The anticoagulant activity of enoxaparin sodium during on-line hemodiafiltration and conventional hemodialysis

To study and compare the anticoagulant activity of enoxaparin sodium during on-line hemodiafiltration (OL-HDF) and conventional hemodialysis (C-HD). Enoxaparin was administered as an anticoagulant to 21 hemodialysis patients at the beginning of a single 4-hour OL-HDF session as an intravenous bolus dose of 80 mg/kg. On-line hemodiafiltration was performed using a high-flux polyester polymer alloy dialyzer and a total of 18 L replacement fluid (session A). One week later, the study was repeated in the same patients during a single 4-hour session of C-HD using a low-flux polysulfone dialyzer (session B). Blood samples for the measurement of Hb, blood urea and nitrogen (BUN), activated partial thromboplastin time (APTT), and anti-Xa levels were taken before each study session and 5-minute postdialysis. In 13 more patients, the same study was performed during OL-HDF using a high-flux polysulfone dialyzer (session C). No differences were found between sessions A, B, and C when predialysis values for Hb, BUN, APTT, and anti-Xa were compared. The mean postdialysis APTT and anti-Xa values were 32.5±3.8 seconds and 0.19±0.11 IU/mL, respectively, in session A, 39.0±5.0 seconds and 0.71±0.17 IU/mL in session B, and 33.8±3.1 seconds and 0.35±17 IU/mL in session C (A vs. B, P<0.0001, for both parameters, A vs. C, P<0.003 for anti-XA, and B vs. C, P<0.005, for both parameters). The anticoagulant activity of enoxaparin sodium is decreased significantly during a 4-hour OL-HDF session compared with to a similar session of C-HD. The degree of the reduction seems to depend on the dialyzer's membrane.     

Plasma myeloperoxidase,NT‐proBNP,and troponin‐I in patients on CAPD compared with those on regular hemodialysis

Myeloperoxidase (MPO) is a hemoprotein that is released during inflammation and may lead to irreversible protein and lipid modification, increasing levels of oxidized low density lipoprotein, and promoting athrogenesis. Recently, it has been considered as a risk factor for cardiovascular diseases. Similarly, the measurement of carotid intima‐media thickness gives an indication about the degree of atherosclerosis and prediction of clinical cardiovascular events. Elevated white blood cells counts may indicate a state of acute inflammation and follow its progression. Dialysis patients are at a high risk of developing cardiovascular disease compared with healthy subjects. The role of N‐terminal pro‐brain natriuretic peptide and increased cardiac troponin in identification and prognostication of cardiovascular diseases in end‐stage renal disease patients has been investigated. The current study aimed to evaluate plasma MPO and its possible relationship with carotid intima‐media thickness, troponin I, N‐terminal pro‐brain natriuretic peptide (NT‐proBNP), and insulin resistance as measured by homeostatic model assessment (HOMA index) in a cohort of Saudi patients who are undergoing hemodialysis (HD) vs. continuous ambulatory peritoneal dialysis for end‐stage renal disease. Plasma MPO was significantly higher in patients on continuous ambulatory peritoneal dialysis (CAPD) than in those on HD and in normal subjects (P<0.001). Conversely, NT‐proBNP plasma levels were significantly higher in patients on HD (both predialysis and postdialysis) than in those on CAPD (P<0.01) and than normal subjects. Similarly, plasma troponin‐I levels were significantly higher in patients on HD compared with those of CAPD and than normal subjects (P<0.001). Plasma troponin‐I and NT‐proBNP levels were positively correlated in the 3 groups namely those on CAPD, Pre‐HD, and post‐HD (r: 0.464 and P=0.047; r: 0.330 and P=0.013; and r: 0.452 and P=0.024), respectively. There was no correlation between the MPO level and carotid intima‐media thickness (P>0.05). However, plasma MPO level correlated positively with the white blood cell count in patients on CAPD and in those on HD (P<0.05). Our findings suggest an increased oxidative stress in CAPD patients compared with HD patients, while the reported difference in plasma NT‐proBNP and troponin‐I may be related to the rapid decline of residual renal function in HD and type of membrane used in the HD dialysis procedure itself.     

Dialysis‐associated allergic reactions during continuous renal replacement therapy and hemodialysis: A case report

Dialyzer reactions are long‐appreciated complications of dialysis. Despite advances in dialysis machines and membranes, these life‐threatening reactions still occur. It is imperative to recognize potential dialyzer reactions when assessing adverse dialysis events as reexposure to dialytic treatments could be life threatening. We present the case of a 72‐year old woman with dialysis‐requiring anuric acute kidney injury who experienced acute hypotension and cardiopulmonary arrest during both continuous renal replacement therapy and a subsequent hemodialysis treatment. We concluded that she had an anaphylactic reaction to an unidentified component of the dialysis equipment. Identification, work up, treatment, and reporting of dialyzer reactions are discussed in the context of this case.     

