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      Thrombophilic risk factors in hemodialysis: Association with early vascular access occlusion and patient survival in long-term follow-up

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          Abstract

          Objective

          Thrombophilic risk factors (TRFs) occur rather frequently in hemodialysis (HD) patients. However, little is known about their significance in HD patients, besides their potential impact on arteriovenous (AV) access failure, with varying results. We examined the effects of a wide variety of TRFs on both early AV fistula occlusion and survival among HD patients in long-term follow-up.

          Methods

          In this single-center, observational study, 70 consecutive HD patients from our dialysis center were examined with respect to shunt occlusion within the first 2 years after fistula creation and patient survival in a long-term follow-up (at least 16 years). We examined the presence of factor V, prothrombin, and MTHFR mutations using real-time fluorescence polymerase chain reaction. Furthermore, antithrombin (AT), protein C, protein S, and antiphospholipid antibodies (APL-Abs) were assessed.

          Results

          Among the 70 patients, 32 had MTHFR mutations, 10 had heterozygous factor V Leiden mutations, 4 had prothrombin mutations, 4 had protein S deficiency, 2 had protein C deficiency, 9 had AT deficiency, and 14 had APL-Abs. 40 patients had shunt occlusion. TRFs were associated with a significantly increased risk for shunt thrombosis ( P<0.02). Kaplan–Meier analysis with a log-rank test revealed significantly shorter survival in HD patients with TRFs ( P<0.02). Cox regression analysis showed that the presence of TRFs ( P<0.05; hazard ratio, 1.94; 95% CI: 1.07–3.56), but not early shunt occlusion, was associated with short patient survival.

          Conclusions

          TRFs in hemodialysis patients have a strong impact on patient survival and early AV fistula failure; however, patient survival is not significantly affected by early shunt occlusion.

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          Most cited references37

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          Increasing arteriovenous fistulas in hemodialysis patients: problems and solutions.

          National guidelines promote increasing the prevalence of fistula use among hemodialysis patients. The prevalence of fistulas among hemodialysis patients reflects both national, regional, and local practice differences as well as patient-specific demographic and clinical factors. Increasing fistula prevalence requires increasing fistula placement, improving maturation of new fistulas, and enhancing long-term patency of mature fistulas for dialysis. Whether a patient receives a fistula depends on several factors: timing of referral for dialysis and vascular access, type of fistula placed, patient demographics, preference of the nephrologist, surgeon, and dialysis nurses, and vascular anatomy of the patient. Whether the placed fistula is useable for dialysis depends on additional factors, including adequacy of vessels, surgeon's experience, patient demographics, nursing skills, minimal acceptable dialysis blood flow, and attempts to revise immature fistulas. Whether a mature fistula achieves long-term patency depends on the ability to prevent and correct thrombosis. An optimal outcome is likely when there is (1) a multidisciplinary team approach to vascular access; (2) consensus about the goals among all interested parties (nephrologists, surgeons, radiologists, dialysis nurses, and patients); (3) early referral for placement of vascular access; (4) restriction of vascular access procedures to surgeons with demonstrable interest and experience; (5) routine, preoperative mapping of the patient's arteries and veins; (6) close, ongoing communication among the involved parties; and (7) prospective tracking of outcomes with continuous quality assessment. Implementing these measures is likely to increase the prevalence of fistulas in any given dialysis unit. However, differences among dialysis units are likely to persist because of differences in gender, race, and co-morbidity mix of the patient population.
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            Outcomes of vascular access for hemodialysis: A systematic review and meta-analysis.

            The decision about the type and location of a hemodialysis vascular access is challenging and can be affected by multiple factors. We explored the effect of several a priori chosen patient characteristics on access outcomes.
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              Hemodialysis vascular access morbidity.

