Haema 2010; 1(2): 146-156
by Argyris Symeonidis and Alexandra Kouraklis-Symeonidis
Department of Internal Medicine, Haematology Division, University of Patras Medical School, Rion of Patras, Greece.
Abstract
Immune thrombocytopenia (ITP), manifested at the time of initial diagnosis or during disease progression, may accompany various infectious diseases. Infectious agents, which have been pathogenetically associated with ITP are H.Pylorii, Hepatitis C virus and HIV. There are many reports for various other agents, such as CMV, EBV, VZV, HTLV-1, MMR triple vaccine and mycobacterium Tuberculosis. For many additional infectious agents there are only occasional case reports in the literature. In the majority of cases thrombocytopenia is moderately severe (plt count >30 x 109/l) and is rarely accompanied by hemorrhagic episodes. Although the three most common infectious agents have most commonly been associated with adult ITP, a possible contribution in the ITP of childhood has also been postulated. Among the suggested pathogenetic mechanisms, direct infection of the megakaryocytes by the causative agent, immune reaction against proteinic material of the infectious agent, “expressed” on the platelet membrane and extension of the specificity of the antibodies against structural parts of the platelet membrane, adhesion of immune complexes on platelets and increased platelet phagocytosis, and finally cross-reactivity of antigenic determinants of the infectious agent with glycoproteinic epitopes of the platelet membrane, are included. The continuous presence of the infectious agent can establish immunologic memory and specificity of the reaction, and generate specific T- and B-autoreactive clones, perpetuating the autoimmune response. Conversely, when immunologic memory has not been established, elimination treatment of H.Pylorii, shrinkage of hepatitis C viral load, and Highly Active Antiretroviral Treatment for HIV disease are followed by an improvement or restoration of platelet count to normal levels. The pathogenetic role of H.Pylorii has been linked to the expression of a core protein CagA, which shares substantial molecular mimicry with parts of the GPIIβ/III α complex. Other contributing factors are cytokines such as TGFβ, adhesion molecules, such as P-selectin, and genetic factors of the host, such as HLA haplotypes and Lewis antigen expression. For thrombocytopenic patients who are H.Pylorii carriers, response to Helicobacter elimination treatment should initially be evaluated, before any form of immunosuppressive treatment will be administered. It is evident, that screening all thrombocytopenic patients at initial presentation for the three most common infectious agents is mandatory.