Access Thrombosis In Hemodialysis Patients Research Articles

Role of Neutrophil Extracellular Traps in Vascular Access Thrombosis in Hemodialysis Patients

Role of Neutrophil Extracellular Traps in Vascular Access Thrombosis in Hemodialysis Patients

Role of neutrophil extracellular traps in vascular access thrombosis in hemodialysis patients

BackgroundA patent vascular access (VA) is a lifeline for hemodialysis (HD) patients. However, vascular access is prone to thrombosis, which, if left untreated, can lead to permanent VA loss and increased mortality. Neutrophil extracellular traps (NETs) are known to be involved in intravascular thrombosis. We evaluated the relationship between NETs and VA thrombosis and their impact on VA prognosis. MethodsA total of 189 patients with VA flow problems were enrolled. Among these, 93 patients underwent percutaneous transluminal angioplasty (PTA) for stenosis, and 96 patients underwent PTA with thrombectomy for thrombosis. Plasma nucleosome, myeloperoxidase-DNA complex, and von Willebrand factor (vWF) were measured as markers of circulating NETs and thrombosis risk, respectively. The primary outcome was permanent VA loss and the secondary outcome was recurrent thrombotic occlusion within 6 months. In addition, the presence of NETs in thrombi was evaluated by histopathological analysis. ResultsCirculating nucleosome levels were closely associated with plasma vWF levels (r = 0.172, p = 0.025), and both were higher in thrombectomy cases than in PTA alone cases (nucleosome; 0.83 ± 0.70 vs. 0.35 ± 0.26, p < 0.001, vWF: 9.0 ± 7.6 vs. 7.3 ± 6.2, p = 0.038). The highest quartile of nucleosomes (Q4) was associated with an 18-fold increased rate of access thrombotic occlusion (p < 0.001). In addition, multivariate analysis showed that the rates of permanent access loss (HR 2.77, 95 % CI 1.35–5.77) and recurrent thrombosis (HR 2.35, 95 % CI 1.22–4.54) were much higher in patients with the Q4 nucleosome group than in those with Q1–3. In addition, higher neutrophil infiltration and NET expression in thrombi were also associated with poor VA prognosis. ConclusionsHigher levels of circulating NETs and the amount of NET expression in thrombi may be associated with VA thrombosis and poor VA outcomes.

Neutrophil extracellular traps and heparin-induced antibodies contribute to vascular access thrombosis in hemodialysis patients.

BackgroundAnti-heparin/platelet factor 4 (PF4) antibodies may trigger severe thrombotic complications in hemodialysis (HD) patients. Tetrameric PF4 has a high affinity for extracellular DNA, which is a key component of neutrophil extracellular traps (NETs); therefore, the interactions between anti-heparin/PF4 antibodies and NETs can contribute to prothrombotic events.MethodsAnti-heparin/PF4 antibody levels were measured by enzyme-linked immunosorbent assay and an optical density > 1.8 was regarded as clinically significant. We additionally measured serum nucleosome levels as representative markers of NETs, and the contributions of anti-heparin/PF4 and increased serum nucleosome levels to the primary functional patency loss of vascular access was assessed.ResultsThe frequency of anti-heparin/PF4 antibodies was significantly higher in incident HD patients compared to prevalent HD patients (23.6% vs. 7.7%). Serum nucleosome levels, as well as the white blood cell counts, neutrophil counts, and high- sensitivity C-reactive protein levels, were significantly higher in anti-heparin/PF4 antibody-positive patients compared to the control. Platelet counts tended to be lower in the patients with anti-heparin/PF4 of >1.8 than in the controls. Relative risk calculations showed that the presence of anti-heparin/PF4 antibodies increased the risk of primary functional patency failure by 4.28-fold, and this risk increased further with higher nucleosome levels. Furthermore, in the anti-heparin/PF4 antibody-positive group, the time to first vascular intervention was much shorter, and the risk of repeated intervention was higher, compared to the controls.ConclusionIn incident HD patients, the presence of anti-heparin/PF4 antibodies was associated with increased NET formation; this could be a strong predictor of vascular access complications

Pulmonary embolism with endovascular thrombolysis for thrombosed hemodialysis arteriovenous access .

