Lack of desmopressin (DDAVP) response in men with hemophilia A following liver transplantation
Lack of desmopressin (DDAVP) response in men with hemophilia A following liver transplantation
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DOI：
10.1111/j.1538-7836.2005.01553.x
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发表时间：
2005-10-01
影响因子：
10.4
通讯作者：
Ragni, MV
中科院分区：
文献类型：
--
作者：
Lamont, PA;Ragni, MV
虽然血友病A是一种由因子VIII：C(FVIII)缺陷或缺陷引起的先天性疾病，可通过肝移植治愈，但肝脏产生FVIII的确切位置尚不清楚。此外，虽然体外分泌FVIII需要FVIII和von Willebrand因子(VWF)的细胞内共定位，但是否需要体内FVIII分泌尚不清楚。研究这一问题的理想环境是肝移植后患有血友病A的患者，因为他们的FVIII主要在肝脏内皮细胞合成，而不是在肝外血管内皮细胞中合成，而VWF主要在肝外血管内皮细胞合成。在终末期肝病的肝移植后，三名血友病患者出现了VWF，但对输注(DDAVP)没有FVIII反应。相比之下，非血友病移植受者DDAVP后VWF和FVIII均升高。这些发现支持一种模型，在该模型中，对于DDAVP后体内FVIII的分泌来说，FVIII和VWF的细胞内共同定位是必要的。
Although hemophilia A, a congenital disorder caused by defective or deficient factor VIII:C (FVIII), is cured by liver transplantation, the exact site of hepatic FVIII production is unknown. Further, while intracellular co-localization of FVIII and von Willebrand factor (VWF) is required for in vitro FVIII secretion, whether it is required for in vivo FVIII secretion is not known. An ideal setting to study this problem is in individuals with hemophilia A following liver transplantation, as their FVIII is synthesized primarily in hepatic, but not extrahepatic endothelial cells, while VWF is synthesized primarily in extrahepatic vascular endothelium. Following liver transplantation for end-stage liver disease, three hemophilic men showed VWF, but no FVIII response to (DDAVP) infusion. By contrast, both VWF and FVIII increased in a non-hemophilic transplant recipient after DDAVP. These findings support a model in which intracellular co-localization of FVIII and VWF is necessary for in vivo FVIII secretion after DDAVP.