Hemostasis assessment with standard coagulation tests and rotational thromboelastometry (ROTEM) during therapeutic plasma exchange treatment.

AIMS: In therapeutic plasma exchange (TPE), large amounts of plasma with all components, including antibodies, albumin, coagulation factors and inhibitors, are removed and usually replaced with replacement fluid without coagulation factors. Hemostatic parameters should be closely monitored in patients at risk of bleeding or with large volume exchanges with a short recovery interval. In this prospective study, we compared standard coagulation parameters and the rotational thromboelastometry (ROTEM) point-of-care test to identify hemostatically severely compromised patients treated with TPE. MATERIALS AND METHODS: 22 patients without recent or planned invasive procedures received 63 TPE treatments with regional citrate anticoagulation. One plasma volume was exchanged with replacement fluid containing albumin and electrolytes. Standard coagulation tests, fibrinogen concentration, and rotational thromboelastometry (ROTEM, including EXTEM test, INTEM test, and FIBTEM test) were performed before and after each TPE treatment. RESULTS: Fibrinogen concentration decreased significantly and international normalized ratio increased slightly after TPE. Activated partial thromboplastin time, EXTEM, INTEM, and FIBTEM clotting times as well as clot formation times were prolonged, and maximum clot firmness decreased after TPE procedures. No serious adverse events occurred during TPE treatment. CONCLUSION: Our study showed that ROTEM parameters changed significantly after TPE performed with replacement fluid without coagulation factors. Among all parameters, FIBTEM clotting time showed the highest percentual change after TPE. According to this data, the ROTEM point-of-care test may have a potential to guide TPE therapy, particularly in patients at high risk for bleeding.

Bone mineral disturbances in patients with chronic kidney disease stage 5 not yet on dialysis.

AIMS: This retrospective study evaluates the success of a treatment strategy for secondary hyperparathyroidism in our cohort of patients with chronic kidney disease stage 5 who were not yet on dialysis. MATERIALS AND METHODS: 81 predialysis patients from the outpatient clinic of the Department of Nephrology, University Medical Center Ljubljana were reviewed. We focused on serum markers for bone mineral metabolism including intact parathyroid hormone (PTH), phosphate, corrected calcium, and the usage of phosphate-binding agents and vitamin D analogs. Results of intact PTH and phosphorus and calcium concentrations were related to treatment options for secondary hyperparathyroidism. RESULTS: The average intact PTH concentration was 198.8 ± 162.5 ng/L, serum phosphate was 1.52 ± 0.35 mmol/L, and corrected calcium was 2.23 ± 0.2 mmol/L. Phosphate-binding agents were prescribed in 62% patients, 44% of these patients were on calcium-containing phosphate binders. Active vitamin D or synthetic vitamin D analogs were given to 65% of patients, and 48% of all received a combination of active vitamin D derivate and inactive vitamin D supplementation. Serum intact PTH was between 150 and 300 ng/L in 30%, under 150 ng/L in 46%, and over 300 ng/L in 24% of patients, respectively. CONCLUSIONS: Our data show that 76% of our patients with CKD stage 5 not yet on dialysis achieved adequate control of secondary hyperparathyroidism. Marked reduction of intact PTH levels in a significant proportion of our patients prompt us to assess the administration of excessive amounts of calcium and/or vitamin D supplements to prevent over-suppression of PTH, which can induce adynamic bone disease.
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Citrate Extended High Cut-Off Hemodiafiltration for Renal Recovery in Patients With Multiple Myeloma.

