[Anticoagulants: current topics]
1Department of Clinical Laboratory Science, Graduate School of Medical Science, Kanazawa University.
Abstract:
Despite the introduction of direct oral anticoagulants (DOAC), the need for more effective and safer antithrombotic strategies exists. Recently, the findings stating that the contact system is important for thrombus formation has identified factor XI as a potential target for new anticoagulants. Approximately 20-30% of patients who develop venous thromboembolism (VTE) also have cancer. To date, the drugs primarily used in the treatment of VTE are heparin in the acute phase and warfarin in the chronic phase. Recently, a large-scale international clinical trial, which examined the composite outcomes of VTE recurrence and major bleeding in cancer patients, found that edoxaban, a direct factor Xa inhibitor, is not inferior to low-molecular-weight heparin. The study also showed that DOACs have a promising potential to prove therapeutically effective in future studies. Anticoagulants are associated with a severe side effect, bleeding, which makes emergency neutralization an important concern. Four-factor prothrombin complex concentrate can be used to reverse the effect of warfarin and could also be effective as a neutralizing agent in patients having received DOACs. Moreover, more specific reversing agents include the approved human monoclonal antibody fragment idarucizumab for reversing the effects of dabigatran.
Insights
New anticoagulants targeting factor XI are needed for venous thromboembolism (VTE) in cancer patients. Direct oral anticoagulants like edoxaban show promise, with specific reversal agents available for bleeding emergencies.
Area of Science:
- Pharmacology and Thrombosis Research
- Oncology and Anticoagulation
Background:
- Current anticoagulants like heparin and warfarin have limitations, necessitating safer and more effective antithrombotic strategies.
- The contact system, particularly factor XI, is identified as a potential target for novel anticoagulant therapies.
- Venous thromboembolism (VTE) affects a significant portion of cancer patients, complicating their treatment.
Purpose of the Study:
- To evaluate the efficacy and safety of direct oral anticoagulants (DOACs) in cancer patients with VTE.
- To explore the potential of factor XI as a target for new anticoagulant development.
- To discuss the importance of emergency neutralization strategies for anticoagulants.
Main Methods:
- A large-scale international clinical trial assessed composite outcomes of VTE recurrence and major bleeding.
- Comparison of edoxaban (a direct factor Xa inhibitor) versus low-molecular-weight heparin in cancer patients.
- Review of existing and emerging anticoagulant reversal agents.
Main Results:
- Edoxaban demonstrated non-inferiority to low-molecular-weight heparin in preventing VTE recurrence and major bleeding in cancer patients.
- Direct oral anticoagulants (DOACs) show promising therapeutic potential in future studies.
- Four-factor prothrombin complex concentrate and idarucizumab are discussed as effective reversal agents.
Conclusions:
- Direct oral anticoagulants (DOACs) represent a viable therapeutic option for VTE in cancer patients.
- Targeting factor XI offers a promising avenue for developing safer anticoagulants.
- Availability of specific reversal agents enhances the safety profile of anticoagulant therapy.
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