Role of Genetic Factors in Vascular Access Thrombosis in Hemodialysis Patients

Abstract

Vascular access thrombosis is a frequent complication in hemodialysis (HD) patients. Genetic mutations, inflammation, and changes in the vascular wall are some factors that are thought to increase thrombosis risk. In this study, we tested for possible relationships between vascular thrombosis and some known thrombophilic mutation/polymorphisms in coagulation factors [factor V Leiden (FVL), prothrombin (Pt) G20210A, methylene tetrahydrofolate reductase (MTHFR C677T), factor XIII (F‐XIII) Val34Leu, alpha‐fibrinogen (AF) Thr312Ala, factor VII (F‐VII) R353Q] and angiotensin I converting enzyme (ACE) gene in our HD patients. Patients who had experienced at least 3 episodes of AVF thrombosis composed of the study group, and patients who had never encountered this complication composed of the control group. None of the patients in either group had a history of diabetes mellitus, atherosclerosis, dialysis‐related amyloidosis, or vasculitis. In order to find the frequency of F‐XIII Val34Leu, AF Thr312Ala, and F‐VII R353Q polymorphisms in our population, we also searched persons without renal disease or history of thrombosis (normal group). Results are summarized in Table. There was a tendency toward thrombotic mutation/polymorphisms in the study group for FVL, Pt G20210A, ACE I/D, and AF Thr312Ala. We suggest that patients who develop recurrent AVF thrombosis should be screened for the above‐mentioned factors and investigated for other possible risk factors. This screening would allow more effective focus on prophylaxis. Genetic mutation/ polymorphism Study group Normal group Control group FVL/heterozygous 13 (n = 46) 7 (n = 81) 24.5 (n = 44) Pt G20210A/ heterozygous 8.7 (n = 46) 2.7 (n = 182) 20 (n = 44) MTHFR C677T/ heterozygous 0 (n = 44) 28.8 (n = 66) 22.3 (n = 44) ACE I/DD/D 44.5 (n = 44) 28.8 (n = 138) 26.2 (n = 29) I/D 36.3 (n = 44) 47.2 (n = 138) 23.1 (n = 29) I/I 18.2 (n = 44) 15.4 (n = 138) 27 (n = 29) F‐XIII/ Val34LeuVal/Val 44.8 (n = 29) 71.5 (n = 112) 52 (n = 25) Val/Leu 51.8 (n = 29) 27.6 (n = 112) 48 (n = 25) Leu/Leu 3.4 (n = 29) 0.9 (n = 112) 0 (n = 25) AF Thr312AlaAla/Thr 83 (n = 24) 58 (n = 119) 83.3 (n = 30) Thr/Thr 12.5 (n = 24) 32.6 (n = 119) 10 (n = 30) Ala/Ala 4.5 (n = 24) 8.4 (n = 119) 6.7 (n = 30) F‐VII R353QR/R 39 (n = 18) 74.5 (n = 98) 31.8 (n = 22) R/Q 34 (n = 18) 23.5 (n = 98) 68.2 (n = 22) Q/Q 27 (n = 18) 2 (n = 98) 0 (n = 22) Values are percentages and numbers in parenthesis represent the number of patients/persons studied.