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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

Lidija Covic
1   Division 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
1   Division 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
1   Division 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
1   Division 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
› Author Affiliations
Further Information

Publication History

Received 31 October 2001

Accepted after revision 21 December 2001

Publication Date:
08 December 2017 (online)

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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
 

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