Kawasaki Yuki, Nakajima Yuto, Nogami Keiji
Department of Pediatrics, Nara Medical University, Kashihara, Nara, Japan.
Haemophilia. 2025 Jul 8. doi: 10.1111/hae.70087.
Steady-state plasma concentrations of emicizumab in people with haemophilia A (PwHA) range from approximately 30 to 50 µg/mL, although some PwHA treated effectively with low doses of emicizumab have been reported. Little information is available, however, on the coagulation potential of bypassing agents (BPAs) under low concentration of emicizumab.
To assess the coagulation potential of BPAs in PwHA plasma at low concentration of emicizumab.
In FVIII-deficient plasmas spiked with emicizumab (2.5-10 µg/mL), concomitant effects of FVIII (1.0 IU/mL) or BPAs (recombinant (r)FVIIa; corresponding to 90 and 180 µg/kg, activated prothrombin complex concentrates (aPCC); 50 and 100 IU/kg, plasma-derived FVIIa/FX (pd-FVIIa/FX); 60 and 120 µg/kg) were assessed by tissue factor-triggered thrombin generation assay. In 10 emicizumab-treated PwHA plasmas on the loading and maintenance phases (mean plasma emicizumab concentration; 15 ± 2 and 50 ± 4 µg/mL, respectively), coagulation potential in them spiked with BPAs (rFVIIa 90, 270 µg/kg, aPCC 50 IU/kg and pd-FVIIa/FX 60 µg/kg) was monitored.
The Peak thrombin (PeakTh) in FVIII-deficient plasma spiked with emicizumab (2.5-10 µg/mL) and FVIII was comparable to that spiked with FVIII alone, and that spiked with emicizumab and BPA were mildly to evidently greater than that spiked with BPA alone. In emicizumab-treated PwHA plasmas, the aPCC or pd-FVIIa/FX increased coagulation potentials. The rFVIIa (90 µg/kg) did not enhance coagulation potentials on the loading phase but improved them on the maintenance phase. The rFVIIa (270 µg/kg) enhanced coagulation potentials on the loading phase.
We should adjust BPA dosage in PwHA under low concentration of emicizumab.
A型血友病患者（PwHA）中emicizumab的稳态血浆浓度范围约为30至50μg/mL，不过有报道称一些低剂量emicizumab治疗有效的PwHA。然而，关于低浓度emicizumab下旁路剂（BPA）的凝血潜力的信息很少。
评估低浓度emicizumab时PwHA血浆中BPA的凝血潜力。
在添加emicizumab（2.5 - 10μg/mL）的FVIII缺陷血浆中，通过组织因子触发的凝血酶生成试验评估FVIII（1.0 IU/mL）或BPA（重组（r）FVIIa；分别对应90和180μg/kg，活化凝血酶原复合物浓缩物（aPCC）；50和100 IU/kg，血浆源性FVIIa/FX（pd - FVIIa/FX）；60和120μg/kg）的协同作用。在10例处于负荷期和维持期的emicizumab治疗的PwHA血浆中（平均血浆emicizumab浓度分别为15±2和50±4μg/mL），监测添加BPA（rFVIIa 90、270μg/kg，aPCC 50 IU/kg和pd - FVIIa/FX 60μg/kg）后的凝血潜力。
添加emicizumab（2.5 - 10μg/mL）和FVIII的FVIII缺陷血浆中的凝血酶峰值（PeakTh）与仅添加FVIII的相当，添加emicizumab和BPA的明显高于仅添加BPA的。在emicizumab治疗的PwHA血浆中，aPCC或pd - FVIIa/FX增加了凝血潜力。rFVIIa（90μg/kg）在负荷期未增强凝血潜力，但在维持期有所改善。rFVIIa（270μg/kg）在负荷期增强了凝血潜力。
在低浓度emicizumab的PwHA中，我们应调整BPA剂量。
