Successful liver transplant from a hemophilia A donor with no development of hemophilia A in recipient

Kurian, Christine; Drelich, Douglass A.; Rizk, Sanaa

doi:10.1111/jth.14750

Cited by 5 publications

(5 citation statements)

References 10 publications

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“…Their studies showed that liver sinusoidal endothelial cells and extrahepatic cells (including the lung, spleen, kidney, brain, intestine, and tongue) did not express factor IX mRNA. In comparison, factor VIII is produced extrahepatically, and transplant of a liver from a donor carrying the diagnosis of hemophilia A did not lead to development of the bleeding disorder in the recipient [12][13][14][15].…”

Section: Discussionmentioning

confidence: 98%

Acquired Hemophilia B Through Liver Transplantation: A Case Report and Literature Review

Kurian¹,

Drelich²,

Rizk³

2020

AJIM

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Hemophilia B, also called Christmas disease, is an X-linked inherited bleeding disorder that predominantly affects males, and it is caused by deficiency of coagulation factor IX. Factor IX is a coagulation factor produced in the liver. Liver transplantation from hemophilia B donors is neither widely documented nor performed due to presumed risk of developing increased bleeding tendency in the recipient due to potential acquired factor IX deficiency. In this review, we present a case of liver and kidney transplantation from a donor with mild hemophilia B to a recipient with no history of hemophilia B and literature review. This is a relatively rare situation with only two other prior case reports of acquired Hemophilia B through liver transplantation noted in 2015. The 2 cases presented in the literature lead to acquired hemophilia B in liver transplant recipients since donors were not screened due to mild disease and low suspicion level. In our case, the donor was known to have mild Hemophilia B and the recipient had a rapid decline -thus it is imperative to weigh risks and benefits of transplantation from this donor population. While those individuals with mild hemophilia B disease (and low bleeding burden) should be considered as an alternative donor for liver transplantation, appropriate counseling should be done with the recipient about possible bleeding risks and OLT should only occur after patient consent. A multidisciplinary approach should involve hematology in case factor replacement therapy is needed post transplantation and for long term follow up.

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Section: Discussionmentioning

confidence: 98%

Acquired Hemophilia B Through Liver Transplantation: A Case Report and Literature Review

Kurian¹,

Drelich²,

Rizk³

2020

AJIM

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“…However, the opposite is also true and several case reports describe the transmission of hemophilia through OLT, with phenotypes ranging from mild to severe in the recipient postoperatively (Table 3). [25][26][27][28][29][30][31][32] While numerous case reports indicate that hemophilia A donors can transmit the disorder to the transplant recipient, most recipients have mild disease due to extrahepatic synthesis of factor VIII in the recipient (Table 3).…”

Section: Hemophiliamentioning

confidence: 99%

“…No bleeding complications Normal factor VIII levels (likely due to extrahepatic production) Post-op elevated aPTT, PT attributed to heparin therapy, vitamin K deficiency Hemophilia A Kurian et al [26] No genotype testing found on the chart Hemophilia B Brunetta et al [28] Undiagnosed at the time of donation No diagnosis of bleeding disorder. In retrospect, had a history of large thigh hematomas after injury.…”

Section: Von Willebrand Diseasementioning

confidence: 99%

Donor-derived disorders of hemostasis and thrombosis in liver transplantation: Considerations for deceased donor liver selection

Atthota

Macdonald

Markmann

et al. 2023

Liver Transplantation

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Orthotopic liver transplantation (OLT) is known to be associated with a precarious perioperative hemostatic state due to dysregulation of procoagulant and anticoagulant factors, endothelial injury, and inflammation. Transmission of inherited bleeding and clotting disorders from the liver donor to the recipient may further complicate hemostasis during and after transplantation. As a result, consideration of congenital coagulation disorders in the liver donor is a practical concern for donor selection. However, there is no clear consensus regarding selection of donors with known or suspected thrombophilia or bleeding disorders. While multiple case reports and retrospective studies, subject to reporting bias, describe donor-derived thrombophilic and bleeding disorders, there are no large studies in the adult liver transplant literature that examine the frequency of transmission, utility of donor screening, or clinical impact of donor hemostatic disorders. Based on the reported literature, we summarize our approach for donor selection with an aim to balance improved organ utility and optimal post-transplant outcomes.

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“…While FIX is clearly established as hepatocyte‐derived, FVIII mRNA has been found predominately in liver sinusoidal endothelial cells 48,49 . Some extrahepatic synthesis may occur as well 50 . Thus, targeting the liver with gene therapy directs transgene expression to hepatocytes, which for FVIII means expression in a heterologous cell type.…”

Section: The First Wave Of Haemophilia Gene Therapy From the 1980smentioning

confidence: 99%

Uncertainty in an era of transformative therapy for haemophilia: Addressing the unknowns

Pierce

2020

Haemophilia

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Haemophilia is at the dawn of a new era in therapeutic management, one that can generate greater protection from bleeding and a functional cure in some individuals. Prior advances in protein engineering and monoclonal antibody technology have facilitated therapeutic options to maintain decreased risk of bleeding and less burdensome treatment. The use of gene transfer, first proposed in 1971 for monogenic diseases, is emerging as an effective long‐term treatment for a variety of diseases. Transfer of functional factor VIII (FVIII) and factor IX (FIX) genes has witnessed a series of advances and setbacks since the first non‐clinical experiments in animals were initiated nearly 30 years ago. More recently, multiyear therapeutic levels of FVIII and FIX activity have been achieved in human clinical trials, translated into meaningful clinical benefit and a functional cure. While clinical progress has been definitive, many questions remain unanswered as prelicensure phase 3 clinical trials are underway. These unanswered questions translate into a state of uncertainty about the known unknowns and unknown unknowns intrinsic to any new therapeutic platform. Accepting this modality as a means to functionally cure haemophilia also means accepting the uncertainty regarding the biology of viral vector‐mediated gene transfer, which remains inadequately understood. Gene therapy is a far more complex biological ‘drug’ than small molecule and protein drugs, where manufacturing processes and the drugs themselves are now well characterized. Extent of community acceptance of uncertainty and acknowledgement of the need for an uncompromising drive for answers to the unknowns will characterize the introduction of this first generation of gene therapy for haemophilia to the wider patient population in both resource‐rich and resource‐poor countries.

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Successful liver transplant from a hemophilia A donor with no development of hemophilia A in recipient

Cited by 5 publications

References 10 publications

Acquired Hemophilia B Through Liver Transplantation: A Case Report and Literature Review

Acquired Hemophilia B Through Liver Transplantation: A Case Report and Literature Review

Donor-derived disorders of hemostasis and thrombosis in liver transplantation: Considerations for deceased donor liver selection

Uncertainty in an era of transformative therapy for haemophilia: Addressing the unknowns

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