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Updated: May 29, 2026
Ferric Chloride-induced Murine Thrombosis Models
Published on: September 5, 2016
Therapeutic Strategies Combining Antiplatelet With Anticoagulant Actions: Heparin Proteoglycan Mimetic APAC as a
Axelle Y Kern1,2, Annukka Jouppila1,2, Hanna Pitkänen3,4
1Research Program in Systems Oncology, Faculty of Medicine, University of Helsinki, Finland (A.Y.K., A.J., R.L.).
Insights
A novel dual antithrombotic agent, antiplatelet and anticoagulant (APAC), effectively inhibits clot formation and reduces vascular lesions without increasing bleeding risk. This promising therapy shows potential for diverse patient populations, including those with pediatric cardiac conditions and peripheral arterial disease.
Area of Science:
- Cardiovascular Medicine
- Pharmacology
- Biomaterials Science
Background:
- Current antithrombotic therapies (aspirin, P2Y12 inhibitors, anticoagulants) carry significant bleeding risks.
- Suboptimal pharmacodynamics and non-individualized treatments limit efficacy in high-risk cardiovascular patients.
- Pediatric cardiac conditions and severe thrombophilia present unique antithrombotic challenges.
Purpose of the Study:
- To address limitations of current antithrombotic strategies.
- To develop a safe and effective dual-acting antithrombotic agent.
- To investigate the efficacy of antiplatelet and anticoagulant (APAC) in preclinical and clinical settings.
Main Methods:
- Development of APAC, a heparin proteoglycan mimetic with dual antiplatelet and anticoagulant properties.
- Administration of APAC locally or intravenously targeting von Willebrand Factor (VWF) and thrombin.
- Evaluation in preclinical models assessing atherosclerotic/stenotic lesions, inflammation, ischemia-reperfusion injury, and bleeding propensity.
- Assessment of APAC safety in early clinical trials and ongoing Phase 2 studies.
Main Results:
- APAC effectively inhibits platelet-fibrin deposition under high shear flow conditions.
- Preclinical studies demonstrated reduction in vascular lesions, inflammation, and ischemia-reperfusion injury without increased bleeding.
- Early clinical trials confirmed the safety of APAC with systemic and local administration.
Conclusions:
- APAC represents a promising, safe, and translational dual antithrombotic agent.
- APAC has the potential to overcome limitations of current therapies across diverse patient groups.
- Ongoing clinical trials are evaluating APAC for peripheral arterial disease and arteriovenous fistula patency.
Abstract:
Current antithrombotic therapies (combining aspirin, purinergic P2Y12 inhibitors, and anticoagulants) target both platelet and coagulation pathways to reduce ischemic events in high-risk cardiovascular patients. Despite efficacy, these regimens are limited by increased bleeding risk, as evidenced by multiple clinical trials. Suboptimal pharmacodynamics and nonindividualized treatment approaches complicate the therapeutic success. Pediatric cardiac conditions and severe thrombophilia underlying arterial and immune thrombosis pose special challenges. The dual actions aim at addressing these gaps by especially attenuating arterial platelet-rich thrombi and safety concerns. We highlight the need for improved antithrombotic strategies across diverse patient populations. To potentially overcome the limitations, we present antiplatelet and anticoagulant (APAC), a heparin proteoglycan mimetic integrating APAC effects. APAC, administered locally or intravenously, targets VWF (von Willebrand Factor) and thrombin, effectively inhibiting platelet-fibrin deposition, under high shear rate flow conditions over surfaces of collagen and TF (tissue factor). Preclinical models show that APAC reduces atherosclerotic and stenotic lesions, inflammation, and ischemia-reperfusion injury without bleeding propensity. These findings position APAC as a promising candidate for safe, translational dual antithrombotic. Early clinical trials demonstrated the safety of APAC under both systemic and local administration. A phase 2 clinical study in peripheral arterial disease is underway, and another is planned for arteriovenous fistula patency for end-stage renal patients.
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