Discrepancy between Phenotype and Genotype for Factor V Leiden Mutation in Recipients of Liver Transplant.
Authors: Ayala Rosa M. , Martin Maria Angeles , Martinez Joaquin , Meneu Juan Carlos , Moreno Almudena , Toledo Teresa , De la Serna Javier , Ribera Carmen 
Published: April 2020

Abstract
Factor V (FV) Leiden is the most common genetic mutation associated to thrombophilia in the European population. The study of FV Leiden uses genetic tests and functional coagulative tests which detect the resistance of activated FV to the action of activated protein C (APC), and measure the phenotypic expression of FV Leiden. Factor V is mainly synthetized by hepatocytes with only a smaller pool originating from megakariocytes. Due to this, in an recipient liver transplantation the characteristics of the donor’s FV will be transmitted with the liver graft. OBJECTIVE.- To evaluate the possible discordance between genotype and phenotype of FV Leiden in recipients of human liver grafts.
METHODS.- Genetic study of FV Leiden and functional coagulative tests detecting the resistance to APC were performed on samples of peripheral blood of 97 recipients of liver transplantation, after transplant, in our institution. In addition, a genetic study of FV Leiden was performed on frozen serum samples of 51 dead donors, obtained prior to the liver extraction. The functional test was carried out by coagulative technique in a coagulometer STA with Coatest APC Resistance (Chromogenix). To perform the genetic test genomic DNA was obtained, and the determination of mutations was carried out by PCR in real time, using hybridation probes in a Light-Cycler system (Roche Biomedical).
RESULTS.- From the 97 recipients, 3 were heterozygous for FV Leiden in peripheral blood (3.1%). Resistance to APC was normal in all three cases: 3.17, 3.23 and 2.36 (normal 2..4). FV Leiden was not detected in the genetic study performed on the respective donors’ serum. From these 3 recipients, 1 underwent a portal thrombosis event prior to the transplantation, another had a familiar history of thrombosis, and the third one did not have personal or familiar antecedents prior to transplantation. None of them showed thrombotic complications after transplantation. In the studies carried out on the donor’s serum (51) only one case of heterozygous FV Leiden was detected (1.96%). In the associated recipient FV in blood was negative and the resistance to APC was 1.88 diluting the plasma under study with plasma deficient in FV (normal 2– 4). This patient did not show thrombotic events before or after transplantation.
CONCLUSION.- This study shows the discordance between phenotype and genotype of FV Leiden in recipients of liver grafts and the need to evaluate both genotype and phenotype to assess the thrombotic risk after transplantation. The risk depends mainly on the donor’s genotype, due to the production of mutant FV by donor hepatocytes. Therefore, in the four patients with discrepancy between phenotype and genotype of FV Leiden, the risk of venous thromboembolism would not be significantly increased in the three recipients with heterozygosity for FV Leiden y resistance to APC normal and in contrast the fourth patient with acquired resistance to APC might have an increased risk despite a normal FV genotype in peripheral blood leukocytes