We proposed a combination of convective and diffusive transport mechanisms as high cut-off (HCO) post-dilution hemodiafiltration dialysis technique to optimize serum immunoglobulin free light chains (FLCs) removal which may improve dialysis dependent renal failure in patients with multiple myeloma. To reduce bleeding risk regional citrate anticoagulation was successfully used for the first 7 h followed by 1 h anticoagulant-free hemodiafiltration to avoid citrate accumulation. We retrospectively assessed the effect of FLCs reduction on the renal outcome of 28 patients treated with 133 citrate extended post-dilution HCO (Theralite 2100; Gambro, Lund, Sweden) hemodiafiltration sessions between 2010 and 2016. Renal recovery was demonstrated in 61% of all patients. Twenty-three patients achieved more than 50% reduction of FLCs concentrations and 88% of those became dialysis independent. Our experience supports the extended citrate HCO hemodiafiltration as a good treatment strategy that enable a sustained reduction in serum FLCs concentration and recovery of renal function.

Malnutrition in Renal Failure: Pleiotropic Diagnostic Approaches, Inefficient Therapy and Bad Prognosis.

Malnutrition is very common and connected with high morbidity and mortality of patients on chronic hemodialysis. A cross-sectional, longitudinal study was performed in maintenance dialysis patients intending to determine association between modified Subjective Global Assessment (SGA), serum albumin and mortality. Cross-sectional study of phase angle (PhA) values and other indices of bioelectrical impedance body analysis (BIA) were correlated to biochemical data and malnutrition-inflammation score (MIS). In the group of 184 hemodialysis patients, we found 39 malnourished patients. In overall 50 months of observation, 25 out of 39 malnourished patients died. All patients with albumin values less than 30 g/L died. The group with albumin values greater than 30 g/L (N = 26) showed higher survival rate, 12 patients died in the observed period. SGA values higher than 21 and albumin values lower than 30 g/L are useful predictors of death in malnourished dialysis patients. PhA is an independent predictor of malnutrition with promising potential to replace other diagnostic tools.

Implementation of routine foot check in patients with diabetes on hemodialysis: associations with outcomes.

OBJECTIVE: Patients with diabetes are at increased risk of foot ulcers, which may result in limb amputations. While regular foot care prevents ulcerations and amputation in those patients with diabetes not on dialysis, evidence is limited in diabetic hemodialysis patients. We investigated the association between the implementation of a routine foot check program in diabetic incident hemodialysis patients, and major lower limb amputations. METHODS: In 1/2008, monthly intradialytic foot checks were implemented as part of standard clinic care in all Fresenius Medical Care North America hemodialysis facilities. Patients with diabetes who initiated hemodialysis between 1/2004 and 12/2007 constituted the preimplementation cohort, and patients starting hemodialysis between 1/2008 and 12/2011 comprised the postimplementation cohort. In addition, we conducted a sensitivity analysis where we excluded patients from the clinics with <10 patients in the postimplementation period and where percent difference in patient with diabetes number between postimplementation and preimplementation period was <20%. We compared lower limb amputation rates employing Poisson regression models with offset of exposure time in these two cohorts. RESULTS: We studied 35 513 patients in the preimplementation and 25 779 patients in the postimplementation cohort. In the postimplementation cohort, amputation rate decreased by 17% (p=0.0034). The major lower limb amputation rate was 1.30 per 100 patient years in preimplementation and 1.07 in postimplementation cohort. These beneficial results were corroborated in the multivariate analysis (p=0.0175) and were even more pronounced in the sensitivity analysis (p=0.0083). CONCLUSION: Monthly foot checks are associated with reduction of major lower limb amputations in diabetic incident hemodialysis patients.

Effect of switching to nocturnal thrice-weekly hemodialysis on clinical and laboratory parameters: our experience.

