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Abstract：
Background Guidelines surrounding emicizumab prophylaxis and perioperative treatment for people with hemophilia A (PwHA) with factor (F)VIII inhibitors undergoing surgeries are limited. The phase IIIb multicenter, single-arm STASEY study evaluated safety and tolerability of emicizumab prophylaxis in PwHA aged ≥12 years with FVIII inhibitors. This analysis assesses surgeries during study conduct, associated hemophilia medications, and postoperative bleeds (treated and untreated). Methods PwHA with FVIII inhibitors received emicizumab 3.0 mg/kg/week for 4 weeks, then 1.5 mg/kg/week until 2 years. Surgeries were managed and documented by treating physicians. Bleeds and treatments were recorded by physicians and participants. Results Forty-six participants had ≥1 on-study surgery, 37 underwent 56 minor surgeries, and 13 underwent 22 major surgeries. Four participants underwent both minor and major surgeries. Of 18 (81.8%) and 4 (18.2%) major surgeries managed with/without additional hemostatic medication, 33.3 and 25.0% were associated with a treated postoperative bleed, respectively. Of 24 (42.9%) and 32 (57.1%) minor surgeries managed with/without additional hemostatic medication, 15.6 and 25.0% were associated with a treated postoperative bleed, respectively. Recombinant activated FVII was the most common medication for prophylaxis and bleed treatment. There were no thrombotic microangiopathies (TMAs). One hypertrophic clot, considered unrelated to emicizumab, occurred following tooth extraction. Conclusion In this challenging population with a high bleeding risk, major surgeries were performed in PwHA receiving emicizumab with/without additional hemostatic medication. Postoperative bleeds occurred following 59.1% of major surgeries; 53.8% were treated. No arterial/venous thrombotic events or TMAs occurred due to concomitant emicizumab and bypassing agents. Trial registration This trial is registered at ClinicalTrials.gov (NCT03191799).
摘要：
背景：对于接受手术治疗的血友病A（PwHA）患者使用因子（F）VIII抑制剂的患者，围绕埃米珠单抗预防和围手术期治疗的指南是有限的。IIIb多中心阶段，单臂STASEY研究评估了使用FVIII抑制剂的年龄≥12岁的PwHA患者使用emicizumab预防的安全性和耐受性.本分析评估研究期间的手术，相关的血友病药物，和术后出血（治疗和未治疗）。方法使用FVIII抑制剂的PwHA接受美珠单抗3.0mg/kg/周治疗4周,然后1.5毫克/公斤/周，直到2年。手术由治疗医生管理和记录。医生和参与者记录了出血和治疗。结果46名参与者进行了≥1次研究手术，37人接受了56次小手术，13人接受了22次重大手术。四名参与者接受了小型和大型手术。在18例（81.8%）和4例（18.2%）大手术中有/没有额外的止血药物，33.3%和25.0%与治疗后出血相关，分别。在24例（42.9%）和32例（57.1%）小手术中有/没有额外的止血药物，15.6%和25.0%与治疗后出血相关，分别。重组活化FVII是最常用的预防和出血治疗药物。没有血栓性微血管病（TMAs）。一个肥大的血块,被认为与emicizumab无关，发生在拔牙后。结论在这个具有高出血风险的挑战性人群中，在接受有/没有额外止血药物的emicizumab的PwHA中进行了主要手术.59.1％的大型手术后发生术后出血；53.8％得到治疗。没有因伴随的emicizumab和旁路剂而发生动脉/静脉血栓事件或TMA。试验注册本试验在ClinicalTrials.gov(NCT03191799)注册。
