By Dr. David Clark

6/24/24  Hemophilia B suffers from having too few patients as subjects for research.  Because of that, some of the knowledge about hemophilia B is extrapolated from studies of hemophilia A.  

We figure that the disorders are similar enough that what is true for A might also be true for B.  This is even more so the case for inhibitor research where there are even fewer B inhibitor patients.  We’ve thought that this is the best we can do because of the limited resources and numbers of inhibitor patients available for B.

At ISTH, a group from China looked at the immune responses that cause hemophilia patients to develop inhibitors.  They did gene sequencing of individual peripheral blood mononuclear cells (PBMCs) from hemophilia A and B inhibitor patients, a truly tedious but useful undertaking.  

PBMCs are white blood cells that are part of the immune system.  They found unexpected differences.  B inhibitor patients had higher T cell ratios while A inhibitor patients had higher B cell ratios.  The explanation of this is complex, but the bottom line is that A and B inhibitors may arise through different pathways.

This could help explain some of the differences we see in inhibitor incidence and treatment.  B patients have a much lower incidence of inhibitor development, for instance, than do A patients.  

Bs tend to develop allergic reactions to factor IX, while allergic reactions of As to factor VIII are rare.  Immune tolerance induction (ITI) is a method to tolerize patients against their clotting factor.  It is fairly successful in As but often ineffective in Bs.  Hopefully, these findings will spur more research on inhibitors in hemophilia B.  [ISTH abstract OC 41.3]