Naveen Manchanda, MD
Long assumed to be inert carriers of coagulation proteins, platelets possess great functional complexity and maintain exquisite control. Platelets were named as derivates of RBCs. The observation William Osler made that “there was never a sign of blushing among platelets” (Robb-Smith, Brit J Haematology 1967) led to the conclusion that this was not true. From that rudimentary understanding of platelets to the current understanding of this complex cell has been an eventful journey. Capping this journey have been attempts to correct platelet disorders with gene transduction; success with using TPO-receptor agonist peptides in immune thrombocytopenia has been another scintillating advance.
There are education sessions on the clinical aspects of platelet functions, such as “Platelet Disorders” taking place at 9:30 a.m. today and tomorrow afternoon at 4:00 p.m. in Hall F3/F4. We saw how the diminutive denizens in our bloodstream could vanish, diminish, or be ineffectual. Dr. Adam Cuker will discuss advances in the treatment of idiopathic thrombocytopenic purpura (ITP) and shared his results of recently published trials of newer agents approved for this indication. Dr. Keith McCrae will address issues relating to thrombocytopenia in the pregnant patient. Meanwhile, platelets may be present but have aberrant function. Increasing numbers of drugs as well as intrinsic causes of platelet dysfunction are being recognized. Dr. Lawrence Brass will provide an extensive review of platelet function disorders and present some newly recognized functions of this once-thought-to-be-non-descript carrier of coagulation proteins.
The field of platelet biology equally has some intriguing presentations at this year’s annual meeting.
Bernard–Soulier syndrome (BSS) researchers from the Blood Research Institute in Milwaukee, WI, and the University of Arkansas for Medical Services, Little Rock, AR, will be presenting fascinating data on the rescue of BSS phenotype in a mouse model by lentivirus-mediated gene transfer of GPIbα during an oral session Monday, December 6, at 2:45 p.m. (abstract #552). This gene transfer was able to rescue the BSS phenotype in appropriately bred mice, notably with sustained expression of the integrin for several months. Moreover, these transduced hematopoietic stem cells could be used to rescue other mice afflicted by BSS, again attesting to the sustained expression of this molecule. This study advances the scientific attributes of lentiviral-associated gene transduction, in this case targeting megakaryocytes and thus platelets. It also points to possible interventions in treatment of inherited platelet disorders.
One often wonders … how do platelets die? During the same oral session as mentioned above, we will learn from Australian researchers that platelets are known to possess apoptotic pathways that are restrained to prolong their survival (abstract #550). Megakaryocytes also have apoptotic pathways, and these are supposed to be activated to produce platelets. Using transgenic mice deleted for certain pro-apoptotic genes, these researchers showed that megakaryocytes from these mice displayed adequate platelet shedding. This goes against the grain of current thinking that it is the process of apoptosis that leads to platelet budding from megakaryocytes. In fact, they found the apoptosis pathway needed to be restrained to enable platelet budding. Similarly, they have shown that chemotherapy and other insults activate the classical apoptosis pathway in megakaryocytes, thus enabling these cells to behave conventionally to extrinsic deleterious stimuli.
Hopefully this meeting will offer further avenues to understand the basic biology of platelets and apply it to clinical settings. From RBC dust to full-fledged cells, platelets have come a long way to their current better understood form.
Dr. Manchanda indicated no relevant conflicts of interest.