              Complications associated with hemodialysis vascular access represent one of the most important sources of morbidity among ESRD patients in the United States today. In this study, new data on the magnitude and growth of vascular access-related hospitalization in the United States is presented, demonstrating that the costs of this morbidity will soon exceed $1 billion per yr. This study also reviews published literature on the morbidity associated specifically with native arteriovenous fistulae, polytetrafluoroethylene bridge grafts, and permanent central venous catheters. Next, new information on the changing patterns of vascular access type in the United States is presented, demonstrating the continuing evolution of medical practice away from the use of arteriovenous fistulae in favor of more reliance on synthetic bridge grafts. Based on these data, a discussion is provided of the tradeoffs among the most commonly available modalities of vascular access today. Although radial arteriovenous fistulae continue to represent the optimal access modality, the appropriate roles for brachial arteriovenous fistulae, synthetic bridge grafts, and central venous catheters are less certain because of inadequate data on the long-term function of the first and the high rates of complications associated with the latter two. To reduce vascular access-related morbidity, strategies must be developed not only to prevent and detect appropriately early synthetic vascular access dysfunction, but to better identify the patients in a whom radial arteriovenous fistula is a viable clinical option.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Writing – original draft
                Role: Data curationRole: Formal analysisRole: Investigation
                Role: Formal analysisRole: MethodologyRole: ValidationRole: Visualization
                Role: ConceptualizationRole: ValidationRole: VisualizationRole: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: Project administrationRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                20 September 2019
                2019
                : 14
                : 9
                : e0222102
                Affiliations
                [001]Department of Nephrology and Rheumatology, Georg-August University, Goettingen, Germany
                University of Missippi Medical Center, UNITED STATES
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                [¤]

                Current address: Department of Nephrology, Hypertension and Rheumatology, Academic Teaching Hospital Bamberg, Bamberg, Germany

                Author information
                http://orcid.org/0000-0003-4300-5293
                Article
                PONE-D-19-11353
                10.1371/journal.pone.0222102
                6754127
                31539375
                58e97b0c-f889-42ec-8553-0a9e62e3caf0
                © 2019 Grupp et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 21 April 2019
                : 21 August 2019
                Page count
                Figures: 5, Tables: 4, Pages: 15
                Funding
                The authors received no specific funding for this work.
                Categories
                Research Article
                Medicine and Health Sciences
                Nephrology
                Medical Dialysis
                Medicine and Health Sciences
                Diagnostic Medicine
                Signs and Symptoms
                Fistulas
                Medicine and Health Sciences
                Pathology and Laboratory Medicine
                Signs and Symptoms
                Fistulas
                Medicine and Health Sciences
                Hematology
                Blood Coagulation
                Coagulation Disorders
                Medicine and Health Sciences
                Cardiovascular Medicine
                Cardiovascular Diseases
                Coagulation Disorders
                Medicine and health sciences
                Hematology
                Blood coagulation
                Coagulation disorders
                Protein C deficiency
                Medicine and health sciences
                Cardiovascular medicine
                Cardiovascular diseases
                Coagulation disorders
                Protein C deficiency
                Biology and Life Sciences
                Biochemistry
                Enzymology
                Enzymes
                Proteases
                Serine Proteases
                Biology and Life Sciences
                Biochemistry
                Proteins
                Enzymes
                Proteases
                Serine Proteases
                Medicine and health sciences
                Hematology
                Blood coagulation
                Coagulation disorders
                Factor V Leiden
                Medicine and health sciences
                Cardiovascular medicine
                Cardiovascular diseases
                Coagulation disorders
                Factor V Leiden
                Medicine and Health Sciences
                Epidemiology
                Medical Risk Factors
                Medicine and Health Sciences
                Surgical and Invasive Medical Procedures
                Transplantation
                Organ Transplantation
                Renal Transplantation
                Medicine and Health Sciences
                Surgical and Invasive Medical Procedures
                Urinary System Procedures
                Renal Transplantation
                Custom metadata
                Data cannot be shared publicly because of confidential patient data. Data are available from the Department of Nephrology and Rheumatology, Georg August-Universtity Göttingen, Germany, for researchers who meet the criteria for access to confidential data. Interested researchers may request data access by e-mail: nephrorheuma@ 123456med.uni-goettingen.de .

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