Timothy Craig is a doctor of orthopedics and a leading clinical researcher in the field of allergy and immunology. He describes the role that factor XII has in each type of hereditary angioedema.

Factor XII being at the very top of the cascade is very important. Some people actually genetically have absent factor XII and they can live a normal life. 

And once you inhibit factor XII, you kind of inhibit that whole cascade leading to the production of bradykinin and those changes that lead to swelling and edema in people who have hereditary angioedema. 

Now there is a different type of the hereditary angioedema with normal C1 inhibitor that actually has a gain of function factor XII. That is, that factor XII is amplified and it leads to increased production of bradykinin. 

So again, in type 1 and type 2, there’s a lack of C1 inhibitor and because of that, factor XII can be easily activated and then activate the rest of the pathway. 

Then there’s those people who fall into HAE with normal C1 inhibitor and one group of those individuals actually have a gain of function of factor XII that leads to the increased bradykinin. 

Now those people fortunately respond very similar to type 1 and type 2 to the medications that are available.