Choice of replacement therapy for hemophilia.

Dear Sir,In the February issue of the Journal, Giangrande and Mannucciostensiblytakeoppositesidesonthefollowingsubject:‘Recom-binant factors only? Yes or no?’ [1,2]. In a careful reading oftheir contributions, it is interesting to note that both prefer to userecombinant products for their patients, but both also believethat plasma-derived products should continue to be produced.Giangrande makes the argument that if physicians in developedcountries use recombinant clotting-factor concentrates thenplasma-derived products might well become cheaper and madeavailable to patients in developing or underdeveloped countries.Mannucci makes the same argument in a slightly differentfashion. He points out that since the developing world cannotafford recombinant products, plasma-derived products shouldbe available for the treatment of hemophilic patients in unde-veloped areas of the world.I have long been persuaded that the best choice for treatmentof hemophilic patients is recombinant products. This preferenceis based largely on the belief that clotting factor concentratesprepared by recombinant technology are probably safer thanplasma-derived products because they are manufactured undermore controlled conditions and are not reliant on donor plasmafrom several thousand individuals. Both Mannucci and Gian-grande imply that there is always the possibility that as yetunknown transmissible agents may contaminate the bloodsupply and not be inactivated by current technology. This isprobably the legacy of the AIDS crisis when the hemophilicpopulation was exposed to a transmissible agent that resulted inan incurable disease with exceedingly high morbidity andmortality. None of us wishes to see a repeat of such a colossaltragedy, and, for this reason, many of us are sensitized to thepossibility, no matter how small, of an AIDS-like tragedy in thefuture.Even though many physicians, including myself, preferrecombinant clotting-factor concentrates for the treatment ofpatients with hemophilia, rigid dogmatism that insists upon thesole use of recombinant products may be very unwise sincedogmatism precludes a rational approach to future choice oftherapy for hemophilic patients.Some potential developments in plasma fractionation thatoffer increased yields of cryoprecipitate and factor (F)VIII fromplasma is promising, especially since some might be adaptableto local blood bank technology. Dr Ed Shanbrom and hiscolleagues have recently described a method for obtaining‘supercryo’ [3]. He has found that the yield of cryoprecipitateand FVIII can be increased to approximately 100% by increas-ing the citrate concentration of the starting plasma. More thanthat, the FVIII can be easily extracted from the cryoprecipitate,leaving most of the fibrinogen and von Willebrand factor to beused as a source of fibrin glue. Moreover, it seems feasible thatan iodine column developed by his group to remove infectiousagents might also be adaptable for use in local blood banks toremove infectious particles from FVIII preparations. If suchprocedures are confirmed, they may permit the accessibility ofFVIII concentrates in those parts of the world that cannot affordrecombinant products. It is also interesting that an economicmodel sponsored by Baxter Bioscience but developed indepen-dently by Evans and colleagues suggests that plasma-derivedFVIII and IX concentrates may, in the long run, be economic-ally feasible and safer than currently available cryoprecipitatefractions [4]. The model is ‘evidenced based’ and predicts that‘screened’ cryoprecipitate could be contaminated by infectiousagents not detectable in the window period by currently avail-able screening techniques, including hepatitis viruses, HIV, andother infectious agents. Thus, the patients exposed over alifetime to screened cryoprecipitate could be infected by suchagents.The debate on the source of clotting-factor concentrates forthe treatment of hemophilia, highlighted by Giangrande andMannucci, emphasizes the need to make safe and effectiveclotting factor concentrates available to all hemophilia patients,whatever their geographic location or economic status.References