By Michael McDevitt, MD, PhD

2008-12-08

Several presentations were organized to present updates related to important aspects of platelet number and function, including a very interesting scientific committee session titled Platelet Life Cycle, which reviewed the scientific basis of megakaryocyte-to-platelet production this past Saturday and Sunday. The transcriptional regulation of thrombopoiesis was first reviewed by Dr. Alan Cantor. A number of key transcription factors that have been identified to play essential roles in megakaryocyte development were discussed. Mutations in the genes encoding several of these have been linked to human disorders of thrombopoiesis. Using proteomic approaches, Dr. Cantor’s group has identified several multi-protein complexes that are providing novel molecular insights into the control of megakaryocyte lineage determination, differentiation, and terminal maturation.

Dr. Elisabeth Cramer-Bordé and colleagues followed Dr. Cantor with a presentation that reviewed platelet birth. Platelet birth occurs when megakaryocytes (MKs) undergo compartmentalized cell death/apoptotic activity. Her talk reviewed mechanisms regulating platelet formation and release by human MKs. Unpublished impressive technical investigations demonstrated the positive effect of shear forces on proplatelet and platelet formation and release. A new familial cytochrome c mutation was described that sheds light on the importance of finely tuned apoptosis for triggering appropriate platelet release out of the bone marrow. This mutation leads to the premature release of platelets in the bone marrow, preventing their natural birth into the circulation, and thus clinical thrombocytopenia. The third presentation of the session reviewed platelet death. Human platelets exhibit a circulating lifespan of approximately 10 days. After five to 10 days in the circulation, platelets not consumed in hemostatic processes initiate a cell death program and clearance from the bloodstream. Dr. Emma Josefsson presented work that supports the idea of crosstalk between classical platelet signaling pathways, intrinsic apoptosis pathways, and the regulation of platelet biogenesis, function, and death, although much remains to be elucidated.

This past Saturday, an Education session devoted to chronic immune thrombocytopenia (CITP) focused on clinical aspects of thrombocytopenia. The association of Helicobacter pylori infections and CITP was reviewed by Dr. Roberto Stasi, of Ospedale Regina Apostolorum in Italy. Eradication of H. pylori infection has been variably associated with a platelet response in patients with ITP. Clinical features and proposed pathogenic mechanisms that might explain some of the epidemiological variance were discussed. Chronic infection with human immunodeficiency virus and hepatitis C are also well-recognized causes of CITP. Dr. Howard Liebman, from the University of Southern California, Los Angeles, provided a practical review of diagnosis and treatment of these unfortunately not uncommon conditions. In the final presentation of the session, Dr. Terry Gernsheimer, from the Puget Sound Blood Center in Seattle, reviewed ineffective thrombopoiesis and the exciting emerging roles of thrombopoietin receptor agonists in the management of CITP.

The current mainstay approach to patients with severe non-immune-based thrombocytopenia remains allogeneic platelet transfusions. A session jointly sponsored by ASH and AABB, Transfusion Medicine: New Strategies for the Use of Platelet Transfusion, was presented this past Saturday. New strategies for the optimal use of platelet transfusions were summarized by Dr. Blajchman from McMaster University. Colleagues Sherrill J. Slichter, MD, Nancy M. Heddle, MSc, and Michael Murphy, MD, presented background information and preliminary results of several large clinical trials set up to evaluate prophylactic versus therapeutic platelet transfusions, optimal transfusion triggers for prophylactic platelet transfusions, and the correct quantity of platelets to be transfused prophylactically per transfusion episode (TOPPS, PLADO, and SToP trials, respectively).

Platelets are prepared from platelet-rich plasma; this 50th anniversary meeting has turned out to be very platelet-rich indeed.

Dr. McDevitt indicated no relevant conflicts of interest.

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