Resistance to activated protein C caused by factor V Leiden mutation and orthotopic liver transplantation.
BACKGROUND
Factor V (FV)-dependent resistance to activated protein C (APCR) is most likely caused by a point mutation in the FV gene, the so-called FV Leiden mutation (FV:Q506), which is a common risk factor predisposing to venous thromboembolism. Little is known about the role of FV:Q506 in recipients of human liver grafts and the significance of acquired APCR caused by orthotopic liver transplantation (OLT).


METHODS
We screened blood samples of 720 patients who underwent OLT by genotyping for FV:Q506 and by testing for APCR with two highly FV-specific tests. Apart from the existing medical records, we obtained clinical data from 551 patients on thromboembolic events (TEs) by means of a questionnaire.


RESULTS
We found 49 (6.8%) heterozygous carriers of FV:Q who did not show APCR after OLT. One patient, heterozygous for FV:Q506, displayed APCR after OLT. In 35 (4.9%) noncarriers of FV:Q we detected APCR after OLT. In comparison with noncarriers, carriers of FV:Q506 demonstrated more TE before transplantation (7% vs. 28%, P<0.0005; relative risk 4.0 [95% confidence interval, 2.3-6.9]); this was also true for Budd-Chiari syndrome (1.8% vs. 10%, P<0.005). At a median follow-up of 5 years (0, 13-12 years), we found a higher incidence of TE after transplantation in patients with "acquired" APCR (16.7% vs. 4,3%; P=0.01; relative risk 3.9 [95% confidence interval, 1.7-9.0]), which included one patient with life-threatening TE during the early postoperative phase.


CONCLUSIONS
APCR caused by FV:Q506 before OLT is a risk factor for TE. OLT-related "acquired" APCR should be considered a risk factor for venous thromboembolism.
Loew
Andreas
A
Medizinische Klinik mit Schwerpunkt Hämatologie und Onkologie, Charité, Campus Virchow-Klinikum, Humboldt-Universität zu Berlin, Germany. andreas.loew@charite.de
Jacob
Dietmar
D
Neuhaus
Peter
P
Riess
Hanno
H
D020016:Activated Protein C Resistance / Q000150:complications / Q000209:etiology / Q000235:genetics*; D000328:Adult; D000368:Aged; D005165:Factor V / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005973:Glutamine; D006579:Heterozygote; D006801:Humans; D015994:Incidence; D016031:Liver Transplantation / Q000009:adverse effects; D008297:Male; D008499:Medical Records; D008875:Middle Aged; D009154:Mutation; D012307:Risk Factors; D016019:Survival Analysis; D013923:Thromboembolism / Q000453:epidemiology / Q000209:etiology; D020246:Venous Thrombosis / Q000453:epidemiology / Q000209:etiology
C095381:factor V Leiden; D005973:Glutamine; D005165:Factor V