Document 0580
 DOCN  M9650580
 TI    Effects of factor VIII concentrates on the immune system of patients
       with hemophilia.
 DT    9605
 AU    Mannucci PM; Angelo Bianchi Bonomi Hemophilia and Thrombosis Center,;
       University of Milan, Italy.
 SO    Thromb Haemost. 1995 Jul;74(1):437-9. Unique Identifier : AIDSLINE
       MED/96116829
 AB    The introduction of high-purity factor VIII (FVIII) concentrates in the
       treatment of patients with hemophilia A has raised the issue that the
       use of these products may change on the immune system of the recipients.
       There is now clear evidence that high-purity concentrates, particularly
       those produced by immune-affinity chromatography or recombinant DNA
       technology, slow the fall in CD4 cells that occurs in HIV seropositive
       patients. It remains to be demonstrated that this biological effect
       results in clinical benefits and that the occurrence of AIDS is slowed
       or delayed by the use of high-purity concentrates. On the other hand,
       concern has been expressed about the possibility that high-purity
       products might render patients with hemophilia less immunotolerant,
       facilitating the onset of FVIII antibodies. Follow-up studies of
       previously untreated hemophiliacs infused for the first time with
       recombinant FVIII products have ignited this concern, because
       approximately one fourth of severe hemophiliacs developed inhibitors.
       However, most of the inhibitors were transient, so that ultimately they
       had little influence on the efficacy of replacement therapy. It was
       subsequently realized that inhibitors develop with high frequency even
       in hemophiliacs treated with less pure, plasma-derived products,
       provided testing is prospective and as frequent as for studies of
       recombinant FVIII. On the whole, these data have provided new insights
       on the natural history of inhibitor development in previously untreated
       hemophiliacs, showing that low-titer, short-lasting inhibitors develop
       more frequently than previously recognized.
 DE    Chromatography, Affinity  CD4 Lymphocyte Count/DRUG EFFECTS  Factor
       VIII/ADVERSE EFFECTS/IMMUNOLOGY/ISOLATION & PURIF/
       *PHARMACOLOGY/THERAPEUTIC USE  Hemophilia/IMMUNOLOGY/*THERAPY  Human
       HIV Infections/PREVENTION & CONTROL/TRANSMISSION  Immune System/*DRUG
       EFFECTS  Immune Tolerance/DRUG EFFECTS
       Isoantibodies/BIOSYNTHESIS/IMMUNOLOGY  Recombinant Proteins/ADVERSE
       EFFECTS/PHARMACOLOGY/THERAPEUTIC USE  Safety  JOURNAL ARTICLE  REVIEW
       REVIEW, TUTORIAL

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