Heterozygous protein C deficiency and dysfibrinogenemia acquired by liver transplantation

Abstract

Orthotopic liver transplantation is now a successful treatment for end-stage liver diseases. Since most components of the coagulation system are synthesized by liver parenchymal cells, there is always a risk of genetic defects of hemostasis being transmitting by liver transplantation. Some coagulation factor defects, such as protein C deficiency, do not induce abnormalities in routine coagulation tests and, thus, go undetected before organ procurement. We report the first case, to our knowledge, of the transmission of heterozygous protein C deficiency, an autosomal recessive genetic defect, associated with dysfibrinogenemia, an autosomal dominant trait, by liver transplantation. Both the recipient and the donor presented with severe thrombotic complications. This case shows that potentially morbid genetic defects can be transmitted by organ transplantation, and it emphasizes the difficulty associated with organ procurement criteria, particularly for liver transplantation, in which routine blood tests appear insufficient for determining whether or not organs can or should be procured from a given donor.

Combined congenital dysfibrinogenemia and factor VII deficiency from mutations in the FGB and F7 genes

“…The patient described in the present report had congenital dysfibrinogenemia combined with FVII deficiency. There have been reports on congenital dysfibrinogenemia combined with FV Leiden mutation or protein C deficiency [13][14][15]. Our patient represents the first case of congenital dysfibrinogenemia combined with FVII deficiency confirmed by molecular genetic tests.…”

Severe Thrombotic Complications Associated with Activated Protein C Resistance Acquired by Orthotopic Liver Transplantation

“…Both hemophilia A and B have been cured by liver transplantation [11], while factor XI deficiency has been acquired by this procedure [12]. Similarly, hypercoagulable states may also be affected by liver transplantation, insofar as heterozygous protein C deficiency and dysfibrinogenemia have been acquired by liver transplantation [13]. Conversely, APC resistance due to homozygous FV Leiden was corrected following liver transplantation for acute Budd-Chiari syndrome [14].…”

Factor XII Deficiency Acquired by Orthotopic Liver Transplantation: Case Report and Review of the Literature

“…Our patient represents the first reported case of Factor XII deficiency transmitted by orthotopic liver transplantation. Previous reports have documented liver donor‐to‐recipient transmission of protein C deficiency with dysfibrinogenemia, protein S, factor VII and factor XI deficiencies (1–4).…”

“…Some coagulation defects such as protein C, protein S and antithrombin III deficiency, which are not detected by routine coagulation tests such as the INR and aPTT could be undetected before organ procurement. One patient acquired heterozygous protein C deficiency and dysfibrinogenemia after liver transplantation, and this was associated with severe thrombotic complications (1). Schuetze et al reported a patient who acquired protein S deficiency after undergoing orthotopic liver transplantation.…”

“…However, liver transplantation may be associated with transmission of various deficiencies of proteins synthesized by the liver including coagulation factors. There are published reports of liver donor‐to‐recipient transmission of protein C deficiency with dysfibrinogenemia (1), protein S (2), factor VII (3) and factor XI deficiencies (4). Although some of these factor deficiencies may be benign, others may cause significant illnesses in the recipient.…”