Successful liver transplant from a hemophilia A donor with no development of hemophilia A in recipient.
factor VIII
factor VIII inhibitor
hemophilia A
hemostasis
liver transplant
Journal
Journal of thrombosis and haemostasis : JTH
ISSN: 1538-7836
Titre abrégé: J Thromb Haemost
Pays: England
ID NLM: 101170508
Informations de publication
Date de publication:
04 2020
04 2020
Historique:
revised:
23
01
2020
accepted:
26
01
2020
pubmed:
31
1
2020
medline:
15
5
2021
entrez:
31
1
2020
Statut:
ppublish
Résumé
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.
Sections du résumé
BACKGROUND
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.
OBJECTIVE AND METHOD
We did a case report and literature review of a liver transplant receipient fro ma hemohpila A donor.
RESULTS
The receipient of the liver from hemophilia A donor did not develop hemophilia post transplant and had normal factor VIII levels.
CONCLUSION
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.
Identifiants
pubmed: 31997485
doi: 10.1111/jth.14750
pii: S1538-7836(22)00294-X
doi:
Substances chimiques
Factor VIII
9001-27-8
Types de publication
Case Reports
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
853-856Informations de copyright
© 2020 International Society on Thrombosis and Haemostasis.
Références
F8 gene - Genetics Home Reference - NIH. https://ghr.nlm.nih.gov/gene/F8. Accessed July 21, 2019.
Arruda VR. The search for the origin of factor VIII synthesis and its impact on therapeutic strategies for hemophilia A. Haematologica. 2015;100(7):849-850.
Marchioro TL, Hougie C, Ragde H, Epstein RB, Thomas ED. Hemophilia: role of organ homografts. Science. 1969;163(3863):188-190.
Madeira CL, Layman ME, de Vera RE, et al. Extrahepatic factor VIII production in transplant recipient of hemophilia donor liver. Blood. 2009;113(21):5364-5365.
Hisatake G, Chen T-W, Renz JF, et al. Acquired hemophilia A after liver transplantation: a case report. Liver Transplant. 2003;9(5):523-526.
Groth CG, Hathaway WE, Gustafsson A, et al. Correction of coagulation in the hemophilic dog by transplantation of lymphatic tissue. Surgery. 1974;75(5):725-733.
Norman JC, Covelli VH, Sise HS. Transplantation of the spleen: experimental cure of hemophilia. Surgery. 1968;64(1):1-14.
Everett LA, Cleuren ACA, Khoriaty RN, Ginsburg D. Murine coagulation factor VIII is synthesized in endothelial cells. Blood. 2014;123(24):3697-3705.
Fahs SA, Hille MT, Shi Q, Weiler H, Montgomery RR. A conditional knockout mouse model reveals endothelial cells as the principal and possibly exclusive source of plasma factor VIII. Blood. 2014;123(24):3706-3713.
Shahani T, Covens K, Lavend'homme R, et al. Liver sinusoidal endothelial cells but not hepatocytes contain factor VIII. J Thromb Haemost. 2014;12(1):36-42.
Zanolini D, Merlin S, Feola M, et al. Extrahepatic sources of factor VIII potentially contribute to the coagulation cascade correcting the bleeding phenotype of mice with hemophilia A. Haematologica. 2015;100(7):881-892.