Platelet antibodies in immune thrombocytopenia

Abstract

Several tests to detect antibodies to platelets in patients with immune thrombocytopenia have been developed over the 40 years since it was first noted that this disorder was mediated by antiplatelet factors. Early tests were crude and not reproducible. A major landmark was the quantitation of IgG immunoglobulin on platelet membrane and the observation by several workers that marked increases of all classes of immunoglobulin occurred on platelets in patients with immune thrombocytopenia. Although at one time accepted as a diagnostic characteristic of autoimmune thrombocytopenia (AITP), the initial euphoria was tempered over the last decade by the realisation that elevation of platelet associated immunoproteins was not pathognomonic of this disorder and that raised levels were seen in several other disease processes, sometimes even when platelet counts were normal. The nature of these immunoproteins needs careful understanding. True platelet autoantibodies will manifest as increased platelet immunoproteins but not all such platelet proteins are platelet antibodies. There is speculation about the existence and the mode of activity of IgA and IgM immunoglobulins, both commonly found on platelets in AITP. It is sometimes almost inconceivable that the extremely large amounts of PAIgG could possibly represent true autoantibody. Immune complexes are found in plenty in these and other disorders in which thrombocytopenia manifest. In such situations it is likely that ‘amplified’ immune complexes are bound by Fc receptors, as may be found in viral mediated ITP or in septicaemic states. There is now sound evidence that several glycoprotein such as GP IIb IIIa , GP Ib, GP V, found on platelet membrane, act as target antigen sites for the attachment of antibodies to platelets. Immunoblot techniques have done much to elucidate these properties. Arising from this knowledge a new generation of tests have now been developed, such that it is possible to detect and quantify autoantibodies that are specific to these antigens. The different techniques for these new tests do not as yet necessarily detect all such antibodies and there remains some disagreement between laboratories in the results that are obtained. As yet these tests have not been shown to cast light on the clinical course of individual patients nor have they been of help in determining therapy. Much collaborative work is underway currently and it is hoped that in time such answers will follow.