Kurian Christine J, Drelich Douglass A, Rizk Sanaa
Cardeza Foundation for Hematologic Research, Department of Medicine, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA.
J Thromb Haemost. 2020 Apr;18(4):853-856. doi: 10.1111/jth.14750. Epub 2020 Mar 9.
Hemophilia A is an X-linked inherited bleeding disorder caused by deficiency of coagulation factor VIII. Factor VIII is activated as part of the intrinsic coagulation cascade. It plays a crucial role as the cofactor in the intrinsic "tenase" complex activating factor X to assist in clot formation. Absence or mutation of this coagulation factor leads to excessive bleeding. Clinical manifestations of hemophilia relate to bleeding from impaired hemostasis, sequelae from bleeding, or complications of coagulation factor infusion. Diagnostic criteria for Hemophilia A include factor VIII activity level below 40% of normal, presence of a mutated F8 gene, and the absence of von Willebrand disease (F8 gene - Genetics Home Reference - NIH. https://ghr.nlm.nih.gov/gene/F8). Patients who have this intrinsic defect in the coagulation cascade have a characteristically prolonged PTT. It is theorized that the majority of factor VIII is synthesized mainly in the liver, by way of liver sinusoidal endothelial cells (Arruda VR. Haematologica. 2015;100(7):849-850). Extrahepatic production also occurs in the endothelial cells, kidneys, and lymphatic tissue. In 1969, Marchioro et al showed that transplantation of normal liver to hemophilia dog could normalize plasma factor VIII levels (Marchioro T L, Science. 1969;163(3863):188-190). These results were subsequently proven in humans. Liver transplantation from hemophilia A donors without factor VIII inhibitor is not commonly performed due to the perceived risk of developing hemophilia A in the recipient. There is currently limited literature aimed at elucidating this risk. We present a case of liver transplantation in a hemophilia A donor to a recipient with no history of hemophilia A with literature reviewis a case report, objective and method do not apply.
We did a case report and literature review of a liver transplant receipient fro ma hemohpila A donor.
The receipient of the liver from hemophilia A donor did not develop hemophilia post transplant and had normal factor VIII levels.
To our knowledge, this is only the second case in humans of hemophilia A patient as a donor in liver transplantation. As the indications for liver transplantation have expanded, there is a need to expand the donor list, and possibly not exclude this population as viable donor option.
甲型血友病是一种X连锁遗传性出血性疾病，由凝血因子VIII缺乏引起。凝血因子VIII作为内源性凝血级联反应的一部分被激活。它作为内源性“凝血酶原酶”复合物中的辅因子，在激活因子X以协助凝血形成过程中发挥关键作用。这种凝血因子的缺失或突变会导致出血过多。血友病的临床表现与止血功能受损引起的出血、出血后遗症或凝血因子输注并发症有关。甲型血友病的诊断标准包括因子VIII活性水平低于正常水平的40%、存在F8基因突变以及不存在血管性血友病（F8基因 - 遗传学家庭参考 - 美国国立医学图书馆。https://ghr.nlm.nih.gov/gene/F8）。在凝血级联反应中存在这种内在缺陷的患者，其部分凝血活酶时间（PTT）通常会延长。理论上，大多数因子VIII主要由肝脏通过肝窦内皮细胞合成（阿鲁达·VR。血液学。2015；100(7):849 - 850）。肝外合成也发生在内皮细胞、肾脏和淋巴组织中。1969年，马尔基奥罗等人表明，将正常肝脏移植到血友病犬体内可使血浆因子VIII水平正常化（马尔基奥罗·TL，科学。1969；163(3863):188 - 190）。这些结果随后在人类身上得到证实。由于认为受者有患甲型血友病的风险，所以通常不进行来自无因子VIII抑制剂的甲型血友病供体的肝脏移植。目前旨在阐明这种风险的文献有限。我们报告一例甲型血友病供体肝脏移植给无甲型血友病病史受者的病例，并进行文献复习（这是一篇病例报告，目标和方法不适用）。
我们报告一例接受甲型血友病供体肝脏移植受者的病例并进行文献复习。
接受甲型血友病供体肝脏移植的受者移植后未患血友病，且因子VIII水平正常。
据我们所知，这是人类中第二例甲型血友病患者作为肝脏移植供体的病例。随着肝脏移植适应症的扩大，有必要扩大供体名单，并且可能不应将这一人群排除在可行的供体选择之外。