Acute thrombosis of hemodialysis (HD) arteriovenous access is an urgent problem for HD patients and is commonly managed by endovascular thrombolysis. Pulmonary embolism (PE) is a recognized complication of HD access thrombosis and thrombolysis but the risk and outcomes are unclear. This study aims to determine the incidence, predictors, and outcomes of PE after endovascular thrombolysis of HD arteriovenous access in patients presenting with acute thrombosis. A single-center retrospective study was performed for all adult chronic kidney disease patients undergoing arteriovenous access thrombolysis between January 1, 2012, and December 31, 2014. Investigation for PE with CT pulmonary angiography or ventilation/perfusion scintigraphy (V/Q scan) was performed as clinically directed by the managing clinicians. In cases diagnosed with PE, the pulmonary embolism severity index (PESI) was calculated. A total of 48 (median age 68) patients underwent 74 thrombolysis procedures. Thrombolysis techniques were divided into pharmacological (44.6%), mechanical (17.6%), or pharmacomechanical (37.8%). Clinical success was achieved in 56/74 (75.7%) of procedures. Five episodes of thrombolysis for access thrombosis (6.8%) were associated with clinically symptomatic PE. The PESI score ranged from 51 to 127. All patients with PE were managed with 3-6 months of anticoagulation and recovered clinically. There were no statistically significant differences in baseline characteristics, methods of thrombolysis, or clot burden in patients that developed a PE. There is a clinically significant risk of symptomatic PE after arteriovenous access thrombolysis for access thrombosis in HD patients. .

Association Between Thrombophilic Gene Mutations and the Risk of Vascular Access Thrombosis in Hemodialysis Patients.

The cause of thrombosis in hemodialysis vascular access is considered to be of a multifactorial nature, including stenosis of the venous or arterial connection. Therefore, identification of relevant thrombotic risk factors could lead to an improved antithrombotic therapy. This case control study was performed to evaluate the relationship between Factor V (G1691A and A4070G) and Factor II polymorphisms and vascular access thrombosis in hemodialysis patients. One hundred and twenty-one patients undergoing dialysis were selected as subjects. This sample was divided into two groups; a case group of 60 patients who had sustained one or more thrombotic events that resulted in vascular access failure and a control group of 61 patients, who never had a thrombotic occlusion of a functioning permanent dialysis access. Our data demonstrated a significantly increased risk of vascular access thrombosis in carriers of the mutant FV (G1691A and A4070G) polymorphisms (P < 0.05).Further studies on a large-scale population and other genetic variants will be needed to find candidate genes for vascular access thrombosis in hemodialysis patients.

Hyperhomocysteinemia and vascular access thrombosis in hemodialysis patients: a retrospective study

BackgroundElevated total plasma homocysteine is an independent risk factor for arterial and venous thrombosis in patients with normal renal function. Patients on hemodialysis have a high prevalence of mild to moderate hyperhomocysteinemia. Conflicting retrospective analyses and prospective studies have been reported regarding the association between total homocysteine levels and hemodialysis vascular thrombosis. The purpose of this retrospective study was to investigate the relationship between hyperhomocysteinemia and vascular access thrombosis (VAT) in patients on hemodialysis.MethodsOne hundred and twenty-five patients undergoing dialysis were selected as subjects. The experimental group participants were identified as those having one or more VAT during the previous 13 months and the control group participants had no access thrombosis during the same period. Additional subgroup analysis included the presence of hypertension, diabetes, low-density lipoprotein levels, sex, and use of aspirin.ResultsNo statistically significant difference was found in total homocysteine levels between the two groups (P = 0.27). No association was found between VAT and sex (P = 0.09), VAT and hypertension (P = 0.96), VAT and diabetes (P = 0.49), nor VAT and low-density lipoprotein level (P = 0.04). A lower rate of VAT was associated with aspirin intake (P = 0.04).ConclusionThis study did not demonstrate a relationship between total homocysteine concentrations and risk of VAT in patients with end-stage renal disease on hemodialysis. There were no significant differences in the number of VAT across additional variables of sex and previous morbidity. Aspirin intake was associated with a lower incidence of VAT.

Inherited protein S deficiency due to a novel nonsense mutation in the PROS1 gene in the patient with recurrent vascular access thrombosis: A case report

Vascular access thrombosis is one of the major causes of morbidity in patients maintained on chronic hemodialysis. Thrombophilia has been recognized as a risk factor of vascular access thrombosis. The authors report a case of inherited protein S deficiency associated with vascular access thrombotic events. DNA sequence analysis of the PROS1 gene identified a novel heterozygous nonsense mutation in exon 10 by transition of AAG (lysine) to TAG (stop codon) at codon 473 (c.1417A>T, p.K473X). Results from the study suggest that the inherited protein S deficiency due to a PROS1 gene mutation may cause vascular access thrombosis in hemodialysis patients.

