Subscribe to RSS
DOI: 10.1160/TH03-07-0430
Extracorporeal adsorption of anti-Factor VIII allo-antibodies on randomly functionalized polystyrene resins
Publication History
Received
02 July 2003
Accepted after revision
30 October 2003
Publication Date:
01 December 2017 (online)
![](https://www.thieme-connect.de/media/10.1055-s-00035024/200402/lookinside/thumbnails/10-1160-th03-07-0430-1.jpg)
Summary
The occurrence of anti-factor VIII (FVIII) allo-antibodies is a severe complication of the treatment of haemophilia A patients, leading to the inhibition of transfused FVIII activity. The effective elimination of these inhibitory antibodies plays a decisive role in the management of affected patients. To achieve this, immunoadsorption devices employing synthetic adsorbers, which selectively eliminate inhibitors, are of interest in the treatment strategy of haemophilia A patients with inhibitors. Adsorbers consisting of polystyrene-based beads substituted with sulphonate and L-tyrosyl methylester groups, which mimic part of epitope of FVIII molecule recognized by inhibitors, exhibit selective binding capacities towards anti-FVIII antibodies. The adsorption of FVIII inhibitors was investigated by simulating an extracorporeal circulation of haemophilic plasma over these functionalized resins. These innovative adsorbers are able to remove around 25% of anti-FVIII antibodies in 15 minutes depending on the plasma tested. Furthermore, they do not modify the amount of essential plasmatic proteins or residual immunoglobulins G. Experiments which were carried out using different plasmas with various inhibitor titres demonstrate a good reproducibility regarding the adsorption capacity of the synthetic resin. The characteristics of adsorption are similar on either native or regenerated resins. Both the purely synthetic nature of the resin and its easy processability demonstrate the real advantages over currently available protocols. This synthetic adsorber is a major technological advance in selective removal of FVIII inhibitory antibodies.
-
References
- 1 McMillan CW, Shapiro SS, Whitehurst D. et al. The natural history of factor VIII:C inhibitors in patients with hemophilia A: a national cooperative study. II. Observations on the initial development of factor VIII:C inhibitors. Blood 1988; 71 (02) 344-8.
- 2 Lusher J. Inhibitor antibodies to Factor VIII and Factor IX: Management. Seminars in Thrombosis and Hemostasis 2000; 26 (02) 179-88.
- 3 Aledort L. Inhibitors in hemophilia patients: current status and management. Am J Hematol 1994; 47 (03) 208-17.
- 4 Kasper CK, Aledort L, Aronson D. et al. Proceedings: A more uniform measurement of factor VIII inhibitors. Thromb Diath Haemorrh 1975; 34 (02) 612.
- 5 Brackmann HH, Lenk H, Scharrer I. et al. German recommendations for immune tolerance therapy in type A haemophiliacs with antibodies. Haemophilia 1999; 05 (03) 203-6.
- 6 Fulcher CA, de Graaf Mahoney S, Zimmerman TS. FVIII inhibitor IgG subclass and FVIII polypeptide specificity determined by immunoblotting. Blood 1987; 69 (05) 1475-80.
- 7 Prescott R, Nakai H, Saenko EL. et al. The inhibitor antibody response is more complex in hemophilia A patients than in most nonhemophiliacs with factor VIII autoantibodies. Recombinate and Kogenate Study Groups. Blood 1997; 89 (10) 3663-71.
- 8 Kulkarni R, Aledort LM, Berntorp E. et al. Therapeutic choices for patients with hemophilia and high-titer inhibitors. Am J Hematol 2001; 67 (04) 240-6.
- 9 Huestis DW, Morrison FS. Adverse clinical effects of immune sorption with staphylococcal protein A columns. Transfus Med Rev 1996; 10 (01) 62-70.
- 10 Freiburghaus C, Berntorp E, Ekman M. et al. Immunoadsorption for removal of inhibitors: update on treatments in Malmo-Lund between 1980 and 1995. Haemophilia 1998; 04 (01) 16-20.
- 11 Jansen M, Schmaldienst S, Banyai S. et al. Treatment of coagulation inhibitors with extracorporeal immunoadsorption (Ig-Therasorb). Br J Haematol 2001; 112 (01) 91-7.
