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Congenital and acquired disorders of platelet function

INTRODUCTION

Disorders of platelet function include several rare congenital disorders [1], as well as a myriad of common acquired conditions (eg, aspirin use, effects of other drugs, liver disease, uremia). The consultant Hematologist is often asked to evaluate patients with a bleeding disorder with clinical characteristics suggesting the presence of a qualitative and/or quantitative platelet disorder (eg, mucocutaneous bleeding and petechiae) (table 1).

This review will briefly summarize normal platelet function as well as available tests of platelet function. The major emphasis will be on the etiology, clinical evaluation, and available therapeutic options in patients with disorders of platelet function. General approaches to the patient with thrombocytopenia, thrombocytosis, or a bleeding disorder are discussed separately. (See "Approach to the adult with unexplained thrombocytopenia" and "Approach to the patient with thrombocytosis" and "Approach to the adult patient with a bleeding diathesis" and "Preoperative assessment of hemostasis".)

NORMAL PLATELET FUNCTION

A review of normal platelet function is required in order to understand functional platelet disorders, especially with the increasing number of therapeutic agents available that specifically target various stages of platelet function. There are four sequential steps that describe this function (figure 1). (See "Overview of hemostasis", section on 'Formation of the platelet plug' and "Overview of hemostasis", section on 'Clotting cascade and propagation of the clot' and "Platelet biology".)

Platelet adherence — Platelet-mediated hemostasis is initiated by exposure of the vascular subendothelium following injury to the endothelial surface. Circulating platelets are recruited to the site of injury and bind to exposed components of the subendothelium, including collagen, fibronectin, von Willebrand factor (VWF), fibrinogen, and thrombospondin via glycoprotein (GP) receptors on the platelet surface including GPIb/IX, GPIa/IIa, and integrin αIIbβ3 (integrin alphaIIbbeta3; previously known as GPIIb/IIIa) (figure 2) [2-4].

Platelet activation — Receptor-ligand binding leads to platelet activation, mediated through calcium-dependent cytoskeletal changes in the platelet. This outside-in signaling is followed by the release of substances from two sources. (See "Megakaryocyte biology and the production of platelets", section on 'Specific platelet granules'.)

                                         

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Literature review current through: Jul 2014. | This topic last updated: Aug 6, 2014.
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