Autosomal dominant thrombocytopenias with reduced expression of glycoprotein Ia

Patrizia Noris; Gianni F. Guidetti; Valeria Conti; Iride F. Ceresa; Michele Di Pumpo; Alessandro Pecci; Mauro Torti; Anna Savoia; Carlo L. Balduini

doi:10.1160/TH05-06-0421

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2006; 95(03): 483-489
DOI: 10.1160/TH05-06-0421

Platelets and Blood Cells

Schattauer GmbH

Autosomal dominant thrombocytopenias with reduced expression of glycoprotein Ia

Patrizia Noris

¹Department of Internal Medicine, University of Pavia – IRCCS Policlinico San Matteo, Pavia, Italy

,

Gianni F. Guidetti

²Department of Biochemistry, University of Pavia, Italy

,

Valeria Conti

³Telethon Institute of Genetics and Medicine (TIGEM), Naples, Italy

,

Iride F. Ceresa

¹Department of Internal Medicine, University of Pavia – IRCCS Policlinico San Matteo, Pavia, Italy

,

Michele Di Pumpo

¹Department of Internal Medicine, University of Pavia – IRCCS Policlinico San Matteo, Pavia, Italy

,

Alessandro Pecci

¹Department of Internal Medicine, University of Pavia – IRCCS Policlinico San Matteo, Pavia, Italy

,

Mauro Torti

²Department of Biochemistry, University of Pavia, Italy

,

Anna Savoia

³Telethon Institute of Genetics and Medicine (TIGEM), Naples, Italy

,

Carlo L. Balduini

¹Department of Internal Medicine, University of Pavia – IRCCS Policlinico San Matteo, Pavia, Italy

› Author Affiliations

Abstract

Summary

We have recently studieda case series of 46 unrelated patients with inherited thrombocytopenias and identified 18 cases that did not fit any known platelet disorder. In two unrelated families, a mild thrombocytopenia with normal platelet size was transmitted in an autosomal dominant fashion. Bleeding time was prolonged in 5 investigated patients. In all of them, flow cytometry and SDS-PAGE of platelet glycoproteins (GP) showed a reduced content of GPIa, a subunit of the GPIa-IIa complex (also known as integrin α2β1) that is a major collagen receptor on platelets.All other membrane GPs were within the normal range. GPIa deficiency was associated with severely reduced in vitro platelet adhesion to molecules known to interact selectively with GPIa. In vitro platelet aggregation was normal in all subjects, except for a suboptimal platelet response to fibrillar collagen in two patients.A mild defect of α-granules was observed in all affected subjects. No mutation was identified in the genes encoding for GPIa or GPIIa. Since no other similar cases have been reported in the literature, we suggest that an autosomal dominant thrombocytopenia associated with GPIa deficiency and α-granule defect represents a new form of inherited thrombocytopenia.

Keywords

Inherited thrombocytopenia - glycoprotein Ia - integrin α2β₁ - collagen receptor

Full Text

References

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