Use of intravenous immunoglobulins in haematological disorders

With many controlled clinical trials and well documented case reports, therapy with intravenous immunoglobulins (IVIg) is now used as a major or adjuvant therapeutic modality in a great number of haematological diseases, Immune-mediated peripheral cytopenias with severe clinical complications may require instantaneous improvement and, generally, the response to high doses of IVIg is more rapid than that to corticosteroids, As a rule, the acute forms of idiopathic thrombocytopenic purpura (ITP) respond more consistently than the chronic forms, in which the response to IVIg is more transient. The immunopathogenic mechanisms leading to cytopenia crucially influence the response; for example, ITP due to HIV infection is more resistant to IVIg than acute ITP due to other viral infections or the purely idiopathic forms. Diseases with overt humoral autoimmunity against blood cells and/or against their precursors probably respond to IVIg because of antibody species contained in the preparations which act at various levels of disturbed immunity. Important activities of IVIg with therapeutic potential include: (a) downregulation of the multifaceted Fc receptor function; (b) deviation of complement activation to innocuous targets; (c) inhibition of autoantibody activity through V region-dependent interaction between therapeutic and recipient immunoglobulins; and (d) regulation of disturbed cytokine networks. In addition to its direct action on basic autoimmune processes, IVIg is also used for malignant haematological diseases. In these situations, we use IVIg not to treat the basic disease, but to improve disease-specific and/or iatrogenic immunodeficiency. Thus, patients with lymphoproliferative disorders, if subject to repeated infectious episodes, may benefit from long term therapy with the antimicrobial antibodies contained in IVIg. Similarly, patients treated with long term plasma exchange often need IVIg to correct the postpheresis syndrome of hypogammaglobulinaemia if IVIg is not given in higher doses in combination with plasma exchange for a synergistic effect. Haematologists should be aware of the costs and potential adverse effects of IVIg therapy. IVIg costs $US30 to $US50 per gram, depending on the preparation in use. A few reported cases of virus transmission were confined to insufficiently controlled production batches, and this much-feared adverse effect of blood products virtually does not apply to modern IVIg preparations. However, IVIg must be administered with caution to patients with cardiovascular and/or renal problems.