Effect of Danazol in Immune Thrombocytopenic Purpura

Abstract

Danazol and vinblastine are effective in many patients with chronic immune thrombocytopenic purpura (ITP). To evaluate the mechanism of action of these drugs, we studied six consecutive patients with chronic ITP treated with danazol and one treated with vinblastine. All the patients responded clinically without a notable change in the level of platelet-associated IgG. Instead, the clinical response to therapy was associated with a decrease in the number of monocyte binding sites for monomeric IgG (Fc receptors). In one patient, clinical relapse was associated with a spontaneous 2.7-fold increase in the number of monocyte Fc (IgG) receptors, without a change in the level of platelet-associated immunoglobulin. A decrease in the number of monocyte Fc (IgG) receptors following vinblastine infusion was associated with a clinical remission. We conclude that the clinical course of ITP may be influenced by the expression of monocyte or macrophage Fc (IgG) receptors. Danazol and vinblastine may mediate their clinical effect, at least in part, by influencing the number of available Fc (IgG) receptors on phagocytic cells.

Danazol one Month Treatment of Thrombocytopenia in Chronic Hepatitis C

“…In Alvarez et al study [7] Danazol result in a higher response rates (85%) and higher platelet levels (121081 + 47320/mm3), this could be explained by longer treatment period (2-11 months), higher basal platelet levels as they included levels ≤ 90000/mm3 and also Danazol 600 mg dose with used for patients with platelet level ≤ 60000/mm3 from the start.…”

“…Alvarez et al [7] included 49 patients with chronic HCV and thrombocytopenia ≤ 90000/mm3 because patients were included during Pegylated Interferon (Peg IF) treatment and Danazol was given as long as they were still under treatment to prevent stoppage or decrease anti-viral treatment. In the present study, Danazol 400 mg for one month was given on the basis of least effective and safe dose and also for a short time (one month) to minimize risk of severe or undesirable adverse effects and to facilitate any intervention diagnostic or therapeutic procedures by elevation of platelet levels over a short a short time.…”

“…It's well tolerated treatment of refractory autoimmune thrombocytopenia associated with many autoimmune diseases [7].…”

Modulation of the human monocyte binding site for monomeric immunoglobulin G by activated Hageman factor.

“…Preparation ofmonocytes. We used a method to isolate monocytes in suspension based upon their adherence to serum-treated flasks and their ability to be dislodged in the cold by indirect mechanical means (13,14). Whole blood anticoagulated with sodium heparin was obtained from normal donors and the mononuclear cells isolated by centrifugation on a Ficoll-Hypaque gradient (13).…”

“…The isolated IgG was labeled with 1251I (New England Nuclear, Boston, MA) using chloramine-T followed by Sephadex G-50 chromatography as previously described (13,14) and stored at 4VC until use. Specific activity of the final preparation was 0.16 uCi/gg of protein.…”