Initiating treatment with emicizumab in the neonatal period may benefit patients with hemophilia A, according to a new study published in Pediatric Blood & Cancer.

The experimental study conducted by Takeyama and colleagues analyzed plasma from 21 healthy neonates and created a hemophilia model by adding an anti-factor (F) VIII A2 monoclonal antibody (mAb) to observe the in vitro coagulant properties prior to and after administering emicizumab.

The samples were classified into the “effective” group whenever the adjusted maximum coagulation velocity (Ad|min1|) or peak thrombin increased above the coefficient variation after the addition of emicizumab. Samples that did not meet the criteria formed the “noneffective” group.


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Clot waveform analysis reported an increased Ad|min1| in all 7 samples after an emicizumab dose of 100 μg/mL, whereas only 11 out of 14 had the same result with 50 μg/mL. Moreover, thrombin generation assays showed higher peak thrombin in most of the samples, 7 in the effective group and 2 in the noneffective group.

Finally, the authors studied the differences between the effective and noneffective groups, observing that the latter had higher levels of FX but similar FIX, protein S, protein C, antithrombin, and fibrinogen levels.

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These results demonstrated a more heterogeneous success among the blood samples of neonates when comparing them to results from prior publications that analyzed the coagulation properties in adult hemophilia models. This suggests that initiating treatment with emicizumab as early as the neonatal period may bring added benefits to patients with this disease.

“The Ad|min1| results of the early infant-[hemophilia A] model were decreased after the addition of an anti-FVIII mAb and were increased by the subsequent addition of emicizumab,” the authors said. “These initial findings in the early infant-[hemophilia A] model appeared to be more consistent than in the corresponding neonate-[hemophilia A] model and were similar to those observed in the adult-[hemophilia A] model.”

“These effects of age remain to be fully investigated, but it may be that emicizumab could be optimally effective at an age when coagulant and anticoagulant reactions become close to the reference values in adults.”

Regardless of yielding valuable information, this study’s greatest limitation is the dependence on the in vitro simulation of neonatal hemophilia A. Blood from neonates with this disease should be analyzed under similar parameters to later conduct in vivo trials to validate the results further.

Reference

Takeyama M, Furukawa S, Onishi T, Noguchi-Sasaki M, Shima M, Nogami K. Heterogeneous coagulant potential of emicizumab in neonatal factor VIII–deficient plasma. Pediatr Blood Cancer. Published online April 20, 2022. doi:10.1002/pbc.29731