- 12 Dahri L, Boisson-Vidal C, Regnault V. et al. Synthetic sorbents for removal of factor VIII inhibitors from haemophilic A plasma. J Chromatogr B Biomed Appl 1995; 664 (01) 47-54.
- 13 Cornelius RM, Dahri L, Boisson-Vidal C. et al. Adsorption of immunoglobulin G and antifactor VIII inhibitory antibody from haemophiliac plasma to derivatized polystyrenes. Biomaterials 1997; 18 (05) 429-36.
- 14 Shima M, Fulcher CA, de Graaf Mahoney S. et al. Localization of the binding site for a factor VIII activity neutralizing antibody to amino acid residues Asp1663-Ser1669. J Biol Chem 1988; 263 (21) 10198-203.
- 15 Lubin IM, Healey JF, Barrow RT. et al. Analysis of the human factor VIII A2 inhibitor epitope by alanine scanning mutagenesis. J Biol Chem 1997; 272 (48) 30191-5.
- 16 Healey JF, Lubin IM, Nakai H. et al. Residues 484-508 contain a major determinant of the inhibitory epitope in the A2 domain of human factor VIII. J Biol Chem 1995; 270 (24) 14505-9.
- 17 Dahri L, Boisson-Vidal C, Muller D. et al. Tyrosyl sulfamide derivatives as ligands for affinity adsorption of anti FVIII antibodies. J Biomater Sci Polym Ed 1994; 06 (08) 695-705.
- 18 Caron C, Dautzenberg MD, Delahousse B. et al. A blinded in vitro study with Refacto mock plasma samples: similar FVIII results between the chromogenic assay and a one-stage assay when using a higher cephalin dilution. Haemophilia 2002; 08 (05) 639-43.
- 19 Clauss A. Quick method to estimate fibrinogen by a functional clotting assay. Acta Haematol 1957; 17: 237-46.
- 20 Jones BM. The quantification of alternative pathway complement function by timed lysis assay. J Immunol Methods 1979; 29 (03) 287-92.
- 21 Boisson-Vidal C, Haouam M, Lakhiari H. et al. Polystyrene derivatives as candidates for extracorporeal adsorption of Factor VIII antibodies in the management of haemophiliac patients. Vox Sang 2002; 83 (03) 214-21.
- 22 Horbett TA, Brash JL. Proteins interfaces II: Fundamentals and applications. 1995
- 23 DiMichele DM, Kroner BL. The North American Immune Tolerance Registry: practices, outcomes, outcome predictors. Thromb Haemost 2002; 87: 52-7.
- 24 Nilsson IM, Jonsson S, Sundqvist SB. et al. A procedure for removing high titer antibodies by extracorporeal protein-A-sepharose adsorption in hemophilia: substitution therapy and surgery in a patient with hemophilia B and antibodies. Blood 1981; 58 (01) 38-43.
- 25 Kronwall G, Williams RDJ. Difference In antiprotein A activity among IgG subgroups. J Immunol 1969; 103: 828-11.
- 26 Nilsson IM. The management of hemophilia patients with inhibitors. Transfus Med Rev 1992; 06 (04) 285-93.
- 27 Knobl P, Derfler K. Extracorporeal immunoadsorption for the treatment of haemophilic patients with inhibitors to factor VIII or IX. Vox Sang 1999; 77 (Suppl. 01) 57-64.
- 28 Watt RM, Bunitsky K, Faulkner EB. et al. Treatment of congenital and acquired hemophilia patients by extracorporeal removal of antibodies to coagulation factors: a review of US clinical studies 1987-1990. Transfus Sci 1992; 13: 233-53.
- 29 Hieppe F, Wolbart K, Schlosser W. Development of a DNA-adsorbent for the specific removal of anti-DNA autoantibodies in SLE. Biomater. Artif Cells Artif Organs 1990; 18: 683-8.
- 30 Zeuner F, Beress R, Schroeder J. Effect of an antigen-specific immunoadsorption on antibody kinetics in a rat model. Artif Cells Artif Organs 1993; 199-211.