Work

Antiplatelet-anticoagulant, APAC, a mimic of endogenous heparin, is an antithrombotic with von Willebrand factor-mediated characteristics

Year: 2025

Type: article

Abstract: BACKGROUND: We have conjugated selected number of unfractionated heparin (UFH) chains to human albumin core to mimic mast-cell heparin proteoglycans (HEP-PG). Indeed, APAC, dual antiplatelet and anticoagulant, as HEP-PG, has inhibited collagen- (CIPA) and thrombin-induced platelet aggregation, being simultaneously an anticoagulant. In several animal models of arterial thrombosis, APAC has provided vascular-injury-associated local antithrombotic properties mediated by von Willebrand factor (VWF). AIMS: We compared the structure-function effects of APAC with those of UFH in vitro, and when supplemented in blood studied platelet and VWF-dependency and anticoagulation. METHODS: We assessed the total thrombosis formation analysis system (T-TAS) and coagulation (rotational thromboelastometry, ROTEM) in blood, and thrombin generation and aggregation in platelet-rich plasma. We studied aggregation responses of APAC to collagen, ristocetin, ADP, and potential synergism with cangrelor, P2Y12 receptor antagonist. Finally, heparin-neutralizing role of platelet factor 4 (PF4) on antiplatelet and anticoagulant functions of APAC was investigated. RESULTS: APAC concentration-dependently exceeded the anticoagulant and antithrombotic action of UFH in ROTEM, and platelet thrombus formation under arterial blood flow over collagen/tissue factor. APAC uniquely inhibited CIPA. While ADP- and ristocetin-induced aggregation were unaffected by APAC, we detected synergism with cangrelor for CIPA. Disruption of the tertiary structure of APAC reverted its mode of action to anticoagulation only, alike UFH. PF4 neutralized antithrombotic actions of APAC. CONCLUSION: The structure-function of APAC conveys dual and unique antiplatelet and anticoagulant actions in flowing blood over collagen and beyond. Our studies confirmed the inhibitory role of APAC on VWF functions and fibrin formation.

Source: Thrombosis Research

DOI: 10.1016/j.thromres.2025.109318

Authors: Annukka Jouppila, Ilja Nevola, Marja Lemponen, Tomi Mattila, Riitta Lassila

Institutions: University of Helsinki, Helsinki University Hospital, Hospital District of Helsinki and Uusimaa

Language: English

Topic: Platelet Disorders and Treatments

Subfield: Hematology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $4,080