Key result
SCE5-TAP, a platelet-targeted dual pathway antithrombotic, significantly inhibited venous thrombosis by 43.24% in mice without increasing bleeding risk compared to conventional anticoagulants.
Why the study?
Does SCE5-TAP inhibit thrombosis without compromising hemostasis in murine models of carotid artery and inferior vena cava thrombosis?
Does SCE5-TAP inhibit thrombosis without compromising hemostasis in murine models of carotid artery and inferior vena cava thrombosis?
p-value: p=<0.001
A novel platelet-targeted dual pathway antithrombotic (SCE5-TAP) effectively inhibits thrombosis in preclinical models without increasing bleeding risk, offering a potential strategy for safer antithrombotic therapy.
May reduce bleeding in dual pathway therapy; leaves open clinical translation.
Despite advances in antithrombotic therapy, the risk of recurrent coronary/cerebrovascular ischemia or venous thromboembolism remains high. Dual pathway antithrombotic blockade, using both antiplatelet and anticoagulant therapy, offers the promise of improved thrombotic protection; however, widespread adoption remains tempered by substantial risk of major bleeding. Here, we report a dual pathway therapeutic capable of site-specific targeting to activated platelets and therapeutic enrichment at the site of thrombus growth to allow reduced dosing without compromised antithrombotic efficacy. We engineered a recombinant fusion protein, SCE5-TAP, which consists of a single-chain antibody (SCE5) that targets and blocks the activated GPIIb/IIIa complex, and tick anticoagulant peptide (TAP), a potent direct inhibitor of activated factor X (FXa). SCE5-TAP demonstrated selective platelet targeting and inhibition of thrombosis in murine models of both carotid artery and inferior vena cava thrombosis, without a significant impact on hemostasis. Selective targeting to activated platelets provides an attractive strategy to achieve high antithrombotic efficacy with reduced risk of bleeding complications.
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Hanjaya‐Putra et al. (2018) studied Thrombosis. SCE5-TAP vs. Saline, MUT-TAP, enoxaparin, eptifibatide, rivaroxaban was evaluated on Thrombus inhibition in electrolytic inferior vena cava model (p=<0.001). SCE5-TAP, a platelet-targeted dual pathway antithrombotic, significantly inhibited venous thrombosis by 43.24% in mice without increasing bleeding risk compared to conventional anticoagulants.
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