Kinetic Aspects of the Removal of IgG and Inhibitors in Hemophiliacs Using Protein A Immunoadsorption

Abstract

Seven patients with hemophilia A and B and 3 patients with acquired hemophilia were treated on 13 and 4 occasions, respectively, with protein A immunoadsorption to reduce anti-factor Vili or IX antibodies. Usually the patients were treated on 2 consecutive days. On each treatment day an average of 3 (range: 1.02-5.83) plasma volumes were processed in the congenital patients and 1.5 (range: 1.02-2.90) in those with acquired hemophilia. Plasma levels of IgG decreased from 18.9 ±1.9 to 3.1±1.2g/l in the congenital group, and from 11.5 ±2.3 to 2.3±0.6g/l in the acquired group. In the congenital hemophiliacs a corresponding reduction in inhibitor level of 70-95% was regularly seen; in 1 exceptional patient the inhibitor was reduced from 4,350 to 12 Bethesda Units/ml (BU/ml) during 5 days of treatment. In the congenital hemophiliacs immunoadsorption was followed by factor infusion to peak levels between 8 and 215 IU/dl. In the patients with acquired hemophilia a satisfactory reduction in inhibitor levels was obtained in 2 of the 4 treatments, which were followed by DDAVP or factor infusion. Some recommendations for the use of protein A immunoadsorption in the treatment of hemophilic patients will be given.

Removal of Immunoglobulins by a Protein A Versus an Antihuman Immunoglobulin G‐Based System: Evaluation of 602 Sessions of Extracorporeal Immunoadsorption

“…Reusable double column immunoadsorption systems are currently available in all European countries and also in the United States. Adsorbents are on a sepharose basis and are used, depending on the ligand, for elimination of IgG (7,9–11) and for low density lipoprotein (13). One of the advantages of these systems is their virtually unlimited adsorption capacity due to simultaneous regeneration and adsorption during 1 therapeutic session.…”

“…IAs have been used succesfully in the treatment of various autoimmune diseases (3–5,7). Other indications were the removal of alloantibodies against human leukocyte antigens (HLA) enabling transplantation (1,8), removal of antibodies enabling xenotransplantation (9), or elimination of antibodies against coagulation factors allowing substitution therapy (10,11).…”

“…According to data sheets and scientific publications, both reusable systems eliminate efficiently Immunoglobulin G (IgG), the immunoglobulin with the highest plasma concentration (10–12). However, whether there are differences between the Excorim and Therasorb system regarding elimination rates and regeneration strategies involving the technical equipment has not yet been examined in a direct clinical comparison.…”

Pathogenic antibody removal using magnetically stabilized fluidized bed

“…Schneider et al studied immunoadsorption plasma perfusion in SLE patients using phenylalanine and tryptophan carrying commercial IM-P columns and reported 2 h treatment time [34]. Some patients with acquired hemophilia have been treated using commercial Immunosorba ® column around 5 h effective treatment time [35] for the removal of IgG and inhibitors. Yu and He investigated the adsorption of anti-dsDNA antibodies in SLE serum on DNA immobilized hydroxyethyl crosslinked chitosan beads and reported that equilibrium adsorption time is 2 h [36].…”

Peptide GAM immunoadsorption therapy in primary membranous nephropathy (PRISM): Phase II trial investigating the safety and feasibility of peptide GAM immunoadsorption in anti‐PLA2R positive primary membranous nephropathy

“…12,15 There is now an increasing body of evidence for the apparent pathogenicity of the anti-PLA 2 R antibodies, with the potential for its use as a biomarker and as a treatment target. [29][30][31] Post-immunoadsorption it appears that autoantibodies can be slow to re-emerge. 15 For patients who go into remission either spontaneously or following immunosuppression, the anti-PLA 2 R level falls months before this becomes clinically apparent with a fall in proteinuria.…”