Inherited Defects in Platelet Signaling Mechanisms

Gauthami Jalagadugula; Liansheng Sun; A. Koneti Rao

doi:10.1055/s-2004-835673

Seminars in Thrombosis and Hemostasis, Table of Contents

Semin Thromb Hemost 2004; 30(5): 525-535
DOI: 10.1055/s-2004-835673

Inherited Defects in Platelet Signaling Mechanisms

A. Koneti Rao¹ ^, ² , Gauthami Jalagadugula² , Liansheng Sun²

¹Professor of Medicine, and the Sol Sherry Thrombosis Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania
²Department of Medicine, and the Sol Sherry Thrombosis Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania

Abstract

In the majority of patients with an inherited abnormality in platelet function and a bleeding diathesis, the underlying platelet molecular mechanisms are unknown. The usually considered entities, such as thrombasthenia, the Bernard-Soulier syndrome, and storage pool deficiency, occur in a small proportion of patients. A substantial number of patients present with decreased aggregation and secretion of dense granule contents upon activation, and are lumped in the category of primary secretion defects or platelet activation defects. Evidence is now available that defects in platelet signaling mechanisms may be the basis for the platelet dysfunction in some of these patients. This evidence is presented here. If the key components in signal transduction are the surface receptors, the G-proteins, and the effectors, evidence now exists for specific human platelet abnormalities at each of these levels. There is a pressing need for a concerted effort to delineate the molecular mechanisms in the large group of patients with impaired platelet function who represent an untapped reservoir of new information into normal platelet function.

KEYWORDS

Platelet signal transduction - platelet function disorders - phospholipase C-β₂ - primary secretion defects - signal transduction defects

Full Text

References

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A. Koneti RaoM.D.

Division of Hematology and Thromboembolic Diseases, Temple University Health Sciences Center, Room 300 OMS

3400 N. Broad Street

Philadelphia, PA 19140

Email: koneti@temple.edu