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Selumetinib for Refractory Pulmonary and Gastrointestinal Bleeding in Noonan Syndrome.
Pediatrics ( IF 6.2 ) Pub Date : 2022-10-01 , DOI: 10.1542/peds.2022-056336
Abhishek Chakraborty 1 , Gary Beasley 1 , Hugo Martinez 1 , Rohith Jesudas 2 , Pilar Anton-Martin 1 , Georgios Christakopoulos 2 , Jennifer Kramer 1
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A 15-year-old-boy with Noonan syndrome and status post orthoptic heart transplant developed mixed mitral valve disease and underwent mechanical mitral valve replacement 6 months before presentation with acute respiratory distress. He developed massive pulmonary hemorrhage that required veno-venous extracorporeal membrane oxygenation (ECMO) support. He had a prolonged anticoagulation free ECMO course of 4 weeks, with ongoing recurrent pulmonary hemorrhage and underwent several rounds of coil embolization of aortopulmonary collaterals. ECMO course was complicated by significant nasopharyngeal bleeding that required embolization of the sphenopalatine artery. Shortly after decannulation, he developed massive gastrointestinal and peritoneal hemorrhage that was treated by embolization of the left gastric artery and a branch of the internal iliac artery. His bleeding was attributed to neo-angiogenesis. Initial treatment with propranolol was unsuccessful. Subsequent treatment with interferon α 2b demonstrated efficacy, but severe neutropenia required cessation of therapy. Because functional alterations of the rat sarcoma virus-mitogen activated protein kinase signaling pathway and protein tyrosine phosphatase nonreceptor type (PTPN11) mutations in Noonan syndrome are known to be associated with neo-angiogenesis, we used the mitogen-activated protein kinase inhibitor selumetinib as a gene-targeted therapy with the hope of controlling bleeding and inhibiting neo-angiogenesis. After initiation of selumetinib, bleeding stopped and allowed the patient to be discharged from the hospital on dipyridamole as antiplatelet prophylaxis for his mechanical mitral valve. He had no further bleeding episodes through 1 year after hospital discharge.

中文翻译:

Selumetinib 治疗 Noonan 综合征的难治性肺和胃肠道出血。

一名 15 岁男孩患有 Noonan 综合征并在矫正心脏移植后出现混合性二尖瓣疾病,并在出现急性呼吸窘迫前 6 个月接受了机械二尖瓣置换术。他出现大量肺出血,需要静脉-静脉体外膜肺氧合 (ECMO) 支持。他接受了长达 4 周的无抗凝 ECMO 疗程,持续复发性肺出血,并接受了几轮主动脉肺侧支弹簧圈栓塞术。ECMO过程因需要栓塞蝶腭动脉的明显鼻咽出血而复杂化。拔管后不久,他出现大量胃肠道和腹膜出血,通过栓塞胃左动脉和髂内动脉分支进行治疗。他的出血归因于新血管生成。普萘洛尔的初始治疗不成功。随后用干扰素 α 2b 治疗显示出疗效,但严重的中性粒细胞减少症需要停止治疗。由于已知 Noonan 综合征中大鼠肉瘤病毒-丝裂原活化蛋白激酶信号通路和蛋白酪氨酸磷酸酶非受体型 (PTPN11) 突变的功能改变与新血管生成有关,因此我们使用丝裂原活化蛋白激酶抑制剂 selumetinib 作为基因靶向治疗有望控制出血和抑制新血管生成。开始使用 selumetinib 后,出血停止并允许患者出院,并使用双嘧达莫作为机械二尖瓣的抗血小板预防。
更新日期:2022-09-09
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