Department of Pediatrics, Nara Medical University, Kashihara, Nara, Japan.
The Course of Thrombosis and Hemostasis Molecular Pathology, Nara Medical University, Nara, Japan.
Pediatr Blood Cancer. 2022 Jul;69(7):e29731. doi: 10.1002/pbc.29731. Epub 2022 Apr 20.
Emicizumab prophylaxis reduces bleeding in hemophilia A (HA) patients. However, there are few data on emicizumab treatment in neonates with HA (neonate-HA), and the procoagulant effects of emicizumab in these patients are unknown.
To investigate the coagulation activity of emicizumab in vitro in a plasma model of neonate-HA.
Plasmas from 84 neonates with non-HA were enrolled. However, due to the limited plasma volumes in some cases, 50 plasmas were assigned to two different assay groups. To prepare the neonate-HA model, plasma was first preincubated with an antifactor (F) VIII A2 monoclonal antibody (mAb). After further incubation with emicizumab, global coagulation activity was measured: adjusted maximum coagulation velocity (Ad|min1|) in clot waveform analysis (CWA) and peak thrombin in thrombin generation assay (TGA).
Because the addition of anti-FVIII mAb to 22 of 43 samples showed little decrease in Ad|min1|, the remaining 21 samples were analyzed by CWA. The addition of emicizumab increased Ad|min1| in 18 of the 19 cases (effective group) but not in the remaining 3 cases (noneffective group). Similarly, TGA found that emicizumab (effective group) improved peak thrombin in seven of the nine samples tested, but two cases did not respond (noneffective group). Although the effective group had lower levels of FX, there was no significant difference between the effective and noneffective groups in terms of FIX, protein S, protein C, antithrombin, and fibrinogen.
The in vitro coagulant potentials of emicizumab in the neonate-HA model were more heterogeneous than those recorded in the adult-HA model.
依库珠单抗预防治疗可减少 A 型血友病（HA）患者的出血。然而，目前关于新生儿 HA（neonate-HA）患者接受依库珠单抗治疗的数据较少，并且尚不清楚依库珠单抗在这些患者中的促凝作用。
在 neonate-HA 的血浆模型中体外研究依库珠单抗的凝血活性。
纳入 84 例非 HA 新生儿的血浆。然而，由于某些情况下血浆量有限，将 50 份血浆分配到两个不同的检测组。为制备 neonate-HA 模型，首先将血浆与抗因子（F）VIII A2 单克隆抗体（mAb）预孵育。在进一步与依库珠单抗孵育后，测量整体凝血活性：在凝血波型分析（CWA）中调整的最大凝血速度（Ad|min1|）和在凝血酶生成试验（TGA）中的峰值凝血酶。
由于向 43 份样本中的 22 份添加抗 FVIII mAb 后 Ad|min1| 减少甚微，因此对其余 21 份样本进行 CWA 分析。添加依库珠单抗增加了 19 例中的 18 例（有效组）的 Ad|min1|，但在其余 3 例（无效组）中未增加。同样，TGA 发现依库珠单抗（有效组）改善了 9 份测试样本中的 7 份峰值凝血酶，但 2 份样本无反应（无效组）。尽管有效组的 FX 水平较低，但有效组和无效组在 FIX、蛋白 S、蛋白 C、抗凝血酶和纤维蛋白原方面没有显著差异。
依库珠单抗在 neonate-HA 模型中的促凝血潜能比在成人 HA 模型中更为复杂。