Long or frequent hemodialysis schedules are reported to improve clinical outcomes. We report here our experience with an in-center, nocturnal, thrice-weekly hemodialysis program. We retrospectively analyzed the effect of switching 10 patients (8 male, age 45 ± 11 years, renal replacement therapy vintage 12 ± 8 years) from regular, 4-5 h, thrice-weekly hemodialysis to 8 h nocturnal, in-center hemodialysis as regards dialysis efficiency, chronic kidney disease-metabolic and bone disease (CKD-MBD) parameters, blood pressure, and anemia. With more intense dialysis, the mean predialysis creatinine and urea decreased significantly (1092 ± 195 vs. 961 ± 154 µmol/L, P < 0.01 and 30.8 ± 4.6 vs. 25.5 ± 2.9 mmol/L, P < 0.01), while the decrease in potassium was insignificant (5.9 ± 0.7 vs. 5.6 ± 0.5 mmol/L), but in 3/10 patients, dialysate potassium was increased. Three months after starting nocturnal hemodialysis, no significant influence on pre-dialysis blood pressure was observed (143/80 vs. 140/80 mmHg), but antihypertensive medications were reduced in two patients. The mean dry weight reduced (74 ± 12 to 72 ± 12 kg) and the mean ultrafiltration increased insignificantly (3123 ± 1174 to 3434 ± 1341 mL). Serum calcium was stable, while phosphate reduced insignificantly (1.5 ± 0.5 to 1.2 ± 0.2 mmol/L), but 6/10 patients were able to discontinue phosphate binders, the dose was reduced in one, and phosphate was added to dialysate in 3/10 patients. Intact parathyroid hormone values were within the target range, except in patients post-parathyroidectomy. There were no differences in hemoglobin (121 ± 6 vs. 122 ± 8 g/L), and the mean epoetin dose decreased insignificantly (5950 ± 3947 vs. 5250 ± 4238 IU/week). To conclude, improved phosphate and potassium control and reduction in phosphate binders were observed after switching to nocturnal hemodialysis. There was an insignificant reduction of epoetin dose and antihypertensive medications.

Long-term citrate anticoagulation in chronic hemodialysis patients.

In some cases, long-term (>3 months) citrate anticoagulation is needed in maintenance hemodialysis patients due to a persistent bleeding risk. In this retrospective observational study, we present our experience and assess its safety and effects on mineral and bone disorder parameters. Sixteen patients (mean age 67 ± 15 years) were treated with long-term citrate anticoagulation. The indications were: recurrent gastrointestinal bleeding in nine patients, heparin-induced thrombocytopenia, retroperitoneal hematoma, chronic subdural hematoma, proliferative diabetic retinopathy, vascular malformations in the brain in one patient, and others in two patients. Metabolic complications and intact parathyroid hormone (iPTH) were analyzed. Citrate anticoagulation was performed for 4 months to 6.3 years (median 12 months). Ionized calcium was stable during the procedures; hypocalcemia (<0.9 mmol/L) was rare (2.1% of procedures), and there was one case of severe symptomatic hypocalcemia. There were no clinically significant acid-base disturbances and no clotting problems. In the short term (1-3 months after starting citrate), the iPTH increased in 73% of patients (from 325 ± 310 to 591 ± 793 pg/L, P = 0.11, N = 11). In the long term (1-2 years), an increase in iPTH was observed in 3/6 patients. The time period (before/after starting citrate) was a significant predictor of iPTH using main-effects anova (P < 0.001). To conclude, long-term citrate anticoagulation in chronic hemodialysis patients is safe. Mild hypocalcemia during dialysis with citrate anticoagulation may contribute to a short- and long-term increase in iPTH in these patients. Further studies on long-term citrate anticoagulation are necessary.

Guillain-Barré syndrome treated by membrane plasma exchange and/or immunoadsorption.

In this report, we evaluate the success of immunoadsorption and plasma membrane exchange treatment in patients with severe Guillain-Barré syndrome (GBS), and describe one case successfully treated by immunoadsorption after failure of plasma exchange therapy. Nineteen severely paralyzed GBS patients, aged 14-76 years, who were treated between 1998 and 2008, were retrospectively studied. They underwent 161 immunoadsorption and 119 plasma exchange procedures. In severe GBS, 4-30 immunoadsorption and 5-31 plasma exchange sessions were needed. Among 16 patients on mechanical ventilation, 11 recovered from disability completely, while in one patient mild muscle weakness persisted after one year. One patient suffered from ischemic stroke, two patients died after weaning from mechanical ventilation. One death was believed to be procedure-unrelated, the other patient died from sepsis. Four patients were lost to follow-up. We treated a 14-year-old, mechanically-ventilated patient using two different apheresis methods. After failure of 31 membrane plasma exchanges over 34 days, the patient was then switched to the immunoadsorption apheresis method, receiving seven sessions in 15 days. He no longer required assisted ventilation and recovered from the disability completely. A high number of immunoadsorption as well as membrane plasma exchange treatments can be safely and effectively applied in severe GBS patients. Our patients often needed, and were provided with, more than the currently arbitrarily accepted four apheresis sessions before good clinical recovery was achieved. For non-responders to plasma exchange treatment, immunoadsorption may be the first-line therapy.

