Hemolysis after intravenous immune globulin therapy: relation to IgG subclasses of red cell antibody

Abstract

A patient with chronic idiopathic thrombocytopenic purpura (ITP), a 28-year-old group A, Rh-positive woman, also had hemolytic anemia. At that time, her red cells typed as group A, but the serum typed as group O. This typing followed intravenous high-dose immune globulin therapy, (400 mg/kg for 5 successive days) and was attributable to A antibody of the IgG type, composed of IgG1, IgG2, IgG3, and IgG4, in the immune globulin preparation, which had been given for treatment of ITP. All lots of commercial human plasma preparation products (heat-treated human plasma protein, albumin, factor VIII or IX products, and immune globulin) examined were found to contain A and/or B antibodies of the IgM or IgG type, with titers of 1 to 1024. Twelve of the 20 lots of immune globulin contained RBC antibodies of the IgG type. Subclass IgG1 was found in all 12 of these lots, and all four subclasses, including IgG3, were detected in 8 lots. All 8 showed antibody titers higher than 64.

Isoantibodies in Immunoglobulin for Intravenous Use May Cause Erythrocyte Sequestration

“…In the preparation of IVIg, these IgG isoantibodies form part of the pooled IgG. Although the titers of IgG isoantibodies in IVIg have not, for the most part, been considered a problem, there have been reports of hemolysis subsequent to IVIg in type A or B recipients [15, 16]. We have shown that the anti–A and anti–B in IVIg are sufficient to bind to RBC and mediate erythrophagocytosis.…”

“…Such treatment can bring about subclinical sequestration of erythrocytes in normal healthy persons [9], and can induce [11, 12, 13, 14, 16, 17, 18, 19, 24, 25]or exacerbate hemolytic anemia in treated patients [9, 10, 15]. …”

“…These include enhanced, though subclinical, erythrocyte sequestration in healthy persons [9], and augmented red cell turnover in patients undergoing treatment for idiopathic thrombocytopenic purpura (ITP) [9, 10]and other diseases [11, 12, 13], as well as in anemic patients [10, 14, 15]. There have also been rare reports of massive intravascular hemolysis associated with IVIg treatment [16], and of hemolytic anemia following IVIg treatment [14, 17, 18, 19].…”

“…Erythrophagocytosis has not been examined experimentally at the concentrations of IVIg reached in treatment of patients with high doses of IVIg. This study was undertaken to determine whether the presence of red cell antibodies at the concentrations present in IVIg can enhance in vitro erythrophagocytosis and thus potentially participate in the augmented erythrocyte sequestration observed in certain patients after exposure to IVIg [9, 10, 14, 15, 16, 17, 18, 19]. …”

Intravenous immune globulins: an update for clinicians

“…Thus RBC antibodies have been found in 49 percent of 165 lots of IVIG, including anti‐K, ‐C, and ‐Le b 160 . Most antibodies detected in IVIG are low titer (<1:16, using a saline method; <1:1024 using an antiglobulin method) 171,172 . Nonetheless, positive antibody screens and DATs in patients treated with IVIG are seen, although limited in duration (2‐5 days) 173 ‐175 .…”