Pilot study to test the efficacy and safety of activated recombinant factor VII (NovoSeven) in the treatment of refractory hemorrhagic cystitis following high-dose chemotherapy.
Pilot study to test the efficacy and safety of activated recombinant factor VII (NovoSeven) in the treatment of refractory hemorrhagic cystitis following high-dose chemotherapy.
复制标题
测试活化重组因子 VII (NovoSeven) 治疗大剂量化疗后难治性出血性膀胱炎的有效性和安全性的初步研究。
DOI：
10.1038/sj.bmt.1705535
复制
发表时间：
2006
影响因子：
4.8
通讯作者：
Key,NS
中科院分区：
文献类型：
--
作者：
Ashrani,AA;Gabriel,DA;Gajewski,JL;JacobsJr,DR;Weisdorf,DJ;Key,NS
出血性膀胱炎(HC)是大剂量环磷酰胺化疗的已知并发症。1在接受干细胞移植(SCT)的患者中，约有5%发生严重的HC，可能导致尿路梗阻、急性肾功能衰竭、肾积水、膀胱穿孔和死亡。2慢性丙型肝炎患者的治疗效果往往不理想，主要是支持性措施。1大剂量活化重组因子VII(rFVIIa/NovoSeven，诺和诺德A/S，丹麦BagsvæRd)是一种被批准用于治疗血友病A或B患者使用抑制剂的出血事件的止血剂。RFVIIa已被评估为在各种其他出血情况下的促止血剂，3包括SCT中的出血。4-6我们报告了一项初步研究的结果，以测试rFVIIa在HC中的疗效。符合条件的受试者年龄在18至65岁之间，患有严重的HC(定义为有尿路凝块和耻骨上疼痛的无控制血尿，既往接触环磷酰胺或异环磷酰胺，没有尿路感染的证据)，他们对(I)优化止血参数和(Ii)连续膀胱冲洗(CBI)至少24小时的试验没有反应。如果患者有(A)明显的弥散性血管内凝血(DIC)；(B)过去3个月内心肌梗死或不稳定型心绞痛；(C)最近中风；(D)最近中心静脉通路装置相关的血栓；(E)肝静脉闭塞疾病；(F)自发性深静脉血栓形成史；(G)过去7天内血培养阳性；(H)对rFVIIa过敏反应；(I)怀孕；(J)在过去24小时内应用局部或全身抗纤溶药物；或(K)同时应用粒细胞-巨噬细胞集落刺激因子或大剂量雌激素治疗。RFVIIa在5-120mcg/kg的剂量范围内已用于各种出血情况的治疗，消除半衰期约为3h。3因此，如果血尿持续存在，我们选择先静脉注射80mcg/kg，然后再静脉注射rFVIIa 120mcg/kg，间隔3h最多两次。所有受试者继续标准的重力驱动高流量脑血流显像。受试者可以在第一次注射rFVIIa前1h和之后9h接受血小板输注，但不能在过渡期间接受。用照相方法评价rFVIIa的疗效。
Hemorrhagic cystitis (HC) is a known complication of high-dose cyclophosphamide chemotherapy. 1 Approximately 5% of patients undergoing stem cell transplantation (SCT) develop severe HC, which may lead to urinary obstruction, acute renal failure, hydronephrosis, bladder perforation and death. 2 Treatment of patients with HC is frequently unsatisfactory, and mainly consists of supportive measures. 1High-dose activated recombinant factor VII (rFVIIa/NovoSeven, NovoNordisk A/S, Bagsværd, Denmark) is a hemostatic agent approved for the treatment of bleeding episodes in hemophilia A or B patients with inhibitors. rFVIIa has been evaluated as a pro-hemostatic agent in a variety of other hemorrhagic conditions, 3 including hemorrhage in the setting of SCT. 4–6 We report the result of a pilot study to test the efficacy of rFVIIa in HC. Eligible study subjects were between 18 and 65 years of age with severe HC (defined as uncontrolled hematuria with urinary clots and suprapubic pain, with prior exposure to cyclophosphamide or ifosfamide, and without evidence of urinary tract infection), who were unresponsive to (i) optimization of hemostatic parameters and (ii) a trial of at least 24h of continuous bladder irrigation (CBI). Patients were excluded if they had (a) overt disseminated intravascular coagulation (DIC);(b) myocardial infarction within the previous 3 months, or unstable angina;(c) recent stroke;(d) recent central venous access device-related thrombus;(e) hepatic veno-occlusive disease;(f) history of spontaneous deep vein thrombosis;(g) positive blood culture within the last 7 days;(h) allergic reaction to rFVIIa;(i) pregnancy;(j) topical or systemic antifibrinolytic agents administered in the last 24h or (k) concurrent granulocyte–macrophage colony-stimulating factor or high-dose estrogen therapy. rFVIIa in the dose range of 5–120mcg/kg has been employed in the management of various hemorrhagic conditions and has an elimination half-life of about 3h. 3 Therefore, we elected to administer an initial dose of 80mcg/kg intravenously (iv) followed by up to two additional doses of rFVIIa 120mcg/kg iv administered 3h apart, if hematuria persisted. All subjects continued standardized gravity-driven high flow CBI. Subjects could receive platelet transfusion 1 h before, and 9 h following the first dose of rFVIIa, but not during the interim. The efficacy of rFVIIa was evaluated by photographically