Treatment of hemophilia patients with inhibitors is most effective if circulating levels of factor VIII (F.VIII) or factor EX (F.IX) can be obtained. This is possible not only in patients with low inhibitor concentration, but also in those with high inhibitor levels after temporary removal of the inhibitors by means of apheresis methods.
Group specific elimination using protein A. This is done by computer controlled extracorporeal adsorption to protein A Sepharose columns of the antibodies in plasma transferred on-line to the plasma treatment apparatus (Citem 10, Excorim, Lund, Sweden). The plasma depleted of inhibitor is returned to the patient together with the seperated blood cells. At the Malmo center, high titer inhibitors have so far been removed in 10 hemophilia patients, and 4 patients with acquired hemophilia, on a total of 25 immunoadsorption episodes. Usually between 2 and 4 plasma volumes were processed in the course of 6 to 12 hours. The inhibitor decreased to zero or very low levels, enabling conventional replacement therapy to be given for control of severe bleeding or as cover for surgery. The treatment is well tolerated and no signs of activation of the coagulation, fibrinolytic, and complement systems were seen.
Specific elimination using coagulation factor. A method has been , developed for the removal of F.IX antibodies directly from whole blood in a continuous extracorporeal system. A F.IX preparation with a specific activity of 92 units per mg protein was covalently coupled to Macro Beaded Sepharose, which allows passage of whole blood. One ml of the absorbent was capable of binding about 2100 BU. The F.IX antibodies could be specifically adsorbed directly from citrated whole blood with a minimal extracorporeal volume. In this way, high-titer antibodies couldbe removed from a boy with hemophilia B, by passing four times his blood volume through the REX column. No side effects were noted. In the future it will be possible to use immobilized F.VIII in a similar system for the removal of F.VIII antibodies.
KeywordsFactor VIII Plasma Exchange Hemophilia Patient Inhibitor Titer Anamnestic Response
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