Inhibition of platelet-aggregating activity in thrombotic thrombocytopenic purpura plasma by normal adult immunoglobulin G.

Abstract

Abstract. Plasma from patients with thrombotic thrombocytopenic purpura (TTP) caused the aggregation of autologous and homologous platelets, an effect which was inhibited by normal plasma. IgG purified from seven normal adults at a concentration of 0.7 mg/ ml completely inhibited the platelet aggregation induced by plasma obtained from two TTP patients with active disease. The inhibition of platelet aggregation by human adult IgG was concentration dependent, and the inhibitory activity of human IgG was neutralized by rabbit antihuman IgG. Fab fragments inhibited the TTP plasmainduced platelet aggregation as well as intact IgG, whereas Fc fragments had no effect. Platelet aggregation caused by ADP, collagen, epinephrine, or thrombin was not affected by purified human IgG. The prior incubation of IgG with TTP plasma caused a significantly greater reduction of platelet aggregation by TTP plasma than that of IgG and platelet suspension, suggesting that the IgG inhibits TTP plasma-induced platelet aggregation through direct interaction with platelet aggregating factor in TTP plasma.IgG obtained initially from five infants and young children under the age of 4 yr did not possess any inhibitory activity. When one of the children reached 3 yr of age, his IgG inhibited the aggregation induced by one TTP plasma, but not that caused by another plasma. The IgG procured from the same boy at 4 yr of age inhibited the aggregation induced by both TTP plasmas. The IgG purified from the TTP plasma during active disease failed to inhibit the aggregation caused by the same plasma. After recovery, however, the IgG effectively inhibited aggregation. These observations suggest that platelet-aggregating factors present in the TTP plasma are heterogeneous in nature and that the IgG present in the normal adult plasma, which inhibits the TTP plasma-induced platelet aggregation, may be partially responsible for the success of plasma infusion therapy in TTP.

Efficacy of Intravenous Immunoglobulin in the Treatment of Thrombotic Thrombocytopaenic Purpura

“…However, their efficacy has not been clearly shown yet. The rationale for the use of immunoglobulins was based on the following: (a) It had been previously shown that both homologous and autologous platelet aggregation by plasma of TTP patients can be inhibited by normal adult IgG in vitro [11, 12], and (b) There had been sporadic cases published in the literature reporting the efficacy of ivIgG in inducing remission in TTP patients who had previously failed on the standard treatment with plasma exchange [13, 14, 15, 16, 17]. …”

Thrombotic Thrombocytopenic Purpura: Report of a Case with a Possible Response to High-Dose Intravenous Gamma Globulin

“…The mechanism of action of plasma and plasmapheresis still remains obscure. In some pa tients serum factors that cause aggregation of normal control platelets have been isolated and may have pathogenetic significance as they disappear during periods of remission [2], In addition, these platelet aggregating factors can be inhibited by normal plasma or plasma from TTP patients obtained during remissions. It is uncertain whether plasma therapy re moves such serum platelet aggregating factors, dilutes these factors or may be supplying an inhibitor of them.…”

Intravenous Gamma Globulin in Refractory Thrombotic Thrombocytopenic Purpura

“…Its use in vivo was based on the inhibitory effect in vitro of human Ig on platelet aggregation induced by plasma of TTP patients [13], Although recent studies did not confirm the usefulness of HDIg in the manage ment of TTP [10,11 ], or suggested the possibility of a del eterious effect of this therapy [ 14], in our patient the treat ment was effective and not harmful. This was the only patient we have treated with HDIg, because she was the only one refractory to all other therapies.…”