Role of the PAR4 Thrombin Receptor in Stabilizing Platelet-platelet Aggregates as Revealed by a Patient with Hermansky-Pudlak Syndrome

Lidija Covic; Christopher Singh; Hedy Smith; Athan Kuliopulos

doi:10.1055/s-0037-1613071

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2002; 87(04): 722-727
DOI: 10.1055/s-0037-1613071

Review Article

Schattauer GmbH

Role of the PAR4 Thrombin Receptor in Stabilizing Platelet-platelet Aggregates as Revealed by a Patient with Hermansky-Pudlak Syndrome

Autor*innen

Lidija Covic

¹Division of Hematology/Oncology, Molecular Cardiology Research Institute, New England Medical Center and Departments of Medicine and Biochemistry, Tufts University School of Medicine, Boston, Massachusetts, USA
Christopher Singh

¹Division of Hematology/Oncology, Molecular Cardiology Research Institute, New England Medical Center and Departments of Medicine and Biochemistry, Tufts University School of Medicine, Boston, Massachusetts, USA
Hedy Smith

¹Division of Hematology/Oncology, Molecular Cardiology Research Institute, New England Medical Center and Departments of Medicine and Biochemistry, Tufts University School of Medicine, Boston, Massachusetts, USA
Athan Kuliopulos

¹Division of Hematology/Oncology, Molecular Cardiology Research Institute, New England Medical Center and Departments of Medicine and Biochemistry, Tufts University School of Medicine, Boston, Massachusetts, USA

Abstract

Summary

Individuals with Hermansky-Pudlak Syndrome (HPS) lack platelet dense granules and have no ADP-autocrine response. Despite these platelet deficiencies, HPS patients exhibit a surprisingly mild bleeding phenotype. We hypothesize that activation of the PAR4 thrombin receptor compensates for the lack of an ADP-autocrine response by the P2Y12 ADP receptor in individuals with HPS. Here, we determine that PAR4 activation by thrombin occurs well after ADP release from dense granules in normal individuals. However, the signal from PAR4 stabilizes platelet-platelet aggregate formation in the absence of P2Y₁₂ activation by ADP. Thus, the strong signal emanating from PAR4 during platelet aggregation would provide an explanation for the mild bleeding diathesis of HPS.

Keywords

Hermansky-Pudlak Syndrome (HPS) - PAR4 - PAR1 - P2Y12

Volltext

Referenzen

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