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Essential Thrombocythaemia

Platelets – From Function to Dysfunction in Essential Thrombocythaemia Robert K Andrews,1

Michael C Berndt2 and Ismael Elalamy3

1. Associate Professor, Australian Centre for Blood Diseases, Monash University; 2. Director, Biomedical Diagnostic Institute, Dublin City University; 3. Professor, Haematology Department, Hôpital Tenon Paris University VI


Platelets are an important component of blood. The main biological role of platelets is to respond to vascular injury and promote thrombus formation to prevent bleeding. However, we now know that platelets also have additional functions in a variety of processes such as immunity, inflammation, coagulation, atherogenesis and tumour metastasis. Platelet disorders commonly lead to defects in haemostasis. Of particular interest is the myeloid proliferative disorder, essential thrombocythaemia (ET). In ET the increased number of platelets leads to an increased risk of blood clot formation and subsequent thrombohaemorrhagic complications. Here we provide a general review of platelet function and activation, as well as more detailed information on the dysfunction of platelets in patients with ET.

Keywords Haemostasis, megakaryocytes, platelets, platelet adhesion, platelet aggregation, platelet receptors

Disclosure: The authors have no conflicts of interest to declare. Acknowledgements: The authors directed writing assistance from Ewen Buckling, an employee of iMed Comms. Editorial assistance in the form of proofreading, copy editing and fact checking was also provided by iMed Comms. iMed Comms was funded by Shire Pharmaceuticals for support in writing and editing this manuscript. This article was conceived at a Shire-sponsored scientific advisory board, at which Michael C Berndt and Ismael Elalamy were attendees and were recompensed for their attendance. Although the sponsor was involved in the assessment of the potential need for such a review article and the factual checking of information, the ultimate interpretation was made by the independent authors, as was the content of this manuscript and the decision to submit it for publication in European Oncology & Haematology. Received: 1 February 2011 Accepted: 14 March 2011 Citation: European Oncology & Haematology, 2011;7(2):125–31 Correspondence: Ismael Elalamy, Service d’Hématologie Biologique, ER2-UPMC, Hôpital Tenon, 4 Rue de la Chine, 75790 Paris, France. E:

Support: The publication of this article was funded by Shire Pharmaceuticals. The views and opinions expressed are those of the authors and not necessarily those of Shire Pharmaceuticals.

Blood platelets could be easily overlooked as they appear inconsequential in blood smears in comparison with red cells and white cells. These small, discoid cells, 1–2µm across,1

are large in

number, with 100–450 billion per litre of healthy blood, and appear as a turbid suspension in platelet-rich plasma (PRP) when erythrocytes/ leukocytes are removed by low-speed centrifugation. By 2010, the functional importance of platelets had far surpassed their well-known role in haemostasis and thrombosis, and a recent article2


many new or suspected roles for platelets in development, as well as in vascular processes such as inflammation, immunity, coagulation, atherogenesis and tumour metastasis. But what are the properties of platelets in healthy individuals, how are the number and function of platelets regulated and how do perturbations due to injury, infection, drugs or acquired or inherited diseases impact platelet function? This article will discuss the biology of platelets and the implications of changes in the normal functioning of platelets with a particular focus on one of the myeloproliferative disorders (MPDs), essential thrombocythaemia (ET).

Platelet Production

Platelets are derived from the fragmentation of precursor megakaryocytes in the haematopoietic lineage. The mechanisms by which these nucleated cells form elongated structures that break down into individual platelets have been determined in great detail. During maturation over several days, megakaryocytes transform into


proplatelets (elongated branched tubular structures containing cytoplasm). New platelets form at the tips of the megakaryocyte protrusions as subcellular granules and organelles are delivered to the proplatelet from the megakaryocyte body (see Figure 1A).3


mechanism is important, because diseases or drug treatments, particularly chemotherapy, which impair platelet production result in a low platelet count (thrombocytopaenia), which can result in bleeding or deficiency in other platelet functions. A typical adult human might produce a hundred billion (1011) platelets every day, and 5,000–10,000 platelets per megakaryocyte. This can be mimicked in vitro, albeit on a far smaller scale, by treating cultured haematopoietic cells with growth factors like thrombopoietin, usually produced by the liver and kidneys.

Platelet Clearance

The balance between platelet production from megakaryocytes and clearance of platelets from the circulation controls the platelet count. There are several causes of platelet clearance.

• Anucleate platelets have a normal lifespan of seven to 10 days, and aged platelets are cleared from the circulation by phagocytosis in the spleen and/or by phagocytic Kupffer cells in the liver.

There is rapid immunological clearance caused by antiplatelet autoantibodies resulting in autoimmune diseases such as drug-induced autoimmune thrombocytopaenia or idiopathic thrombocytopaenia (ITP).


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