Role of Thrombophilia in Vascular Access Thrombosis Among Chronic Hemodialysis Patients in Tunisia

Vascular access thrombosis represents a serious and common problem in hemodialysis patients. Therefore, identification of relevant thrombotic risk factors could lead to an improved antithrombotic therapy. This case control study was performed to evaluate the relationship between some thrombophilias and vascular access thrombosis in hemodialysis patients. Seventy-eight patients undergoing dialysis (between May 2007 and September 2009) were selected as subjects. This sample was divided into two groups; a case group of 28 patients who had sustained one or more thrombotic events that resulted in vascular access failure and a control group of 50 patients, who had never had a thrombotic occlusion of a functioning permanent dialysis access. Antithrombin, protein C and protein S levels were measured. Also, both groups were tested for the factor V Leiden mutation, the prothrombin G20210A mutation, the methylene tetrahydrofolate reductase C677T and A1298C mutations. Among genetic mutations of factor V Leiden, prothrombin G20210A and methylene tetrahydrofolate reductase genes, the C677T methylene tetrahydrofolate reductase mutation was the only significant genetic cause of vascular access thrombosis (P=0.005). Our data demonstrated a significantly increased risk of vascular access thrombosis in carriers of the C677T methylene tetrahydrofolate reductase mutation.

C-Reactive Protein Predicts Vascular Access Thrombosis in Hemodialysis Patients

Background: Vascular access thrombosis (VAT) is one of the most common morbidity in hemodialysis patients. The development of arteriovenous fistula thrombosis is associated with vascular intimal hyperplasia. Some studies suggested that serum C-reactive protein (CRP) predicts the development of vascular intima hyperplasia that conduces vascular access stenosis and thrombosis. This study aimed to access the clinical usefulness of CRP in predicting VAT in hemodialysis patients. Methods: We retrospectively reviewed all prevalent hemodialysis patients with native arteriovenous fistula (nAVF) between November 2001 and November 2004. The CRP levels and relation to the development of VAT was analyzed with Kaplan-Meier analysis in four groups of patients divided according to their serum CRP levels. Besides serum CRP levels, other factors possibly influencing vascular access thrombosis were also considered: gender, age, diabetes, aspirin, smoking, statin, serum albumin, hematocrit, cholesterol >200 mg/dl, Calcium-phosphate product, and intact parathyroid hormone >200 pg/ml. Results: We retrospectively reviewed 223 chronic hemodialysis patients. 198 patients with forearm nAVF and 25 with upper arm nAVF were included. Of the above 223 patients, 51 experienced one or more VAT episodes. In Kaplan-Meier survival analysis, patients with serum CRP levels >0.8 mg/dl were prone to develop VAT (log-rank, p < 0.001). In a multivariate Cox regression model, serum CRP greater than 0.8mg/dl was confirmed to be an independent predictor of VAT with a relative risk of 16.6 times (95% CI, 7.85–35.1). The area under the receiver operator characteristic (ROC) curve of CRP >0.8 mg/dl in predicting VAT events is 0.785 (95% CI, 0.712–0.858; p < 0.001). Sensitivity and specificity of CRP (>0.8 mg/dl) in predicting VAT were 80.4 and 72.7%. Conclusions: The serum CRP levels not only predict cardiovascular disease and mortality in hemodialysis patients but also predict the development of vascular access thrombosis in chronic hemodialysis patients.

High Prevalence of Antibodies to the Heparin-Platelet Factor 4 Complex in Hemodialysis Patients.

Heparin-induced thrombocytopenia is a serious complication of systemic heparin therapy. Patients with this disorder develop antibodies to the heparin-platelet factor 4 (H-PF4) complex. Patients with H-PF4 antibodies are at higher risk of venous and arterial thrombosis independently of the platelet count. Hemodialysis (HD) patients are repeatedly exposed to heparin to prevent thrombosis of the extra-corporeal circuit. However, thrombosis remains a frequent complication of vascular access, which accounts for up to 20% of all hospitalization in HD patients. Studies to date on H-PF4 antibody and vascular access thrombosis in HD patients have produced conflicting data but have been limited by small sample sizes. We sough to determine the prevalence of H-PF4 antibodies in a large cohort of HD patients and the correlation with vascular access thrombosis.Pre-dialysis blood samples were drawn on 419 HD patients; 107 cases with access thrombosis and 312 controls that never had access thrombosis. H-PF4 antibodies were measured twice using an ELISA (GTI PF4 Enhanced, GTI Diagnostics). The average of the two measurements was used in this analysis. All patients received unfractionated heparin while on dialysis. The mean age was 64 16 yrs with 62% male patients. Antibodies to H-PF4 were positive in 54 (12.9%) patients. H-PF4 antibodies were present in 10 (10.5%) of patients with confirmed access thrombosis and in 44 (15.1%) of controls. Hemodialysis with repeated exposure to systemic unfractionated heparin is associated with a high prevalence of H-PF4 antibodies. Although H-PF4 antibodies contribute to hypercoagulability leading to thrombotic complications, our results are not supporting a correlation between H-PF4 antibodies and vascular access thrombosis. Given the potential for venous and arterial thrombosis and the implications of our findings further investigations are needed in this population.

