Antibodies to plasma proteins: an association with platelet transfusion refractoriness

We hypothesized that antibodies to HLA-linked polymorphic plasma proteins could be involved in platelet refractoriness by an 'innocent bystander' or immune complex mechanism. Employing a kinetic enzyme-linked immunosorbent assay (ELISA) technique the ability of IgG from the plasma of refractory patients to bind to albumin, fibrinogen, complement components C2 and C4 was measured. As compared with controls a high percentage of refractory patients had increased IgG capable of binding to all four plasma proteins: C2 (83%), C4 (83%), albumin (75%), fibrinogen (34%). In the presence of exogenous plasma proteins these antibodies mediated increased deposition of IgG onto normal donor platelets. The plasma protein binding IgG consisted both of monomeric IgG and a broad range of high molecular weight complexes. IgG anti-plasma protein antibody could be eluted from platelets of refractory patients. The development of anti-plasma protein IgG was studied during the course of platelet transfusion therapy and found to increase progressively so that by the 20th transfusion greater than 90% of samples were positive. The presence of plasma protein binding activity correlated with the development of increased levels of platelet bound IgG and refractoriness. Multiple platelet transfusions lead to sensitization to polymorphic determinants on C2 and C4 as well as the formation of high molecular weight complexes. These antibodies and complexes contribute to the deposition of IgG on platelets and may contribute to refractoriness.