Chronic Immune Thrombocytopenia

Introduction

Immune thrombocytopenia (ITP) is a bleeding disorder characterized by immune-mediated platelet destruction with resultant thrombocytopenia and mucocutaneous bleeding. Chronic ITP is defined by ITP persistence beyond 12 months, with spontaneous recovery occurring in less than 10% of adults. The estimated incidence of ITP is ∼100 cases per 1 million persons per year, with about half in adults. Approximately twice as many women are affected as men. Patients with chronic ITP often have problematic bleeding that requires ongoing therapy, and hemorrhagic deaths are not uncommon. Chronic ITP in adults is presented in this chapter. Newly diagnosed/childhood ITP is reviewed in Chapter 101 .

Pathophysiology

Chronic ITP is a heterogeneous disease that may be the common end-stage phenotype of numerous immunologic insults. The initiating event is a complex immunologic process, involving platelets, megakaryocytes, B cells, T cells, and other components of the immune system. A major feature of ITP is the Fc receptor–mediated clearance of IgG autoantibody–coated platelets by macrophages in the reticuloendothelial system. Platelet-associated IgG autoantibodies can be measured in about 50%–60% of patients with ITP and are usually reactive to platelet surface glycoproteins such as GPIIb/IIIa, GPIa/IIa, and GPIb/IX. However, approximately 40%–50% of patients do not have measurable antibodies, and therapies aimed at reducing autoantibody production and autoantibody-mediated platelet destruction are effective in only 50%–70% of patients.

T cells and their secretory factors are important for the stimulation of antibody-producing B-cell clones and may be important in the development of antiplatelet antibody production. Cytotoxic T cells from ITP patients can also destroy platelets with a high effector cell to target ratio. Platelet autoreactive T-cell clones have been identified in patients with chronic ITP, and genes involved in T cell–mediated cytotoxicity are upregulated in many ITP patients. Regulatory T cells that normally suppress autoreactive B-cell clones are defective in some patients with chronic ITP.

The pathophysiology of ITP also involves decreased or inadequate production of platelets. Thrombopoietin levels can be inappropriately low in patients with ITP. Additionally, antiplatelet antibodies and possibly antiplatelet T cells suppress production and maturation of bone marrow megakaryocytes.

Clinical Manifestations

The physical findings associated with chronic ITP are usually limited to those associated with thrombocytopenia and include petechiae, ecchymoses, and purpura. Mucocutaneous bleeding can be widespread and may include epistaxis, gingival bleeding, hematuria, and menorrhagia. Rarely, patients manifest severe bleeding, such as intracranial hemorrhage. The clinical evaluation of a patient with chronic ITP must also include a detailed past medical and family history, medication history, and review of systems.