Attempt to improve the diagnosis of immune thrombocytopenia by combined use of two different platelet autoantibodies assays (PAIgG and MACE)

Abstract

BACKGROUND AND OBJECTIVES: Despite an extensive search for a definitive diagnostic assay for platelet autoantibodies, the laboratory diagnosis of immune thrombocytopenia (ITP) still remains a clinical challenge. Data in the literature have so far demonstrated that measurement of platelet-associated IgG (PAIgG) is sensitive, especially when flow cytometry is employed, but lacks adequate specificity. Measuring specific autoantibodies by antigen capture techniques increases specificity, but a large part of patients escape autoantibodies detection by such means too. The aim of the present study was to compare the diagnostic value of PAIgG with a modified antigen capture ELISA (MACE) in patients with primary and secondary immune thrombocytopenia and in patients with non-immune thrombocytopenia. DESIGN AND METHODS: One hundred and four patients with a platelet count lower than 100x109/L were studied. Forty-two patients had primary ITP (P-ITP), 23 patients had ITP secondary to other immune diseases (S-ITP) and 39 patients had thrombocytopenia due to decreased platelet production (non-immune; NITP). PAIgG was measured by immunofluorescent flow cytometry, whereas specific platelet-associated autoantibodies (against GP IIb/IIIa, Ib/IX, Ia/Ia) were measured by a commercially available modified antigen capture assay (MACE, GTI, USA). RESULTS: The sensitivity of the PAIgG assay for ITP was 60%, the specificity was 77%, the positive predictive value was 81% and the negative predictive value was 54%. The sensitivity of MACE was 60%, specificity was 97%, the positive predictive value 97% and the negative predictive value 59%. We found a 73% concordance between PAIgG and MACE assays. Both PAIgG and MACE had significantly greater sensitivity in S-ITP than in P-ITP. INTERPRETATION AND CONCLUSIONS: Forty percent of patients with clinically diagnosed immune thrombocytopenia had no detectable platelet autoantibodies, possibly because of intrinsic methodological detection problems, different stages of disease, or absence of a true immune etiology.