Factor IX Deficiency in a 2-month Old

An interesting case sent by Sue Hollister:

Hi George,
We recently had an interesting case of a 2-month old who presented with a brain bleed. His PTT was 53 seconds and his factor VIII was normal, but his factor IX was 4%. Looks like a pretty simple case of hemophilia B, however, after treatment with factor IX concentrates, his factor IX did not rise as expected. After 2 months, however, his baseline factor IX was 50%, without treatment.

His other vitamin K factors were within normal range, so that was ruled out, he was not receiving any anticoagulant and he had no underlying health issues. Can you think of anything that can cause this? Thanks!

Hi, Sue. I had to send this one to several expert physicians, and received this message from Dr. Dorothy Adcock, Medical Director at Esoterix Coagulation:

Hi George!
A lupus anticoagulant can interfere with certain intrinsic factors; you may see this effect in one or more intrinsic factors, even when the same reagent is used to test the intrinsic factors.  It would be interesting to know if Sue performed the factor IX activity at multiple dilutions and what the individual results were.  Spontaneous intracranial hemorrhage seems quite unusual for a moderate hemophilia B patient and I wonder if the elevated PTT was a red herring.  Has this child been evaluated for a FXIII deficiency?

Another consideration is transplacental transfer of an antibody, although this would bequite unusual with factor IX, it has certainly been described with FVIII. See Lulla RR, Allen GA, Zakarija A, Green D. Transplacental transfer of postpartum inhibitors to factor VIII. Hemophilia 2009;1-4.

I want to thank Dr. Adcock for her assistance on this and invite others to add their expertise. Sue didn’t mention whether the child continues to have bleeds, however it may be useful to check his factor XIII activity. Although it would be academic at this point, it might also be interesting to learn if the mother had grown an autoanti-factor IX. Geo