Chronic thrombocytopenia is a common hematologic disorder in patients infected with the human immunodeficiency virus (HIV). Although often asymptomatic, the thrombocytopenia may be associated with a variety of bleeding abnormalities. The underlying pathophysiology includes accelerated peripheral platelet destruction and decreased ('ineffective') production of platelets from the infected megakaryocytes. HIV-related thrombocytopenia (HIV-TP) responds to antiretroviral therapy. Most studies have evaluated the use of AZT (zidovudine) and have shown increased platelet production. Combination therapy (HAART) also resulted in sustained platelet increases. When antiretroviral agents fail to improve the platelet count or cannot be used, other therapies, similar to those used in 'classic' immune thrombocytopenia (ITP), can be employed, including steroids, intravenous immunoglobulin (i.v.intravenous anti-D or splenectomy. Anti-D treatment offers advantages for HIV-TP because the duration of effect appears to be significantly longer than the response duration after i.v. therapy (initial results of our open-arm study were confirmed by our randomized trial). Of note, follow-up of heavily treated patients showed no acceleration of CD4 decline and no change in plasma viral load measurements. Splenectomy has been used to treat HIV-positive patients with refractory thrombocytopenia. Although it is effective therapy, there are concerns about infections and selection of appropriate candidates. Other treatment modalities, such as interferon, vincristine, danazol, low-dose splenic irradiation and staphylococcal protein A immunoadsorption have shown limited success in HIV-TP. Alternatively, thrombocytopenia in HIV-infected patients may be treated with pharmacological hyperstimulation of megakaryocytopoiesis (administration of PEG-rHuMGDF or TPO). Latest evidence indicates that the chemokine receptor CXCR4 (coreceptor for the cellular entry of lymphotropic HIV strains) is expressed on megakaryocytes; as a result, the development of chemokine receptor antagonists may modify the course of the disease.
