Effect of IgG anti‐Rh_o(D) in adult patients with chronic autoimmune thrombocytopenia

Abstract

Seventeen adult patients with chronic (15 cases) or acute (two cases) autoimmune thrombocytopenia (ITP) were given intravenous and/or intramuscular injections of 0.75-4.5 mg of IgG anti-Rho(D) over a period of 1-5 days. Significant elevations of the platelet count (increments greater than 50 X 10(9)/liter) resulted in 13 of 15 Rh-positive patients but not in either of two Rh-negative patients. Heat-aggregated human albumin given to one of the Rh-negative patients also did not lead to a significant increase of the platelet count. The elevation of the platelet counts in Rh-positive patients after IgG anti-Rho(D) administration was often transient (less than 4 weeks), but long-term benefit (greater than 5 months) was achieved in five cases. The IgG concentration on RBC from five Rh-positive patients studied increased from a usually undetectable value before to approximately 700-1,700 IgG molecules/per RBC after anti-Rho(D) administration resulting in a strongly positive direct antiglobulin test. Nevertheless, an overt clinical hemolysis was seen in only one patient. The clearance of autologous 51Cr-labeled RBC was determined in four patients and was slightly enhanced in three and normal in one splenectomized patient. We conclude that the Fc receptor blockade involved in platelet sequestration was not associated with the induction of significant RBC clearance and that a reversible interaction of sensitized RBC with phagocytic cells and/or a low-grade destruction of these cells might be sufficient for the elevation of circulating platelets in the majority of patients with ITP.

Do the acute platelet responses of patients with immune thrombocytopenic purpura (ITP) to IV anti‐D and to IV gammaglobulin predict response to subsequent splenectomy?

“…The patients in the Law study tended to receive IVIG and then proceed to splenectomy within the initial months of their diagnosis of ITP while the patients reported here received the IVIG and especially the splenectomy later in their course (an average of 3 years from diagnosis) and also received IV anti-D. The response rates to the 3 treatments reported here (Table I) are generally consistent with reported response rates [12][13][14][28][29][30], although there is a slightly lower than expected rate of response of children to both IV anti-D (51%) and to splenectomy (68%).…”

“…The published relationship of response to IVIG and response to splenectomy led us to hypothesize that IV anti-D might share a similar relationship, in part because IV anti-D also relies on Fc receptor blockade and also because the response to IV anti-D is clearly affected by whether the patient has been previously splenectomized [13,14,30]. The failure of response to the initial infusion of IV anti-D to predict response to splenectomy was therefore disappointing.…”

The nontreatment of childhood idiopathic thrombocytopenic purpura

“…A new and interesting therapeutic approach, antiRh0(D) globulin, has recently been reported to be effective in adults with acute and chronic forms of ITP. This mode of ther-apy probably induces reticuloendothelial blockade by "saturating" Fc receptors on mononuclear phagocytes with anti-D coated erythrocytes [43]. Further studies of this approach are necessary before it can be recommended for pediatric patients.…”

A GPIIb/IIIa bioreactor for specific treatment of immune thrombocytopenic purpura, an autoimmune disease. Preparation, in vitro characterization, and preliminary proof‐of‐concept animal studies

“…[12][13][14][15][16][17][18] Several new therapeutic modalities are currently under investigation for the treatment of ITP, including 1) application of Protein-A immunoadsorption by using a PROSORBA column 19 ; 2) administration of recombinant thrombopoietin 20,21 ; and 3) administration of immunoglobulin with a high titer of Anti-Rho (D) antibodies. 22,23 Nevertheless, these experimental therapies have all encountered significant shortcomings and risks. For instance, given the evidence that antiplatelet antibodies (APAb) are responsible for the increased rate of PLT destruction observed in ITP, immunoadsorptive plasmapheresis has been developed to accelerate the removal of pathogen antibodies.…”