Pathophysiology and therapeutic options in primary immune thrombocytopenia.

Abstract

The acronym ITP stands for primary immune thrombocytopenia (formerly idiopathic thrombocytopenic purpura), an acquired autoimmune disorder characterised by isolated thrombocytopenia in the absence of conditions known to cause thrombocytopenia, such as infections, other autoimmune disorders, drugs, etc1. Manifestations of ITP can be localised haemorrhaging in skin or mucous membranes that are usually of little to no clinical consequence (petechiae, purpura, ecchymoses, epistaxis); more rarely, ITP can be associated with severe bleeding events such as intracranial haemorrhage (ICH). However, most ITP patients are asymptomatic in the presence of platelet counts greater than 50x109/L2. ITP can be classified based on patient age (adult or childhood ITP), and duration of thrombocytopenia: newly diagnosed, up to 3 months from diagnosis; persistent, 3–12 months from the time of diagnosis; chronic, >12 months from the time of diagnosis1. The clinical features of ITP in adults are usually different from those seen in childhood. ITP in children usually has an abrupt (“acute”) onset, often occurring 1 to 2 weeks after a viral infection or 2 to 6 weeks after immunization with the measles, mumps and rubella (MMR) vaccine3,4, and recovers spontaneously in a few weeks regardless of treatment. In contrast, ITP in adults typically has an insidious onset, with no preceding viral or other illness, and has frequently a chronic course. Design of prospective, controlled clinical trials has been particularly difficult, since patients with the chronic disease needing treatment are less than 10% of all ITP patients5. Nevertheless, randomised trials with several new pharmacologic agents have recently changed this scenario. In this review we shall summarize the current understanding of the pathophysiology and mechanisms leading to thrombocytopenia and the evolving therapeutic modalities for chronic refractory ITP in adults.