R. Lassila1-2, A. Jouppila3

1Comprehensive Cancer Center, Dept of Hematology, Coagulation Disorders Unit, Faculty of Medicine, Research Program in Oncology; 2Aplagon Ltd and 3Helsinki University Hospital Clinical Research Institute, Helsinki, Finland

INTRODUCTION

Mast cell heparin proteoglycans (HEP-PG) inhibit collagen- and von Willebrand factor (VWF)-mediated platelet thrombosis maintaining platelet adhesion1-4. APAC, platelet and fibrin inhibiting HEP-PG mimic1,5-7, is developed for antithrombotic management of vascular interventions.

Previous work shows that APAC

  • inhibits arterial thrombosis (Folts and AV-shunt model) and reduces fibrin formation in baboons (A and B)
  • reduces ischemic reperfusion injury in acute kidney injury model in rats (C)
  • decreasess platelet and fibrin deposition and procoagulant activity under VWF-dependent high shear rate conditions (D) in human blood in vitro

AIMS

to assess the role of APAC in

  • platelet aggregation in human blood and PRP
  • global blood coagulation (ROTEM)
  • targeting to injured porcine vascular sites
  • collagen-induced thrombosis in mouse

CONCLUSIONS

APAC unlike UFH

  • inhibits collagen- and ristocetin-induced platelet aggregation both in blood and PRP
  • is a broader anticoagulant
  • targets injured vascular sites: co-localizes with VWF and laminin – not the intact endothelium
  • reduces collagen-dependent platelet thrombus formation in mouse – without bleeds
  • in hemophilia with cardiovascular complications of thrombosis APAC may offer a safe local alternative for the current antithrombotics

RESULTS