Role of Genetic Factors in Vascular Access Thrombosis in Hemodialysis Patients

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.

The methylentetrahydrofolate reductase C677T point mutation is a risk factor for vascular access thrombosis in hemodialysis patients

Background: Many reports indicate that a high homocysteine (Hcy) level is a potential risk factor for such thrombotic diseases as arteriosclerosis, myocardial infarction, and cerebral infarction in healthy individuals or hemodialysis (HD) patients. The methylentetrahydrofolate reductase (MTHFR) C677T polymorphism has been reported to be closely related to plasma Hcy level. Methods: Using a cross-sectional design in this study, the relationship between arteriovenous fistula (AVF) obstruction and the MTHFR C677T point mutation was examined in 337 HD patients. Results: Results of multivariate analysis showed no significant influence of age, HD therapy duration, sex, or the presence of diabetes mellitus, cerebral infarction, or myocardial infarction. Only the presence of the MTHFR C677T polymorphism yielded a significant difference. Percentages of patients who experienced AVF obstruction were as follows: CC (12.6%), CT (20.3%), and TT (31.8%). The number of those who experienced obstruction was significantly larger with the TT than CC (P < 0.01). Moreover, total obstruction episode ratios were as follows: CC, 1 in 107.21 episodes/patient-month; CT, 1 in 74.08 episodes/patient-month; and TT, 1 in 50.33 episodes/patient-month. Episode percentages tended to be greater when the degree of mutation was greater, and a significant difference was observed between the CC and TT alleles (P < 0.01). Conclusion: Although AVF obstruction is affected by numerous factors, there was a strong relationship between MTHFR C677T mutation and AVF obstruction. These findings suggest that the MTHFR C677T point mutation could serve as an important indicator in identifying susceptibility to AVF obstruction. Am J Kidney Dis 41:637-642. © 2003 by the National Kidney Foundation, Inc.

Hyperhomocysteinemia, anticardiolipin antibody status, and risk for vascular access thrombosis in hemodialysis patients

Vascular access failure is an important cause of morbidity in end-stage renal failure patients on hemodialysis. Currently, little is known about risk factors that predispose certain hemodialysis patients to recurrent access thrombosis. Hyperhomocysteinemia (common in patients with renal failure) predisposes people with normal renal function to recurrent and early-onset venous thrombosis, although the effect on vascular access thrombosis is currently unknown. Previous studies have suggested that high titers of IgG anticardiolipin antibody (IgG-ACA) predispose hemodialysis patients to access thrombosis. This cross sectional study was designed to assess for an association between two predictive variables, hyperhomocysteinemia and elevated titers of IgG-ACA, and vascular access thrombosis in patients undergoing chronic hemodialysis. Risk factors for vascular access thrombosis were documented, and the number of episodes of access thrombosis was recorded for the previous three years in patients undergoing hemodialysis. Midweek predialysis total homocysteine and IgG-ACA levels were measured in all subjects. Of the 118 patients who were enrolled, 75.4% had a native arteriovenous fistula. Episodes of vascular access thrombosis were recorded for the previous three years; 34 (28.8%, 95% CI 20.9 to 37.9%) patients had 72 episodes of access thrombosis over the period of risk. Mean homocysteine levels were not significantly different between these 34 patients (28.6 micromol/liter, 95% CI 24.5 to 32.7) and the patients who had no episodes of graft thrombosis (29.8 micromol/liter, 95% CI 26.7 to 32.9). Sixty-seven unselected patients had IgG-ACA levels drawn for analysis, and all assays were negative. The only variable that was associated with a higher risk for graft thrombosis was the type of vascular access placed (odds ratio 4.0, 95% CI 1.6 to 9.6 for patients with a synthetic graft compared with those with an arteriovenous fistula). No association was found between homocysteine levels or anticardiolipin antibody and vascular access thrombosis in our patient population.