Impact of Natural Variation in Clotting Factor Levels on Bleeding in Hemophilia

By Dr. David Clark 

12/7/24 

Why do two hemophilia patients with the same factor levels bleed differently?  That’s one of the big questions in hemophilia.  One possibility is that the levels of other clotting factors and anticoagulants vary from person to person.  We’ve seen from the work on rebalancing agents that varying the levels of anticoagulants can have a significant effect on clotting behavior.  The same is probably true of the levels of the other clotting factors.  At ASH, a group from the University of North Carolina explored that question. 

In laboratory experiments with donated plasma, the researchers varied the levels of a number of clotting factors and inhibitors and found that indeed, the levels of many of those components significantly affected clotting times.  They found that factors VIII and IX had the strongest correlation between clotting time and factor level, as might be expected since their absence causes hemophilia.  Factor XII was next followed by factor XI, two clotting factors we don’t talk about much.  Factors XI and XII work near the beginning of the pathway that ends with factors VIII and IX activating factor X.  They also found that levels of C1 esterase inhibitor, an inhibitor of both factors XI and XII had a significant effect, as would be expected.  [ASH abstract 1202]