HR, 0.28; 95% CI, 0.11–0.70) [ 27 ].
Is VTE increasing?
The incidence of cancer-associated VTE is still increasing worldwide [ 2 ]. Cancer-associated VTE is an important cause of morbidity for patients with cancer [ 5 ]. Patients with cancer may require critical care for the complication of their malignancy. Pulmonary embolism is one of the complications that can lead to the intensive care unit (ICU) ...
What is a VTE in cancer?
Venous thromboembolism (VTE), comprising deep vein thrombosis (DVT) and pulmonary embolism (PE), is a common complication in cancer patients. The risk of developing VTE in these patients is fourfold to sevenfold increased compared with noncancer patients with a reported incidence of up to 15% per year. 1, 2 Several cancer-associated risk factors for VTE have been identified, including patient-, treatment-, and tumor-related factors ( Table 1 ). At present, cancer patients frequently undergo imaging for tumor staging and evaluation of treatment response, which is further increasing the underlying risk of VTE detection. 3 When VTE is diagnosed, anticoagulant therapy is indicated in almost all cases. However, the management of VTE is challenging in this patient population. The risk of recurrent VTE despite anticoagulant therapy and bleeding complications is higher among cancer patients compared with those without cancer. 4 In this review, we will discuss 3 common cancer-associated VTE patient scenarios and critically assess the evidence and recent advances to guide treatment decisions ( Figure 1 ).
What is a VTE?
Venous thromboembolism (VTE), which includes deep vein thrombosis and pulmonary embolism, is a common complication of cancer and is associated with significant morbidity and mortality. Several cancer-related risk factors contribute to the development of VTE including cancer type and stage, chemotherapy, surgery, ...
What is stage IIIA distal esophageal carcinoma?
A 72-year-old woman is diagnosed with stage IIIA distal esophageal carcinoma and started on neoadjuvant radiation therapy and chemotherapy with carboplatin and paclitaxel. Two months later, a multidetector CT scan with IV contrast was performed for evaluation of treatment response. An incidental filling defect was detected in a segmental pulmonary artery of the right lower lobe. The patient reported no dyspnea, chest pain, or hemoptysis. She had an active lifestyle and denied exertional dyspnea. Recently, she experienced 2 episodes of hematemesis. Blood pressure was 142/98 mm Hg; pulse rate, 59 per minute; temperature, 36.8°C; oxygen saturation, 98%; and respiratory rate, 17 per minute. Should this patient with incidentally detected PE receive anticoagulant treatment?
What percentage of cancer patients have incidental PE?
Up to 50% of all PEs in cancer patients are incidentally detected, and the prevalence of incidental PE diagnosis has been reported to be between 1% and 15% in this patient population. 3 Incidental PEs are most often diagnosed on multidetector CT scans performed to assess cancer treatment response, disease staging, or routine follow-up imaging. Although PE diagnosis is unsuspected in these patients, approximately one-half of the patients report symptoms suggestive of PE or DVT. 29, 30 Given that the signs and symptoms of PE are not specific, they are often attributed to the cancer itself or its underlying treatment by both the clinician and the patient, not immediately leading to suspicion of PE.
Is VTE a complication?
VTE is a common complication that is associated with significant morbidity and mortality in cancer patients. Different manifestations require specific treatment approaches as outlined in this review. Although LMWHs have been the recommended treatment of years, recent trials showed that DOACs can also be used for the management of cancer-associated thrombosis. Edoxaban and rivaroxaban have been studied in the setting of cancer-associated thrombosis, and a randomized trial evaluating apixaban is ongoing ( clinicaltrials.gov NCT03045406).
Is LMWH a good anticoagulant?
As the bleeding risk with DOACs for the treatment of catheter-associated thrombosis needs further assessment, LMWH may be the preferred anticoagulant option. However, DOACs may be considered a reasonable alternative after discussion with patients.
Is rivaroxaban an alternative to LMWH?
Taken together, the DOACs, edoxaban and rivaroxaban, seem to be an acceptable alternative to LMWH for the treatment of VTE in cancer patients . However, several factors need to be considered when tailoring anticoagulation management in a patient with cancer-associated thrombosis.
Guideline Implementation Tools and Resources
This one-page snapshot provides a high-level summary of the guidelines on the prevention and treatment of VTE in patients with cancer. A snapshot of the full VTE guidelines is also available for download.
Teaching Slides
Help your colleagues diagnose, manage, and treat VTE with the following teaching slides designed for easy dissemination:
What is a VTE?
Cancer-associated venous thromboembolism (VTE) is a frequent, potentially life-threatening event that complicates cancer management. Anticoagulants are the cornerstone of therapy for the treatment and prevention of cancer-associated thrombosis (CAT); factor Xa–inhibiting direct oral anticoagulants (DOACs; apixaban, edoxaban, and rivaroxaban), ...
What are the benefits of parenteral anticoagulants?
CAT management benefits from the availability of parenteral anticoagulants, particularly for patients experiencing nausea and vomiting or impaired gastrointestinal absorption. Long-standing experience with LMWH use, and the flexible LMWH dose adjustments, allows for easier or more flexible management of thrombocytopenia and invasive interventions than with other anticoagulants, for example, VKAs. 19, 27, 28 Challenges with parenteral administration (eg, inconvenience and discomfort of daily injections), alongside the high cost of LMWHs, 27, 29 may be burdensome for patients needing long-term anticoagulation therapy; CAT treatment guidelines support anticoagulation therapy for at least 3 to 6 months for the prevention of recurrent VTE. 16 - 20, 27
What is CAT in cancer?
Cancer-associated thrombosis (CAT) is a frequently encountered, life-threatening event that complicates cancer management and decreases survival. 1, 2 Cancer and anticancer treatments are well-established risk factors for venous thromboembolism (VTE), and cancer increases the risk of VTE 4- to 7-fold versus patients without cancer. 3 CAT makes a significant contribution to the burden of VTE, accounting for approximately 20% of all cases. 4 Anticoagulants are the cornerstone for the primary prevention and treatment of VTE but may be underused for CAT because of complications in management specific to patients with cancer. 5
Is Hokusai VTE effective for CAT?
Together, Hokusai-VTE-Cancer and SELECT-D provide evidence that DOACs are effective for CAT treatment, although the higher risk of bleeding with DOACs than with LMWH suggests that careful risk assessment and patient selection are needed.