The combination of activated factor VII and factor X (FVIIa/FX) can work as an effective bypass hemostatic therapy with a low risk of overcoagulation in patients with hemophilia with inhibitors and low FX levels, according to a study published in Thrombosis Update.

The study assessed thrombin generation (TG) and activated partial thromboplastin time (aPTT) in vitro under low and high FX concentrations.

When plasma-derived FX (pdFX) concentrations ranging from 0 IU/mL to 1.28 IU/mL were added to models of hemophilia A and B plasma with inhibitors in the presence of recombinant FVIIa, TG exhibited changes in a pdFX concentration-dependent manner. The highest pdFX concentration of 1.28 IU/mL resulted in a peak TG height similar to that in normal plasma.


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When FX concentrations were low, the addition of higher levels of FVIIa did not fully restore TG to normal levels. The introduction of additional FVIIa/FX (62.5/2 IU/mL) did normalize TG, however. The addition of FVIIa/FX resulted in stable TG and aPTT independent of low FX concentrations (0.13-0.64 IU/mL).

“Simultaneous FX supplementation in addition to FVIIa may be effective in promoting hemostasis under low plasma FX levels,” the authors said.

TG and aPTT were evaluated at initial FX concentrations ranging from 0 to 20 IU/mL to assess the possibility of overcoagulation in the event that FX levels become too high due to the frequent usage of a combination FVIIa/FX product. The TG peak height after the administration of FVIIa/FX was found to be dependent on the initial FX concentration up to 10 IU/mL, but it was not significantly different between initial concentrations of 12 and 20 IU/mL.

Increased FX levels also shortened aPTT with the addition of FVIIa/FX, with times of 51.8 seconds, 30.9 seconds, and 27.5 seconds at FX concentrations of 0 IU/mL, 4 IU/mL, and 8 IU/mL, respectively. The aPTT was not significantly different at FX concentrations between 4 and 20 IU/mL, however, the mean aPTT was at or below the normal plasma time of 32.5 seconds.

Reference

Miyashita R, Shinozawa K, Takami E, Ohkuma K, Amano K. Effects of low and high factor X concentrations on thrombin generation in vitro. Thrombosis Update. 2022;8:100111. doi:10.1016/j.tru.2022.100111