Thrombocytopenia is common at all stages of HIV disease and may be the presenting feature. In many patients, an immune basis is strongly suggested by the presence of normal or increased numbers of megakaryocytes in the bone marrow, by the presence of platelet-associated IgG and complement in a high proportion of patients studied, and by the response to conventional treatment for immune thrombocytopenic purpura (ITP). However, thrombocytopenia in HIV disease may also result from marrow impairment, toxic drug effects or the effects of splenomegaly.
The specific mechanism of platelet autoimmunity remains unclear. Higher levels of platelet-bound IgG and complement are seen in HIV-related ITP than in classic ITP, and circulating immune complexes capable of binding normal platelets can be found in the serum. In contrast with classic ITP, the eluates of the platelet-associated immunoglobulins in HIV-associated ITP react against normal platelets in only a minority of patients. In HIV patients, unlike patients with classic ITP, platelet counts are not inversely related to platelet-bound IgG, although it is likely that the deposition of immune complexes leads to increased peripheral destruction of platelets by phagocytic cells. The nature of the immune complexes has been extensively studied. They lack HIV antigen and proviral DNA but contain anti-HIV gp120 and anti-antibodies directed against the anti-HIV antibodies. In some patients cross-reactivity of antibodies against HIV gp120/gp160 with platelet glycoprotein GPIIb/IIIa has been demonstrated.
Platelet kinetic measurements suggest that, in addition to peripheral platelet destruction, ineffective thrombopoiesis is a factor in producing thrombocytopenia in HIV-infected patients, and this may result from the deposition of immune complexes on megakaryocytes, invasion of megakaryocytes by HIV or thrombopoietic inhibitors induced by HIV. The commonly observed dysplastic changes in the megakaryocyte series suggest that dysplasia is an important cause of ineffective platelet production and may be the dominant factor in the thrombocytopenia of advanced HIV disease.
Thrombotic thrombocytopenic purpura has been described in HIV disease and responds to conventional treatment with plasma exchange. The pathophysiology is unclear, although it has been postulated that immune complex damage to platelets and endothelial cells is contributory.
Immune thrombocytopenia in HIV disease does not increase the risk of progression to AIDS so should not be viewed as an indicator of poor prognosis. The response to conventional treatment for ITP does not differ from classic ITP, although the approach to treatment is affected by the presence of HIV infection. Prednisolone is not satisfactory as a first-line treatment because of the risk of potentiating or reactivating infections. If other treatments fail, then prednisolone therapy should be covered with prophylactic antimicrobials against Pneumocystis carinii and mycobacteria, at least in patients with significantly reduced CD4 counts. Intravenous immunoglobulin is effective in HIV-related ITP and should probably be the first-line treatment, although the effect is usually only transient. Many patients, however, do not need active treatment and a conservative approach is justified, with intervention only if bleeding occurs, if an invasive procedure is planned, or if the platelet count is judged to be perilously low. Platelet transfusion may permit an adequate, if short-lived, increment sufficient to allow an investigative procedure such as endoscopic biopsy or lumbar puncture.
Splenectomy improves the platelet count in the majority of patients, but may not be justified in a person with advanced HIV disease. It does, however, have a role to play in the management of severe and troublesome ITP in the earlier stages of HIV disease, and there is no evidence that splenectomy contributes to the development of AIDS.
Some patients with HIV-associated thrombocytopenia respond to antiretroviral therapy. This effect was first described using zidovudine, but other agents may have a similar effect. It is likely that antiretroviral treatment exerts its effect by permitting more effective platelet production rather than by decreasing peripheral platelet destruction, thereby emphasizing the two mechanisms involved in HIV-associated thrombocytopenia.
Intravenous anti-D immunoglobulin is effective in a high proportion of RhD-positive patients with ITP and is generally well tolerated, with significant immune haemolysis being uncommon. The mode of action is likely to be Fc receptor blockade by anti-D-coated red blood cells. Patients who have been splenectomized have a much lesser chance of response as the spleen is the primary site of removal of antibody-coated cells.
Other treatment options in HIV-related ITP include danazol, vincristine, interferon-a and extracorporeal immunoabsorption; all have limited success.
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