Heparin‐grafted dialysis membrane allows minimal systemic anticoagulation in regular hemodialysis patients: A prospective proof‐of‐concept study

This prospective, multicenter, proof‐of‐concept study aimed to evaluate the possibility to reduce the ordinary heparin dose and the systemic anti‐Xa activity during hemodialysis (HD) sessions using a new heparin‐grafted HD membrane. In 45 stable HD patients, the use of a heparin‐grafted membrane with the ordinary heparin dose was followed by a stepwise weekly reduction of dose. Reduction was stopped when early signs of clotting (venous pressure, quality of rinse‐back) occurred during two out of three weekly HD sessions. Heparin dose was decreased for 67% of patients resulting in the lowering of these patients' anti‐Xa activity by 50%. Dose reductions were achieved with both types of heparin (low‐molecular‐weight heparin: 64 ± 14 to 35 ± 12 IU/kg, P < 0.0001; unfractionated heparin: 82 ± 18 to 46 ± 13 IU/kg, P < 0.0001) resulting in a decrease of anti‐Xa activity at dialysis session end (low‐molecular‐weight heparin: 0.51 ± 0.25 to 0.25 ± 0.11 IU/mL, P < 0.0001; unfractionated heparin: 0.28 ± 0.23 to 0.13 ± 0.07 IU/mL, P < 0.0001). Failure to further decrease heparin dose was related to signs of clotting in blood lines (57% of sessions), in dialyzer (9%), or both (34%). Significant reduction of heparin dose and anti‐Xa activity at the end of HD sessions was possible in stable HD patients using heparin‐grafted membrane. HD patients who require low anti‐Xa activity at the end of HD sessions might benefit from a heparin‐grafted membrane to reduce bleeding risk and other heparin adverse events.     

Predictive value of serum myeloperoxidase activity for thrombosis of arteriovenous fistulas

Myeloperoxidase is a proinflammatory protein that appears as a result of increased oxidative stress. It plays an important role in the promotion and progression of atherosclerosis. The aim of this study was to determine the importance of MPO as a predictive parameter for thrombosis of arteriovenous fistula (AVF). The study involved monitoring patients with AVFs for hemodialysis over a period of 2 years. There were 41 patients, 19 (46%) men and 22 (54%) women, with mean age of 65 ± 12.7 years. Routine laboratory analyses were carried out in all respondents, including determination of MPO concentration. Gender, demographic and anthropometrical characteristics, smoking, alcohol consumption, as well as the presence of diabetic nephropathy, as an etiological factor of kidney disease, were recorded. The group of patients who developed initial thrombosis of the AVFs had significantly different values for leukocytes (8.5 ± 3.8 vs. 7.3 ± 2.1, P = 0.024), erythrocytes (2.8 ± 0.27 vs. 3.2 ± 0.65; P = 0.019), hemoglobin (88.5 ± 81 vs. 99.1 ± 6.02; P = 0.041), and myeloperoxidase (19.3 ± 4.67 vs. 11.1 ± 4.43; P = 0.007) when compared with the group without fistula thrombosis. Diabetic nephropathy (P = 0.02) characterized the group of patients with thrombosis of the fistula. Diabetic nephropathy (B = 2.53, P = 0.049) and MPO (B = 0.03, P = 0.029) were statistically significant predictors of fistula thrombosis. In our study, MPO and diabetic nephropathy were predictors of thrombosis of the AVF.     

Effects of frequent hemodialysis on blood pressure: Results from the randomized frequent hemodialysis network trials

Hypertension is a common complication of chronic kidney disease and persists among most patients with end‐stage renal disease despite the provision of conventional thrice weekly hemodialysis (HD). We analyzed the effects of frequent HD on blood pressure in the randomized controlled Frequent Hemodialysis Network trials. The daily trial randomized 245 patients to 12 months of 6× (“frequent”) vs. 3× (“conventional”) weekly in‐center hemodialysis; the nocturnal trial randomized 87 patients to 12 months of 6× weekly nocturnal HD vs. 3× weekly predominantly home‐based hemodialysis. In the daily trial, compared with 3× weekly HD, 2 months of frequent HD lowered predialysis systolic blood pressure by ?7.7 mmHg [95% confidence interval (CI): ?11.9 to ?3.5] and diastolic blood pressure by ?3.9 mmHg [95% CI: ?6.5 to ?1.3]. In the nocturnal trial, compared with 3× weekly HD, 2 months of frequent HD lowered systolic blood pressure by ?7.3 mmHg [95% CI: ?14.2 to ?0.3] and diastolic blood pressure by ?4.2 mmHg [95% CI: ?8.3 to ?0.1]. In both trials, blood pressure treatment effects were sustained until month 12. Frequent HD resulted in significantly fewer antihypertensive medications (daily: ?0.36 medications [95% CI: ?0.65 to ?0.08]; nocturnal: ?0.44 mediations [95% CI: ?0.89 to ?0.03]). In the daily trial, the relative risk per dialysis session for intradialytic hypotension was lower with 6×/week HD but given the higher number of sessions per week, there was a higher relative risk for intradialytic hypotensive requiring saline administration. In summary, frequent HD reduces blood pressure and the number of prescribed antihypertensive medications.     

