Onishi Tomoko, Harada Suguru, Shimo Hanako, Tashiro Yoshihito, Soeda Tetsuhiro, Nogami Keiji
Department of Pediatrics, Nara Medical University, Kashihara, Nara, Japan.
Chugai Pharmaceutical Co., Ltd., Yokohama, Kanagawa, Japan.
Haemophilia. 2023 Nov;29(6):1529-1538. doi: 10.1111/hae.14877. Epub 2023 Sep 27.
Emicizumab is used as hemostatic prophylaxis for patients with hemophilia A (PwHA), irrespective of the presence of inhibitors. Although bacterial infection can lead to a procoagulant state, there is limited information on coagulation and fibrinolysis potentials in emicizumab-treated PwHA and on the use of anticoagulants in such cases.
We examined whether anticoagulants affect the coagulation and fibrinolysis potentials in plasma from PwHA spiked with emicizumab.
Plasma from PwHA was in vitro supplemented with emicizumab (50 μg/mL; emi-plasma) and anticoagulants (recombinant thrombomodulin (rTM), nafamostat mesylate (NM), unfractionated heparin (UFH), or low-molecular-weight heparin (LMH)). PwHA plasma spiked with rFVIII (1 IU/mL) was used as a reference (ref-plasma). The coagulation and fibrinolysis potentials in plasma was measured by thrombin and plasmin generation assay (T/P-GA) and clot-fibrinolysis waveform analysis (CFWA).
In T/P-GA and CFWA, coagulation potentials (maximum coagulation velocity; |min1|, and peak thrombin; Th-Peak) in plasma rose with increasing concentrations of emicizumab and rFVIII, but fibrinolytic potentials (peak plasmin; Plm-Peak, and maximum fibrinolytic velocity; |FL-min1|) remained unchanged. Adding rTM, NM, and UFH to emi-plasma suppressed coagulation and fibrinolysis potentials, similar to ref-plasma. Regarding the heparin, UFH and LMH inhibited the improved coagulation in emi-plasma. UFH inhibited fibrinolysis as well, but LMH did not.
Anticoagulants could exhibit the inhibitory effects on the coagulation and fibrinolysis potentials in plasma from PwHA spiked with emicizumab, similar to those in normal plasma.
无论是否存在抑制剂，艾美赛珠单抗均用于血友病A患者（PwHA）的止血预防。尽管细菌感染可导致促凝状态，但关于接受艾美赛珠单抗治疗的PwHA的凝血和纤维蛋白溶解潜能以及此类情况下抗凝剂的使用信息有限。
我们研究了抗凝剂是否会影响添加了艾美赛珠单抗的PwHA血浆中的凝血和纤维蛋白溶解潜能。
在PwHA血浆中体外添加艾美赛珠单抗（50μg/mL；艾美血浆）和抗凝剂（重组血栓调节蛋白（rTM）、甲磺酸萘莫司他（NM）、普通肝素（UFH）或低分子肝素（LMH））。添加了rFVIII（1IU/mL）的PwHA血浆用作对照（对照血浆）。通过凝血酶和纤溶酶生成试验（T/P-GA）和凝块纤维蛋白溶解波形分析（CFWA）测量血浆中的凝血和纤维蛋白溶解潜能。
在T/P-GA和CFWA中，血浆中的凝血潜能（最大凝血速度；|min1|，和凝血酶峰值；Th-Peak）随着艾美赛珠单抗和rFVIII浓度的增加而升高，但纤维蛋白溶解潜能（纤溶酶峰值；Plm-Peak，和最大纤维蛋白溶解速度；|FL-min1|）保持不变。向艾美血浆中添加rTM、NM和UFH可抑制凝血和纤维蛋白溶解潜能，类似于对照血浆。关于肝素，UFH和LMH抑制了艾美血浆中改善的凝血。UFH也抑制纤维蛋白溶解，但LMH没有。
抗凝剂可能对添加了艾美赛珠单抗的PwHA血浆中的凝血和纤维蛋白溶解潜能表现出抑制作用，类似于正常血浆中的作用。
