Cohort Study of Thrombophilia and Thombotics Events in Recipients of Liver Transplantation and Their Respective Donors.

Background: The prothrombin G20210A (FII G20210A) and Factor V (FV) Leiden polymorphisms are the most common hereditary risk factors for venous thromboembolism. Little is known about the role of the thombophilic factors on the risk of thromboembolic events (TE) in recipients of orthotopic liver transplantation (OLT). This study aims to evaluate the influence of the recipients’ genetic mutations (FII G20210A, FV Leiden and methilene tetrahydrofolate reductase (MTHFR) C677T homozygosity) on the incidence of TE before OLT; and those acquired with the grafted liver (FII G20210A, FV Leiden-resistance to activated protein C, MTHFR C677T homozygosity and other trombophilic factors) on the risk of TE after the OLT.

Patients and Methods: Between January 2001 and July 2006, 378 OLT, including 23 retransplantations, were performed in our institution. Clinical data were available on 341 patients. In 255 recipients, genetic and functional tests were performed after OLT and included FII G20210A, FV Leiden and MTHFR C677T, PT, APTT, fibrinogen, antithrombin, protein C, protein S, resistance to activated protein C, FVIII activity, anticoagulant lupus study, anticardiolipin antibodies and homocystein. Samples for FII G20210A, FV Leiden and MTHFR C677T were obtained for 155 donor grafts (112 deceased and 39 live donors). The genetic mutations were detected by real-time PCR technology.

Results: From 341 patients with clinical data available, 42 suffered TE before OLT and 30 patients after OLT. Among the 255 recipients whom genetic studies were performed, 10 carriers of FV Leiden (2.7%), 16 carriers of FII G2010A09 ((3.9%) and 31 homozygous MTHFR C677T (12.2 %) were found. The incidence of TE before transplantation was similar for carriers and noncarriers of the genetic trombophilic alterations (FV Leiden: 1.5% vs 2.1%; FII G20210A: 0% vs 4.9%; MTHFR C677T: 13% vs 11%). Among the donors we found 1 carrier of FV Leiden (0.6%), 4 carriers of FII G20210A (2.2%), and 24 homozygous MTHFR C677T (9.4%). We did not find significant differences in the incidence of TE after OLT in recipients of a grafted liver with or without genetic thrombophilic alterations (FV Leiden: 0% vs 0.8%; FII G20210A: 0% vs 2.5%; MTHFR C677T: 7.7% vs 7.5%). A correlation between high FVIII levels and post OLT thrombosis was found (p: 0.007). Other phenotypic studies after transplantation were similar on patients with and without thrombosis.

Conclusion: The incidence of TE before transplantation is similar for carriers and noncarriers of FII G20210A, FV Leiden and homozygous MTHFR C677T. The presence of FII G20210A, FV Leiden and homozygous MTHFR C677T on the donors did not increased the risk of TE after OLT. This study adds information about an unclear aspect of thrombophilia in OLT. Further studies are required to clarify the reasons for the association of high levels of FVIII with vascular thrombosis after OLT. This study was funded by FMM 2004/009.