Wolfgang Miesbach/LinkedIn
Feb 20, 2026, 17:35
Wolfgang Miesbach: Plasma FIX Is Only Part of the Story In Haemophilia B
Wolfgang Miesbach, Professor of Medicine at Frankfurt University Hospital, shared a post on LinkedIn:
“At EAHAD 2026 it became very clear that, in haemophilia B, plasma FIX is only part of the story.
Great presentation by Cedric Hermans.
- FIX ≠ FVIII
FVIII is mainly intravascular, while FIX distributes both intra‑ and extravascularly, binding to collagen IV and endothelium and forming a kind of tissue ‘reservoir’. This dual compartment may help explain why some patients do better clinically than their plasma levels would suggest. - EHL‑FIX: more than just longer half‑life
The three extended half‑life FIX products use different technologies (Fc‑fusion, albumin‑fusion, PEGylation), leading to distinct volumes of distribution, extravascular engagement and joint localisation on imaging. These differences translate into variable trough levels and bleed protection across phase 3 studies, suggesting that EHL‑FIX products are not interchangeable simply on dose interval. - Extravascular FIX as ‘savings account’
I liked the analogy of intravascular FIX as “daily expenses” and extravascular FIX as “savings”: what we measure in plasma is immediately available, but the tissue‑bound pool may provide crucial back‑up at bleeding sites, as supported by several preclinical models.
This raises interesting questions for the future:
- How should we factor extravascular FIX into target levels and PK‑guided prophylaxis?
- What does this mean for choosing between different EHL‑FIX platforms and for interpreting FIX levels after gene therapy?”
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