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An In vitro System to Gauge the Thrombolytic Efficacy of Histotripsy and a Lytic Drug
Published on: June 4, 2021
Novel antithrombotic strategies for treatment of venous thromboembolism
Jeffrey I Weitz1, Noel C Chan1
1Thrombosis and Atherosclerosis Research Institute, Hamilton, ON, Canada; and Department of Medicine, McMaster University, Hamilton, ON, Canada.
Insights
New anticoagulants targeting Factor XII and XI are needed to improve venous thromboembolism (VTE) treatment. Novel therapies aim to enhance fibrinolysis and reduce inflammation, offering safer options beyond current anticoagulation.
Area of Science:
- Hematology
- Vascular Medicine
- Pharmacology
Background:
- Venous thromboembolism (VTE), encompassing deep vein thrombosis (DVT) and pulmonary embolism (PE), is a leading cause of vascular mortality.
- Current anticoagulation therapies, while effective, carry significant bleeding risks, especially in cancer patients, and do not fully prevent long-term complications like post-thrombotic syndrome and chronic thromboembolic pulmonary hypertension.
Purpose of the Study:
- To highlight the need for safer anticoagulants for VTE treatment.
- To explore Factor XII and Factor XI as novel targets for anticoagulant development.
- To review emerging therapies aimed at enhancing endogenous fibrinolysis and reducing inflammation in VTE management.
Main Methods:
- Review of existing literature on VTE, current anticoagulation, and novel therapeutic targets.
- Analysis of the rationale and preclinical/clinical data for Factor XII and XI inhibitors.
- Examination of strategies targeting thrombin activatable fibrinolysis inhibitor and leukocyte-vessel wall interactions.
Main Results:
- Factor XII and XI inhibition presents a promising strategy for developing safer anticoagulants with potentially reduced bleeding risks.
- Therapies to enhance fibrinolysis in PE and reduce inflammation in DVT show potential for mitigating VTE-related complications.
- Ongoing research is evaluating the efficacy and safety of these novel antithrombotic agents.
Conclusions:
- Safer anticoagulants are crucial for effective VTE management, particularly given the limitations and risks of current treatments.
- Targeting Factor XII and XI, alongside strategies to modulate fibrinolysis and inflammation, represents the future of VTE therapy.
- These novel approaches offer significant opportunities to improve patient outcomes and reduce the burden of VTE and its sequelae.
Abstract:
Venous thromboembolism (VTE), which includes deep vein thrombosis (DVT) and pulmonary embolism (PE), is the third most common cause of vascular death after heart attack and stroke. Anticoagulation therapy is the cornerstone of VTE treatment. Despite such therapy, up to 50% of patients with DVT develop postthrombotic syndrome, and up to 4% of patients with PE develop chronic thromboembolic pulmonary hypertension. Therefore, better therapies are needed. Although direct oral anticoagulants are more convenient and safer than warfarin for VTE treatment, bleeding remains the major side effect, particularly in cancer patients. Factor XII and factor XI have emerged as targets for new anticoagulants that may be safer. To reduce the complications of VTE, attenuation of thrombin activatable fibrinolysis inhibitor activity is under investigation in PE patients to enhance endogenous fibrinolysis, whereas blockade of leukocyte interaction with the vessel wall is being studied to reduce the inflammation that contributes to postthrombotic syndrome in DVT patients. Focusing on these novel antithrombotic strategies, this article explains why safer anticoagulants are needed, provides the rationale for factor XII and XI as targets for such agents, reviews the data on the factor XII- and factor XI-directed anticoagulants under development, describes novel therapies to enhance fibrinolysis and decrease inflammation in PE and DVT patients, respectively, and offers insights into the opportunities for these novel VTE therapies.
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