The impact of MTHFR mutations on the primary patency of PTFE haemodialysis shunt prostheses

Abstract

Objectives For performing haemodialysis patients often get an arteriovenous shunt. Ideally, this is made of a body's own vein (autologous vein). If there is no such vein available, a plastic shunt may also be implanted, although the rate of thromboses is much higher. The most frequently used plastic is PTFE (Polytetrafluoroethylene). According to current doctrine people with an asymptomatic heterozygous MTHFR (methylenetetrahydrofolate reductase) mutation need no medical protection against thromboembolic events. Currently it is unknown, whether patients with PTFE grafts and heterozygous MTHFR mutations have a higher thrombosis rate and therefore need medical protection from thrombosis. The aim of this study is to examine whether MTHFR mutation has an impact on the primary patency (PP). PP is defined as the time between graft implantation and the first shunt thrombosis. Material and Methods From 2009 to 2014 135 PTFE grafts were implanted at the Medical University of Graz. For this study 43 patients with 59 shunts could be included. Blood was taken for determination of various thrombophilic factors, clinical data was drawn retrospectively. Genetic typing, including MTHFR mutation, Factor V Leiden thrombophilia and prothrombin G20210A mutation, was performed. Additionally a thrombophilia screening was executed. The PP was statistically evaluated in relation to the results of the thrombophilia screening and the genetic typing. Corresponding p-values were determined. Results The overall primary patency for the 43 patients was 18.44 months (± 3.16 SE). The mean age of the 43 patients at the time of shunt implantation was 63.71 (± 1.62 SE, range 40.03 - 82.10) years. The primary aim was the heterozygous MTHFR mutation. With a p-value of 0.370, it was not significant. APCR was significant with a p-value of 0.005. The Factor V Leiden mutation had a p-value of 0.141 and was not significant. Homocystein (p = 0.485), lipoprotein a (p = 0.893), protein C activity (p = 0.257) and the fractionated protein S antigen (p = 0.149) were not significant as well. Neither the lupus aPTT had a significant p-value (p = 0.226) nor the lupus anticoagulant was significant (0.565). Also the anti-cardiolipin antibodies (p = 0.075) and the ß2-glycoprotein antibodies (p = 0.153) had no significant p-values. 32.6 % of the 43 patients with a primary patency of 19.6 months (± 4.7 SE) did not have a MTHFR mutation. 55.8 % were heterozygous with a primary patency of 15.6 months (± 4.0 SE) and 11.6 % were homozygous for MTHFR with a primary patency of 21.8 months (± 7.2 SE). The main part (90.7 %) of the 43 patients had no Factor V Leiden thrombophilia. 7.0 % were heterozygous and 2.3 % were homozygous for this mutation. This means that 9.3 % of the patients with prostheses had a Factor V Leiden mutation (heterozygous or homozygous). All of them had pathologic activated protein C resistance (APCR) values. There was no prothrombin G20210A mutation found in any of the 43 patients. Conclusions An impact on the primary patency of the heterozygous MTHFR mutation could not be proven in this study. It is a common doctrine, that patients with Factor V Leiden mutations (heterozygous or homozygous) have pathologic activated protein C resistance (APCR) values and in general only need protection against thromboembolic events in high risk situations (pregnancy, immobilization). Our data revealed that the use of PTFE shunt grafts puts the patients at risk for thromboembolic events. Those particular patients should also be treated with oral anticoagulation. To reduce the frequency of unnecessary thrombectomies and to prolong primary patency, we advice that patients undergo thrombophilia screening before a PTFE shunt graft is implanted. An impact of the heterozygous MTHFR mutation on the primary patency could not be proven in this study.

Datum der Bewilligung	2017
Originalsprache	Englisch
Gradverleihende Hochschule	Medizinische Universität Graz
Betreuer/-in	Peter Konstantiniuk (Betreuer*in)