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Venous thromboembolism (VTE) is a common complication among patients suffering from malignancies, leading to increased mortality. Novel randomized trials have added valuable information regarding cancer-associated thrombosis (CAT) management using direct oral anticoagulants (DOACs).
Venous thromboembolism (VTE) is a common complication among patients suffering from malignancies, while the risk of VTE varies during the progression of the disease . Different mechanisms and risk factors have been related to cancer-associated thrombosis (CAT) and could be differentiated into patient, tumor, and treatment related . Regarding patients suffering from CAT, the risk of fatal pulmonary embolism as well as bleeding is expected to be significantly higher compared to that among the general population . Thus, CAT patients represent a special group, concurrently presenting a high risk for life-threatening thrombotic and bleeding events. Chemotherapy may be an additional significant VTE-associated mortality risk factor . The estimated incidence of VTE in patients under chemotherapy is 9%, while the associated VTE mortality presents a 47-fold increase compared to that among the overall population .
In 2016, the revised American Community of Chest Physicians (ACCP) guidelines recommended the use of low molecular weight heparin (LMWH) over vitamin K antagonists (VKA) or direct oral anticoagulants (DOACs) in patients suffering from CAT . In recent years, novel studies and randomized controlled trials (RCTs) have added further information regarding CAT management, and newer data have been included in the more recent recommendations.
2. Current Recommendations on CAT Management
|Societies’ recommendations||International Society of Thrombosis and Hemostasis (ISTH) 2018||In Itiative on Thrombosis and Cancer (ITAC/CME) 2019||European Society of Cardiology (ESC) 2019||American Society of Clinical Oncology (ASCO) 2020||American Society of Hematology (ASH) 2021||European Society for Vascular Surgery (ESVS) 2021|
|Anticoagulant choice||Use of specific DOACS (edoxaban, rivaroxaban) and LMWHs are the preferred pharmaceutical choices
(Weak guidance) LMWHs are preferred in patients with high bleeding or DDI risk
|Initial phase (5–10 days): LMWH, rivaroxaban, or edoxaban following ≥5 days of parenteral anticoagulation (Grade 1B)
Long-term (<6 months): LMWH or DOACs (edoxaban, rivaroxaban) (Grade1A)
Extended therapy (>6 months): LMWH or DOACs (Grade 1A0
|In patients with PE and cancer, LMWH should be considered for the first 6 months over VKAs.
(Class IIa Level A)
Rivaroxaban and edoxaban should be considered as alternatives to LMWHs in patients without gastrointestinal cancer (Class IIa Level C and Class IIa Level B, respectively)
|Initial phase (5–10 days): LMWH, fondaparinux or rivaroxaban preferred (evidence quality: high; strength of recommendation: strong)
Long-term (<6 months): LMWH, edoxaban or rivaroxaban (VKAs are acceptable alternatives for long-term therapy if LMWH/DOACs not available) (Evidence quality: High; Strength of recommendation: strong)
Extended therapy (≥6 months): LMWH, edoxaban or rivaroxaban or VKAs (evidence quality: low; strength of recommendation: weak to moderate)
|DOACs (rivaroxaban, apixaban) as prophylaxis in ambulatory high thrombotic risk cancer patients under systemic therapy (moderate evidence)
Initial phase (<7 days): LMWHs or DOACs (apixaban, edoxaban, rivaroxaban) as alternative (very low evidence)
Long-term (3–6 months): DOACS over LMWH (Low evidence)
Extended therapy (>6 months): DOACS or LMWHs (very low evidence)
|LMWHs as standard of treatment in initial and principal phase (Class I Level A)
Extended therapy (>6 months): DOACs (Class I Level C)
DOACs as an alternative in patients without GI or genitourinary cancer for initial, principal, and extended treatment (Class IIa Level A)
|Societies’ recommendations||ISTH 2018||ITAC/CME 2019||ESC 2019||ASCO 2020||ASH 2021||ESVS 2021|
|Duration of therapy||NR||LMWHs or DOACs should be used for a least 6 months, while extension should rely on individualized evaluation (Grade 1A)||Extended anticoagulation (>6 months) should be considered for an indefinite period or until cancer is cured (Class IIa Level B)||Extended therapy may be considered in active cancer (evidence quality: low; strength of recommendation: weak to moderate)||Extended anticoagulation (>6 months) should be considered for an indefinite period in active cancer (low evidence)||Extended anticoagulation (>6 months) should be considered for an indefinite period in active cancer (in text)|
|Societies’ recommendations||ISTH 2018||ITAC/CME 2019||ESC 2019||ASCO 2020||ASH 2021||ESVS 2021|
|Aim & weighting the evidence||To outline expert experience and the biological rational that may affect clinical decision
The guidance statements are in accordance with the following premises:
1. Average patient with cancer and VTE
2. “we recommend” reflects a strong guidance with strong consensus among the panel
3. ”We suggest” reflects a weak guidance with moderate consensus among the panel
|To establish a global consensus for the treatment and prophylaxis of VTE in patients with cancer
The GRADE approach was used by an expert panel to conduct a systematic review of the current literature. The level of evidence was characterized as high (A), moderate (B), low (C), and very low (D), while the level of recommendation was strong (grade 1), weak (grade 2), and characterized as best clinical practice (guidance)
|To suggest optimal objectively validated management strategies for patients with suspected or confirmed PE.
Conclusions based on the available scientific evidence, using the European Society of Cardiology grading system (A, B, or C indicates the level of current evidence). Depending on the strength of recommendation, each one is categorized as Class I, IIa/IIb, and III.
|To provide updated recommendations about prophylaxis and treatment of VTE in patients with cancer
A systematic review of RCTs reporting on VTE prophylaxis and treatment using PubMed and CENTRAL databases, executed by an expert commit using the “signals” approach
|To support patients, clinicians, and others in decisions about treatment of VTE
The Grading of Recommendations Assessments, Development and Evaluation (GRADE) approach was used by an expert panel
|To assist clinicians in selecting the best management strategies to achieve optimal patient outcomes
Revision and summary of the relevant peer reviewed published literature. Conclusions based on the available scientific evidence, using the European Society of Cardiology grading system (A, B, or C indicates the level of current evidence). Depending on the strength of recommendation, each one is categorized as Class I, IIa/IIb, and III.
This entry is adapted from 10.3390/medicina57090960
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