Assessing the contact‐activation of coagulation during hemodialysis with three different polysulfone filters: A prospective randomized cross‐over trial

Introduction: During hemodialysis (HD) the interaction of the blood with the dialyzer triggers both an inflammatory reaction and an activation of the coagulation cascade. An accepted parameter to quantify the extent of coagulation activation during HD is not available. This study aims to evaluate its amplitude, comparing dialyzers made of different polysulfone polymers, by measuring D‐dimers in the filter‐rinsing fluids (Frf) and to test whether Frf D‐dimers are suitable candidate markers to assess contact coagulation activation during HD. Methods: In a prospective, cross‐over study 41 hemodialysis patients were randomly allocated to nine HD sessions with three types of polysulfone membranes: Filter A: Poliflux®RevaclearMAX; Filter B: Helixone®Fx80, Filter C: Polyflux®H210. Findings: A total of 117 HD sessions were studied. The mean (SD) filter (Frf) D‐dimers were 0.19 µg/L (0.56) for Filter A; 0.66 µg/L (2.81) for Filter B; 0.33 µg/L (1.13) for Filter C. Significant differences were found: A vs. B (P < 0.01), A vs. C (P = 0.01); B vs. C not significant. A large between‐patient variability of D‐dimer filter levels was found. D‐Dimers in blood showed a similar trend but differences were not significant. Discussion: The contact activation of coagulation during HD may also vary among filters made up with similar polysulfones. D‐dimer in the filter rinsing fluid but not in the blood can be considered a candidate marker for the evaluation of thrombogenicity during HD. Further studies are needed to elucidate the mechanism(s) and to confirm the usefulness of filter rinsing fluid D‐Dimers as a clotting activation marker during HD.     

Effects of music on complications during hemodialysis for chronic renal failure patients

The study was planned as a case‐control study to examine the effects of music on some of the complications experienced by chronic renal failure (CRF) patients during hemodialysis. A total of 60 patients (30 intervention and 30 control) diagnosed with end‐stage renal failure undergoing hemodialysis treatment participated in this study. The study was conducted in Manisa Merkez Efendi State Hospital Hemodialysis Unit and Manisa Özel Anemon Hemodialysis between April 2012 and July 2012. The intervention group listened 30 minutes in each session (12 total sessions) Turkish art music at the beginning of the third hour of their hemodialysis sessions. Patient Information Form and visual analog scale to assess pain, nausea, vomiting, and cramps during hemodialysis session were used. For the analysis of data, the number, percentage, chi‐square test, and significance test of independent group differences between two averages were conducted. According to the findings of the study, the average of the intervention and control group ages, respectively, was 50.86 ± 11.3 and 55.13 ± 9.68. The primary duration of hemodialysis treatment for both intervention and control groups was “1 year and above” (70.0%). The intervention group's pain and nausea scores were lower than the control group for all 12 sessions. The difference between the intervention and the control group's pain scores was significant (P < 0.05). However, in pain scores from the first session to 12th session, continuous decreasing trend was not observed. According to the results, music can be used as an independent nursing practice for reduction of complications for CRF patients receiving hemodialysis treatment.     

Clinical consequences of heparin-free hemodialysis

Heparin-free hemodialysis (HF-HD) has been increasingly used in patients at risk for bleeding, especially in the intensive care unit (ICU). Lack of heparin can reduce solute clearances in continuous hemofiltration; the effect on HD is undefined. Failure to recognize an effect of the anticoagulation strategy upon delivered clearance could contribute to the known problem of underdialysis in the ICU. In addition, the consequences of "locking" dialysis catheters with concentrated heparin solutions are also unclear. This study was designed to define the clinically relevant consequences of HF-HD and catheter locking. In part I, we performed 200 HD treatments on inpatients, of which 100 were performed with heparin, and 100 were performed as HF-HD. We calculated prescribed and delivered Kt/V and dialysis efficiency. In part II, a separate group of 14 patients undergoing HF-HD via central venous catheters had measurement of activated partial thromboplastin time (aPTT) during the last hour of dialysis, as well as 15, 60, and 240 min after catheters were locked with 1:5000 heparin. The prescribed Kt/V was 1.74+/-0.31 for standard HD with heparin vs. 1.66+/-0.36 for HF-HD (p=ns). The delivered Kt/V was 1.42+/-0.32 vs. 1.36+/-0.38 (p=ns). Efficiency was 0.82 vs. 0.84 (p=ns). Baseline aPTT was 28+/-5 s, and increased to 126+/-54 s, 15 min after locking (p<0.0001) and to 71+/-50 s, 60 min after locking (p=0.005). By 240 min, the mean aPTT had fallen to 33+/-9 s (p=0.03), although individual values were still as high as 50 s. The HF technique does not compromise delivery of dialysis to inpatients. Increased treatment time is not necessary. Locking catheters with heparin after HF-HD resulted in prolonged unintentional anticoagulation.     

