Effects of factor VIII concentrates on the immune system of patients with hemophilia.
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.
Mannucci
P M
PM
Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, University of Milan, Italy.
D018791:CD4 Lymphocyte Count / Q000187:drug effects; D002846:Chromatography, Affinity; D005169:Factor VIII / Q000009:adverse effects / Q000276:immunology / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D015658:HIV Infections / Q000517:prevention & control / Q000635:transmission; D006467:Hemophilia A / Q000276:immunology / Q000628:therapy*; D006801:Humans; D007107:Immune System / Q000187:drug effects*; D007108:Immune Tolerance / Q000187:drug effects; D007518:Isoantibodies / Q000096:biosynthesis / Q000276:immunology; D011994:Recombinant Proteins / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D012449:Safety
D007518:Isoantibodies; D011994:Recombinant Proteins; D005169:Factor VIII