Influence Of The Antigenic Specificity Of Antiplatelet Antibodies On The Response To Intravenous Immunoglobulin G In Untreated Adults With Severe Primary Immune Thrombocytopenia

Background Primary immune thrombocytopenia (ITP), also referred to as idiopathic thrombocytopenic purpura, results mainly from antiplatelet autoantibodies that mediate platelet clearance in the reticuloendothelial system. Previous studies in murine models of ITP demonstrate that intravenous immunoglobulin G (IVIG) could protect against anti-GPIIb/IIIa-mediated thrombocytopenia while it fails to prevent ITP induced by most anti-GPIb antibodies.Objective The present study was undertaken to ascertain the correlation between the specificity of the antiplatelet antibody and the response to IVIG treatment in adults with severe ITP.Methods The patients met the eligibility criteria previously described by Godeau, et al. as follows:(1) the diagnosis of ITP based on the presence of isolated thrombocytopenia and on the exclusion of other explanations for thrombocytopenia in accordance with the practice guidelines of the American Society of Hematology; (2) age between 18 and 60 years; (3) a platelet count of≤2 x 109/L; and (4) a bleeding score> 8 at the time of admission according to a previously described clinical scoring system by Khellaf to assess the severity of hemorrhage. Patients received 0.4 g of IVIG per kilogram of body weight daily for 5 consecutive days. The criteria for an initial response was a platelet count of 50×109/L or more by day 8 after treatment initiation.Results All of th 87 patients were tested for the presence of IgG antibodies to platelet GPⅡb/Ⅲa and/or GPⅠb/Ⅸbefore treatment. Of the 32 patients who had an antibody against GPⅠb/Ⅸ, only 17 (53.1%) achieved a response, as compared with 47 of the other 55 patients (85.5%) who had no anti-GPⅠb/Ⅸantibody (χ2= 10.8723; p= 0.0010). No significant difference was observed in response between patients (27 out of 40,67.5%) who had an autoantibody to GPⅡb/Ⅲa and those (37 out of 47,78.7%) without anti-GPⅡb/Ⅲa antibodies (x2= 1.3996; p= 0.2368). On further analysis of cross-effects between the specificities of these two antibodies in correlation with the response to treatment, patients were subdivided into 4 groups:patients with autoantibodies specific for GPⅠb/Ⅸalone, GPⅡb/Ⅲa alone, both GPⅠb/Ⅸand GPⅡb/Ⅲa, and antibodies other than GPⅠb/Ⅸand GPⅡb/Ⅲa. The logistic regression analysis revealed that the patients having antibodies directed towards GPⅠb/Ⅸshowed poor response to treatment with IVIG (odds ratio 0.118; 95%C.I.: 0.025-0.564; p=0.0074), whereas the presence of autoantibody to GPⅡb/Ⅲa was not associated with the response to IVIG (p=0.2109). Furthermore, the autoantibodies specific for GPⅡb/Ⅲa could not give rise to effect modification on the antibodies against GPⅠb/Ⅸ, i.e., there was a lack of interaction of anti-GPⅠb/Ⅸwith anti-GPⅡb/Ⅲa in terms of their correlation with the response to IVIG treatment (p= 0.3600).Conclusions The data demonstrated that in adults with severe ITP, the presence of autoantibody to GPⅠb/Ⅸwas an independent predictive factor for poor response to IVIG treatment.