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Can screening for genetic markers improve peripheral artery bypass patency?
Melina R Kibbe1, Andrea L Cortese Hassett, Frances McSherry
1Division of Vascular Surgery, University of Pittsburgh, 200 Lothrop Street, Pittsburgh, PA 15213, USA.
Insights
Genetic mutations like factor V Leiden and prothrombin do not increase thromboembolic risk after peripheral bypass. However, methylenetetrahydrofolate reductase (MTHFR) heterozygosity improves graft patency, while homozygosity is linked to thrombosis.
Area of Science:
- Vascular Surgery
- Genetics
- Thrombosis
Background:
- Factor V Leiden, prothrombin, and MTHFR mutations are linked to thromboembolic events.
- The impact of these genetic mutations on peripheral bypass outcomes is not fully understood.
Purpose of the Study:
- To investigate the effect of factor V Leiden, prothrombin, and MTHFR mutations on peripheral bypass patency.
- To assess the association between these mutations and preoperative/postoperative thromboembolic events.
Main Methods:
- 244 volunteers from Veterans Affairs Cooperative Study #362 were genotyped for MTHFR, factor V Leiden, and prothrombin mutations.
- Patients received aspirin or aspirin/warfarin post-bypass.
- Thromboembolic events and graft patency (PP, APP, SP) were compared among mutation carriers and wild-type subjects.
Main Results:
- MTHFR homozygous patients showed increased graft thrombosis (33.3%) and lower patency rates compared to heterozygotes.
- MTHFR heterozygous patients exhibited fewer graft thromboses (11.1%), fewer amputations, and superior patency rates versus wild-type controls.
- Factor V Leiden and prothrombin mutations did not correlate with increased risk of graft occlusion or thromboembolic events.
Conclusions:
- Factor V Leiden and prothrombin mutations do not appear to increase risk for peripheral bypass complications.
- MTHFR heterozygosity is associated with improved graft patency and reduced thrombosis after bypass.
- Preoperative MTHFR screening may identify patients at higher risk for graft thrombosis, guiding surgical management.
Objective:
Three genetic mutations have been associated with an increased risk of thromboembolic events: factor V Leiden R506Q, prothrombin G20210A, and methylenetetrahydrofolate reductase C677T (MTHFR) mutations. The aim of this study was to determine the effect of these mutations on patency of peripheral bypass procedures and preoperative and postoperative thromboembolic events.
Methods:
Two hundred forty-four randomly selected volunteers participating in the Veterans Affairs Cooperative Study #362 were tested for factor V Leiden, prothrombin, or MTHFR mutations with polymerase chain reaction. Patients enrolled in the study were randomized to receive aspirin therapy or aspirin and warfarin therapy after a peripheral bypass procedure. The frequencies of preoperative and postoperative thromboembolic events and primary patency (PP), assisted primary patency (APP), and secondary patency (SP) rates were compared among carriers of the various mutations.
Results:
Fourteen patients (5.7%) were heterozygous for the factor V Leiden mutation, seven (2.9%) were heterozygous for the prothrombin mutation, and 108 (44.6%) were heterozygous and 15 (6.2%) homozygous for the MTHFR mutation. After surgery, patients homozygous for the MTHFR gene mutation had increased graft thrombosis, compared with patients who were heterozygous (33.3% versus 11.1%; P =.01), and lower PP, APP and SP rates (P <.05). Furthermore, patients heterozygous for the MTHFR mutation had fewer graft thromboses (11.1% versus 24.4%; P =.01), fewer below-knee amputations (0.9% versus 7.6%; P =.02), and higher PP, APP, and SP rates (PP, 79.6%; APP, 88.9%; SP, 90.7%; P <.05) compared with wild-type control subjects (PP, 63%; APP, 75.6%; SP, 76.5%; P <.05).
Conclusion:
Patients with either factor V Leiden or prothrombin mutations were not at an increased risk for postoperative graft occlusion or thromboembolic events. Patients heterozygous for MTHFR mutation had a lower risk of graft thrombosis and higher graft patency rates compared with both homozygous and wild-type control subjects. Patients homozygous for the MTHFR mutation had lower graft patency rates compared with patients who were heterozygous, and a trend was seen toward lower patency rates compared with wild-type control subjects. Therefore, screening for the MTHFR gene mutation before surgery may identify patients at an increased risk of graft thrombosis.
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