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Santler, S.
The impact of MTHFR mutations on the primary patency of PTFE haemodialysis shunt prostheses
Humanmedizin; [ Diplomarbeit/Master Thesis (UNI) ] Graz Medical University; 2017. pp.55. [OPEN ACCESS]
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Authors Med Uni Graz:
Schiffmann Stefanie Christine
Advisor:
Konstantiniuk Peter
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Abstract:
Objectives Currently in persons with heterozygous MTHFR mutations medical protection against thromboembolic events is not recommended. Autologous arteriovenous fistulas should be preferred over arteriovenous (AV) grafts, as access for hemodialysis in patients with end-stage renal disease. Primary patency, defined as the time between graft implantation and the first shunt thrombosis, of implanted PTFE grafts at our institution is 23.3 months. Currently it is unknown whether heterozygous MTHFR mutations have an influence on the primary patency of PTFE grafts . 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 were drawn retrospectively. Genetic typing, including MTHFR mutation, Factor V Leiden thrombophilia and Prothrombin G20210A mutation were performed. Additionally a thrombophilia screening including homocysteine, lipoprotein a, activated protein C resistance (APCR), protein C activity, fractionated protein S antigen, lupus sensitive activated partial thromboplastin time (aPTT), lupus anticoagulant (LA), anti-cardiolipin antibodies and ß2-glycoprotein antibodies was executed. Some (76) of the shunts had to be excluded due to several reasons such as death and revision. Statistical analysis was performed with SPSS 23.0.0.0. Primary patency (PP) was calculated using the Kaplan Meier method whereas differences between subgroups were identified with Cox regression analysis. A p-value under 0.05 was considered significant. Results The overall primary patency for the 59 grafts was 17.26 months. Two of the investigated factors revealed significant differences (table 2): table 2: Primary patency [M] of APCR and anti-cardiolipin antibodies and their p-values (P) ValuePP [M]P APCR< 2.96.40.001 = 2.917.6 anti-cardiolipin antibodies= 2.524.50.05 > 2.59.1 11.9 % of the patients had a factor V Leiden thrombophilia (heterozygous + homozygous). All of them had pathologic activated protein C resistance (APCR) values and a significantly lower primary patency (PP). Conclusions Patients with Factor V Leiden mutations in general only need protection against thromboembolic events in high risk situations (pregnancy, immobilization). Our data reveal that the use of PTFE shunt grafts puts the patients at risk for thromboembolic events so these particular individuals should be put on oral anticoagulation. To reduce the frequency of thrombectomies, patients should undergo thrombophilia screening before a PTFE shunt graft is implanted. The anti-cardiolipin antibodies were significantly associated with a low PP, which is surprising because the anti-cardiolipin antibodies levels of all patients were within the "normal" range, thus we are not able to draw conclusions with sufficient power, further studies are needed for that particular issues.

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