A case of anaphylactic shock induced by FX60 polysulfone hemodialyzer but not F6‐HPS polysulfone hemodialyzer

A 75‐year‐old woman was admitted for dyspnea and fever. She underwent emergent dialysis smoothly under F6‐HPS polysulfone hemodialyzer. With two subsequent hemodialysis sessions, severe anaphylactic reaction with cardiopulmonary resuscitation occurred under FX60 polysulfone dialyzer. Further dialysis sessions by F6‐HPS polysulfone dialyzer were uneventful. This rare case demonstrated that dialyzer reaction may be markedly different even with the same material and the same manufacturer.     

Heparin albumin priming in a clinical setting for hemodialysis patients at risk for bleeding

Introduction: Intermittent hemodialysis (IHD) is sometimes necessary in patients with a bleeding risk, i.e., before/after surgery or brain hemorrhage. In such case IHD has to be modified to limit the conventional anticoagulation used to avoid clotting of the extracorporeal circuit (ECC). We evaluated if priming using a heparin and albumin (HA) mixture could minimize the exposure to heparin. Methods: Retrospective data from 1995 to 2013 were collected from 1408 acute dialysis treatment protocols that included 321 patients. Comparisons were made between IHD patients that had increased risk for bleeding and were treated by standard anticoagulation (Group‐S), and patients at increased risk of bleeding (Group‐HA). The ECC in Group‐HA was primed with a solution of unfractioned heparin (UFH) (5000 Units/L) and albumin (1 g/L) in saline that was discarded after priming. There were 16 different dialyzers in the material. Findings: Comparing Group‐S (n = 883) with Group‐HA (n = 221), the mean age was 61.6 vs. 62.2 years (P = 0.8), dialysis time was 197 vs. 190 minutes (P = 0.002), and total dose of intravenous anticoagulant/IHD was at median 5000 Units vs. 1200 Units (P = 0.001). Twenty‐four percent of patients were treated without any additional heparin. Clotting resulting in interrupted dialysis was similar in both groups (0.8% for Group‐S vs. 1.0% for Group‐HA, P = 0.8). No secondary bleeding was reported in either group. Discussion: HA priming minimized the risk of clotting and enabled acute IHD in vulnerable patients without increased bleeding, thus allowing completion of IHD to the same extent as for standard HD.     

Heparin leak from a hemodialysis catheter causing major bleeding,ultimately leading to transplant rejection and death

Leakage of hemodialysis catheter‐locking solutions into the circulation has been reported in in vitro and in vivo studies, although there have been few reports of serious clinical adverse events. We describe a case of heparin leak from a hemodialysis catheter, which caused significant clinical bleeding requiring multiple transfusions and may have ultimately been responsible for the patient's death after transplantation.     

Recurrent heparin‐induced thrombocytopenia due to heparin rinsing before priming the machine in a hemodialysis patient: A case report

Heparin has remained the most commonly used anticoagulant for patients undergoing hemodialysis. It is usually safe to use but can have severe adverse effects in some cases. Heparin‐induced thrombocytopenia (HIT) is a life‐threatening complication of exposure to heparin. It results from an autoantibody directed against endogenous platelet factor 4 (PF4) in complex with heparin, which activates platelets and can cause catastrophic arterial and venous thromboses. Here, we present the case of an 80‐year‐old woman with a recent diagnosis of chronic renal failure who developed acute HIT (platelet count nadir, 15 × 10⁹/L) on day 7 of hemodialysis performed with routine heparin anticoagulation, who despite subsequent heparin‐free hemodialysis (with argatroban and warfarin) developed recurrent HIT (complicated by acute cerebral infarction) on day 11 that we attributed to “rinsing” of the circuit with heparin‐containing saline (3,000 units of unfractionated heparin, with subsequent saline washing) performed pre‐dialysis as per routine. After stopping heparin rinsing, the platelet count recovered completely, without further thrombotic or other sequelae. Our experience indicates that for patients with acute HIT, besides the well‐known practice of using non‐heparin anticoagulation during dialysis and avoiding heparin “locking” of dialysis catheters, it is also important to avoid inadvertent rinsing of the circuit with heparin during preparation for hemodialysis.