Mechanisms of action of therapeutics in idiopathic thrombocytopenic purpura

Idiopathic thrombocytopenic purpura (ITP) is a common immune disorder caused by platelet-reactive autoantibodies. Antibody-coated platelets are cleared more rapidly from the circulation, often in the spleen, than they can be replaced by compensatory stimulation of platelet production in the bone marrow. In some patients, platelet production is depressed as well. ITP in adults does not generally remit spontaneously, and most patients require treatment to prevent bleeding at one time or another. Therapy with corticosteroids, danazol, intravenous immune globulin, anti-D antibody, and several other agents inhibits clearance of the antibody-coated platelets but is rarely curative. Most patients will sustain a hemostatic response after splenectomy, although relapses may occur at any time. Patients may be more responsive to these same modalities after splenectomy, but treatment with an immunosuppressant that inhibits T- and B-cell function and cooperation, including azathioprine, cyclophosphamide, cyclosporine, mycophenolate mofetil, or anti-CD20, may be required. Antiviral therapy is useful in patients with HIV or hepatitis C infection, but no consensus has been reached as to the efficacy of antibiotics to eradicate Helicobacter pylori. Promising results have been seen in several patients treated with a modified thrombopoietin. It may be possible to design therapeutics that exploit the apparent restricted immunoglobulin gene usage by antiplatelet antibodies, perhaps in the form of engineered anti-idiotypic antibodies or other compounds that specifically target autoantibody-producing B cells. Rationale therapy awaits a more thorough understanding of autoantibody production.