Inherited defects in platelet signaling mechanisms.
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.
Rao
A Koneti
AK
Department of Medicine, Sol Sherry Thrombosis Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania, USA. koneti@temple.edu
Jalagadugula
Gauthami
G
Sun
Liansheng
L
D016718:Arachidonic Acid / Q000378:metabolism; D001606:Bernard-Soulier Syndrome / Q000097:blood; D001792:Blood Platelets / Q000166:cytology* / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism; D004789:Enzyme Activation; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000172:deficiency; D008954:Models, Biological; D054799:Phospholipase C beta; D010981:Platelet Storage Pool Deficiency / Q000097:blood; D011493:Protein Kinase C / Q000378:metabolism; D015398:Signal Transduction; D013915:Thrombasthenia / Q000097:blood; D013928:Thromboxane A2 / Q000378:metabolism; D013930:Thromboxane-A Synthase / Q000378:metabolism; D010738:Type C Phospholipases / Q000172:deficiency
D007527:Isoenzymes; D016718:Arachidonic Acid; D013928:Thromboxane A2; D011493:Protein Kinase C; D010738:Type C Phospholipases; D054799:Phospholipase C beta; D019204:GTP-Binding Proteins; D019205:GTP-Binding Protein alpha Subunits, Gs; D013930:Thromboxane-A Synthase