Skip to content

How do you prescribe and monitor antithrombin inhibitor therapy?

Current as of 20 October 2026 · added 20 October 2026

Answer: Fitusiran (siRNA) lowers antithrombin levels. It is approved in the USA for bleeding prophylaxis in people with hemophilia A or B, with or without inhibitors.

  • Dosing: 50 mg every 2 months, to target antithrombin activity of 15–35%. Levels are checked at months 1, 3, 5, and 6, with adjustments made to maintain that level; lower the dose if <15%. The drug has a 6-month washout.
  • Switching to fitusiran:

When changing from other products to fitusiran, the half-life of the previous product should be considered to ensure complete wash-out. For example:12 hours for recombinant FVIIa (rFVIIa), 48 hours for activated prothrombin complex concentrate (aPCC), 24 hours for standard half-life (SHL) factor VIII (FVIII) or factor IX (FIX) product. There is no data on changing from FVIII mimetic therapy or anti tissue factor inhibitor therapy to fitusiran. The complete washout period for emicizumab is six months.

  • Treatment of breakthrough bleeding: dosing is significantly lower (MASAC table below). Real-world evidence is extremely limited; for surgical management, even less so.

    Agent Recommended dose Repeat dosing
    Factor VIII 10 IU/kg (max: 20 IU/kg) Should not repeat in < 24 hours
    Factor IX (SHL) 20 IU/kg (max: 30 IU/kg) Should not repeat in < 24 hours
    Factor IX (EHL) 20 IU/kg (max: 30 IU/kg) Should not repeat in < 5 to 7 days
    aPCC 30 IU/kg (max: 50 IU/kg) Should not repeat in < 24 hours
    rFVIIa < 45 micrograms/kg Should not repeat in < 2 hours

  • Adverse effects:

    1. Black box warning for thromboembolic events: 2.6% on the 80 mg once-monthly dose (not approved), vs 1.4% on the approved antithrombin-based dosing regimen.
    2. Counsel on gallbladder disease and hepatotoxicity: cholelithiasis and cholecystitis in 17% on the non-approved fixed-dose regimen, with 4% requiring cholecystectomy (3.8% gallbladder events on the approved regimen).
    3. Not recommended in hepatic impairment (Child-Pugh A–C).

Source: MASAC Document 295 — Recommendation on the Use and Management of Antithrombin Inhibitor