Substitution Therapy in Haemophilia B^[*]

Conclusions

1. Substitution therapy in haemophilia B without daily control of the Factor IX level in vivo by means of a reliable Factor IX assay cannot be adequate.

2. The level of the Factor IX activity which, in cases of haemophilia B, ensures safe haemostasis after major trauma or in major surgery is at least 25% of normal.

3. Assuming a normal t½ for Factor IX of 30 hours and a distribution pool of 7 l (normal adult), in cases of severe haemophilia the minimum amount of Factor IX to be rapidly transfused at the beginning of substitution (loading up of the pool up to 25%) is the amount present in 1.75 l of freshly drawn normal net plasma. The minimum daily dose necessary to maintain the 25% level is contained in 1 l. Due to the influence of body temperature, the required daily maintenance dose increases probably up to 2.4 l.

4. Since rapid infusion of more than 1 l net plasma is not tolerated and since a daily dose of 2.4 l net plasma can hardly be achieved by means of exchange transfusion, partially purified and concentrated human Factor IX must be available. The plasma product PPSB, prepared by the “Centre National de Transfusion Sanguine” in Paris, contains, according to in vivo assays, about 10 times the activity of normal plasma for comparable volumes. The t½ of the Factor IX from PPSB appeared to be the same as from fresh plasma. The disappearance rate of the concentrated Factor IX from serum (CSB), prepared by the same institute, has not been estimated experimentally. According to clinical experience, however, the activity of CSB seems to be of a similar magnitude as that of PPSB. Adequate substitution with PPSB alone would require as initial loading-up dose 175 ml and as daily maintenance dose 100—240 ml of a 10-fold concentrated product, to be given in a continuous drip-infusion.

5. In a case of mild haemophilia B (Factor IX ≅ 20%), transfusion of 0.8 l freshly drawn net plasma daily resulted in Factor IX levels of between 23 and 28% instead of the expected 35% of normal. This observation suggests that, for substitution therapy, mild cases of haemophilia B must be considered as rather severely affected.

^* Synonyms: antihaemophilic factor B (AHF B)- or antihaemophilic globulin B (AHG B)- or factor IX- or plasma thromboplastin component (PTC)- deficiency; Christmas disease.

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