Platelet Physiology

July 12, 2003
14:00 to 18:00
Hall 9
The International Convention Center, Birmingham

Chairman:  A. Koneti Rao, USA
Co-chairs:  M. Berndt, Australia; M. Cattaneo, Italy; C. Cerletti, Italy; C. Hayward, Canada;
J. López, USA; A. Michelson, USA; P. Nurden, France; S. Watson, UK

The platelet subcommittee discussed three main themes at this meeting.  The first theme was in the area of application of expression profiling and proteomics to the study of platelets.  The second theme was on the molecular mechanisms in defective platelet production and congenital thrombocytopenias, and the third set of discussions focused on GPIIb-IIIa antagonists and their impact on activation of the integrin complex.  

I. Genomics, Proteomics: Methodology and Relevance.  

As a part of this session, Dr. Wadi Bahou summarized recent information on the application of expression profiling to human platelets.  Dr. Steve Watson summarized recent studies on the platelet proteome.  These presentations and the subsequent discussions focused on the methodology, their limitations when applied to platelets, and relevance of these techniques to the study of platelets. Both speakers emphasized the need for additional studies to define the optimal ways to apply these techniques to study platelets.

II. Molecular Mechanisms in Defective Platelet Production and Congenital Thrombocytopenias. (Working Group on Platelet Function Disorders)

This part of the session had five speakers.  The goal of these presentations was to summarize recent information on the molecular and genetic mechanisms in the areas of platelet production and congenital thrombocytopenias.  Dr. Ramesh Shivdasani presented new information obtained from the various knock-out models, including for NF-E2 and tubulin 1.  Dr. Andrew Leavitt presented studies on the regulation of GPIIb-IIIa function and the interactions with caspase-12 and transcription factor NF-E2.  Dr. A. Koneti Rao presented new evidence in human platelets on a mutation in transcription factor CBFA2 and its association with impaired activation of GPIIb-IIIa and platelet PKC-theta deficiency.  Dr. Carlo Balduini presented evidence supporting a unifying theme for MYH-9 gene mutations in congenital thrombocytopenias, encompassing the May Hegglin anomaly, the Fechtner syndrome, the Epstein syndrome and others.  Lastly, Dr. Jim Bussel described the current activity with regards to the development of  a Registry of Non-immune Thrombocytopenias. He invited members to participate in the Registry and described the information being collected along with the procedures.  The sub-committee endorsed this effort.

III.GPIIb-IIIa Antagonists and Activation of Integrin Complex:  Evidence and Clinical Relevance.  

Evidence from previous studies have suggested that GPIIb-IIIa antagonists may lead to conformational changes in the complex and to its activation. However, the biological and clinical significance is controversial.  Four speakers presented evidence and different aspects related to this theme.  Drs. Jose Lopez, A. Lawrence Frelinger, Paquita Nurden, and Stan Heptinstall presented their studies on this issue and there was a discussion regarding the data presented and their significance. It was recognized that additional studies were needed to define the clinical relevance of the observations presented.