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Blood, 15 February 2004, Vol. 103, No. 4, pp. 1364-1369.
Prepublished online as a Blood First Edition Paper on October 23, 2003; DOI 10.1182/blood-2003-08-2672.
 Previous Article | Table of Contents | Next Article 
HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY
Suppression of in vitro megakaryocyte production by antiplatelet autoantibodies from adult patients with chronic ITP
Robert McMillan,
Lei Wang,
Aaron Tomer,
Janet Nichol, and
Jeanne Pistillo
From The Scripps Research Institute, La Jolla, CA; Ben-Gurion University of the Negev, Beer-Sheva, Israel; and Amgen Inc, Thousand Oaks, CA.
Chronic immune thrombocytopenic purpura (ITP) is manifested by autoantibody-induced platelet destruction. Platelet turnover studies suggest that autoantibody may also affect platelet production. To evaluate this, we studied the effect of plasma from adult patients with chronic ITP on in vitro megakaryocyte production. CD34+ cells, obtained from healthy donors, were cultured in medium containing PEG-rHuMGDF and 10% plasma from either ITP patients or healthy subjects. Cultures containing plasma from 12 of 18 ITP patients showed a significant decrease (26%-95%) in megakaryocyte production when compared with control cultures. Positive ITP plasmas not only reduced the total number of megakaryocytes produced during the culture period but also inhibited megakaryocyte maturation, resulting in fewer 4N, 8N, and 16N cells. The role of antibody in this suppression is supported by 2 factors: (1) immunoglobulin G (IgG) from ITP patients inhibited megakaryocyte production when compared with control IgG; and (2) adsorption of autoantibody, using immobilized antigen, resulted in significantly less inhibition of megakaryocyte production when compared with unadsorbed plasma. These results show that plasma autoantibody from some adult patients with ITP inhibits in vitro megakaryocyte production, suggesting that a similar effect may occur in vivo.
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