Relative Efficacy of Steroid Therapy in Ameliorating Autoimmune Thrombocytopenia Mediated by Anti-Platelet GPIIbIIIa Versus GPIbα Antibodies.

Idiopathic thrombocytopenic purpura (ITP) is a common autoimmune disease characterized by autoantibody-induced platelet destruction and consequent bleeding disorders. Despite considerable investigation, the pathogenesis of ITP remains incompletely understood, and we currently lack a consensus for therapy. The major targeted platelet autoantigens are located on two distinctive platelet receptors; the GPIIbIIIa and GPIb complexes. It has been reported that thrombocytopenia induced by anti-GPIba antibodies, which may differ from that induced by anti-GPIIbIIIa, can be mediated via an Fc-independent pathway. We further demonstrated in a murine model that anti-GPIba-mediated-ITP is less responsive to IVIG treatment (Blood. 2006; 108(3):943-6), which is consistent with a subsequent retrospective study in human ITP patients. Since IVIG is expensive and steroid therapy is the first line of treatment for most patients, particularly in developing countries, we tested whether gluococorticosteroid therapy has equal efficacy in ITP patients caused by these two different antibodies.

A total of 107 ITP patients (71 females and 36 males) were recruited for the present study. Patients were first treated with Dexamethasone (DXM, 20mg/day x 3-5 days), then changed to oral administration of Prednisone (1mg/kg/day). The dose of Prednisone was gradually decreased and maintained for = 30 days. The patients were considered as responders to the therapy if no obvious haemorrhage was detected and their platelet counts were raised to = 50 × 109/L or increased by = 30 × 109/L from their original platelet count before treatment. All patients' plasma samples were collected before therapy and specific autoantibodies against GPIIbIIIa and/or the GPIb complex were measured with a monoclonal antibody immobilization of platelet antigen assay (MAIPA).

Among the 107 patients, 23% (25/107) had antibodies against GPIIbIIIa, 18% (19/107) had antibodies against the GPIb complex, 34% (36/107) had antibodies against both the GPIIbIIIa and GPIb complex, and 25% (27/107) had no detectable antibody to either of these two antigens. We found that a majority of the patients with antibodies against GPIIbIIIa (15/22) were sensitive to the steroid therapy, which is significantly different from those with antibodies against the GPIb complex (5/19) (X2 = 7.15, P <0.01) or those with antibodies against both the GPIb complex and GPIIbIIIa (6/34) (X2 = 14.5, P <0.01). Although no statistically significant difference was observed between patients with anti-GPIb antibodies and those with both anti-GPIb and anti-GPIIbIIIa antibodies (X2 = 0.55, P >0.05), there is a tendency that patients with double positive antibodies were less responsive to steroid therapy therapy. The most sensitive patients for this therapy were those without detectable antibodies to either of these two autoantigens (21/27).

Our data suggest that anti-GPIb-mediated ITP may be less responsive to both IVIG and steroid therapies when compared to anti-GPIIbIIIa-mediated ITP. The pathogenesis and treatment of anti-GPIb-mediated ITP merits further investigation.

No relevant conflicts of interest to declare.