Semin Thromb Hemost 2014; 40(08): 837-844
DOI: 10.1055/s-0034-1395157
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Mast Cell–Derived Heparin Proteoglycans As a Model for a Local Antithrombotic

Riitta Lassila
1  Aplagon Ltd, Helsinki, Finland
2  Coagulation Disorders Unit, Hematology and Cancer Center, Helsinki University Central Hospital, Helsinki, Finland
3  Medical faculty, University of Helsinki, Helsinki, Finland
,
Annukka Jouppila
4  Coagulation Disorders Unit, Helsinki University Central Hospital Research Institute, Helsinki, Finland
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Publikationsverlauf

Publikationsdatum:
13. November 2014 (online)

Abstract

Mast cell–derived heparin proteoglycans (HEP-PG) reside in vascular tissue and serve as a local antithrombotic. Heparin, as used clinically, is isolated from its protein backbone from porcine and bovine gut mucosa. The isolated heparin is an anticoagulant; however, when bound to a protein carrier the heparin conjugates will become antiplatelet agents by inhibiting collagen-induced platelet aggregation and procoagulant activity, as distinct from soluble heparin. HEP-PG, whether soluble or immobilized to a surface, inhibit platelet deposition on the collagen surface in flowing blood. Mimics of HEP-PG, can be tailored to molecules carrying both antiplatelet and anticoagulant (APAC) properties. These molecules can target the vascular injury site and take residence there. Inhibition of thrombus growth using these APACs under these conditions has been demonstrated in several animal models. Although efficacious for antiplatelet and anticoagulant effects, the bleeding time is shorter with APACs than with unfractionated heparin, suggestive of beneficial efficacy/safety ratio. These strategies may be utilized in drug development, where many vascular injury-related problems can be tackled locally.