Association of FC Gamma RIIIA Polymorphism and Thrombopoietin (THPO) Expression With Response to TPO Agonists in Refractory ITP and the Impact of Therapy on B and T Cells Subsets in the Patients With Mutated Genotypes

Immune thrombocytopenic purpura (ITP) is a autoimmune disorder in which a decreased number of circulating platelets (thrombocytopenia) manifests as a bleeding tendency, easy bruising (purpura), or extravasation of blood from capillaries into skin and mucous membranes (petechiae).

In persons with ITP, platelets are coated with autoantibodies to platelet membrane antigens, resulting in splenic sequestration and phagocytosis by mononuclear macrophages. The resulting shortened life span of platelets in the circulation, together with incomplete compensation by increased platelet production by bone marrow megakaryocytes, results in a decreased platelet count.

In immune thrombocytopenic purpura (ITP), an abnormal autoantibody, usually immunoglobulin G (IgG) with specificity for one or more platelet membrane glycoproteins (GPs), binds to circulating platelet membranes to induce clinically significant platelet dysfunction by directly blocking access of agonists to platelet Gp receptors.

Autoantibody-coated platelets induce Fc receptor-mediated phagocytosis by mononuclear macrophages, primarily but not exclusively in the spleen. The spleen is the key organ in the pathophysiology of ITP, not only because platelet autoantibodies are formed in the white pulp, but also because mononuclear macrophages in the red pulp destroy immunoglobulin-coated platelets.

Polymorphisms in FcγRIIIA have been implicated in responsiveness to splenectomy, corticosteroids and rituximab. Current trial is designed to investigate the impact of genetic predisposition of FcγRIIIA polymorphisms in refractory ITP patients treated with Eltrombopag along with cytokine profile expression in responders and non responders.