Factor IXa

Pathway · Haemophilia B APTT Vitamin K dep.

Factor IX is activated by factor XIa on the intrinsic route and by TF-VIIa through the Josso loop. With its cofactor VIIIa, calcium and phospholipid it forms the intrinsic tenase complex, which activates factor X far more efficiently than TF-VIIa can — the reason haemophilia bleeds even though the extrinsic pathway is intact.

Traced from the start

  1. Contact activation system (factor XII, prekallikrein, high-molecular-weight kininogen)Vitamin K cycle and gamma-carboxylation
  2. Factor IXa

Detail

Vitamin K dependent
Yes — its Gla domain binds Ca2+ and anionic phospholipid
Activated by
Factor XIa, and by the tissue factor-factor VIIa complex
Forms
Intrinsic tenase: IXa + VIIIa + Ca2+ + phospholipid, which activates factor X
Gene
F9 on Xq27 — X-linked recessive, so males are affected and females are usually carriers
Measured by
APTT and a factor IX activity assay; the APTT corrects on 50:50 mixing unless an inhibitor is present

When it goes wrong

Haemophilia B (Christmas disease) — X-linked recessive factor IX deficiency, about 1 in 30,000 male births

Clinically indistinguishable from haemophilia A: haemarthrosis of knees, ankles and elbows, muscle haematoma and delayed post-traumatic bleeding. Prolonged APTT with normal PT, platelet count and bleeding time; only a factor assay separates them. Treat with recombinant factor IX — desmopressin does not work

Severe (under 1% activity) versus mild (5-40%) disease

Severe disease bleeds spontaneously into joints from the time of crawling and progresses to haemophilic arthropathy; mild disease may only declare itself after surgery or dental extraction

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