Treatment of hyperlipidemic acute pancreatitis with plasma exchange: a single-center experience.

Of the cases of acute pancreatitis, 1-7% are caused by severe hypertriglyceridemia and can be treated with plasma exchange (PE). We report on a large series of patients with acute hyperlipidemic pancreatitis (HLP) treated with PE. In the 1992-2008 period, 50 patients (45 +/- 8 years old, 92% male) with acute HLP were treated with PE, during which 1-2 plasma volumes were exchanged. Heparin was used as anticoagulant in 85% of the procedures, and citrate in the rest. Cholesterol and triglycerides were measured before and after PE. In the 2003-2008 cohort of 40 patients, we retrospectively recorded an Acute Physiology and Chronic Health Evaluation II (APACHE II) score at the first PE session, hospital mortality, and length of hospital stay. A total of 79 PE treatments were done, 1-5 per patient. The volume exchanged was 4890 +/- 1300 mL over a duration of 3.5 +/- 2 h. During the first PE, the triglycerides were lowered from 58.9 +/- 40.8 to 10.8 +/- 10.8 mmol/L, and the total cholesterol was lowered from 20.0 +/- 7.6 to 5.7 +/- 4.3 mmol/L. In 10% of the procedures the plasmafilter was replaced, and in 3% the filter was clotted. Hypotension occurred in 3% of PE and there was one case of gastrointestinal bleeding after PE with heparin anticoagulation. In the 2003-2008 cohort, the median APACHE II score was 5 (range 0-15), the median overall hospital stay was 18 days (range 3-142 days) and the hospital mortality was 15%. To conclude, in acute hyperlipidemic pancreatitis, one to two plasma exchanges effectively reduce the serum triglyceride level. There is a low rate of procedure-related complications. A mortality rate of 15% is considerable.

Membrane plasma exchange for the treatment of thrombotic thrombocytopenic purpura.

The aim of our report is to present our 11-year experience with therapeutic membrane plasma exchange therapy for the treatment of idiopathic thrombotic thrombocytopenic purpura syndrome (TTP). In 56 patients, membrane plasma exchange therapy was initiated immediately and performed once or twice daily until the platelet count normalized. During each plasma exchange procedure, 1-1.5 plasma volumes (3606 +/- 991 mL) were replaced with fresh frozen plasma. In 37 females and 19 males (44 +/- 21 years), 1066 plasma exchange procedures were performed. The average duration of treatment was 23 +/- 17 days. The average number of plasma exchanges was 19 +/- 17 per patient. Renal impairment was detected in 36% of patients. At the initiation of plasma exchange treatment, the average platelet count was 31 +/- 30 x 10(9)/L and reached 199 +/- 95 x 10(9)/L thereafter. Fifty-two of 56 (93%) patients demonstrated an excellent response to plasma exchange therapy, of whom 48 patients (86%) attained complete remission with a platelet count of more than 100 x 10(9)/L. Four patients died soon after the initiation of plasma exchange therapy, when only 1-3 procedures had been performed. During the follow-up period, six patients with complete remission had 1-5 subsequent relapses each year. One of them died of acute hemolytic reaction during the tapering of plasma exchange procedures. Three patients underwent additional splenectomy. Our experience with primary TTP supports the plasma exchange treatment with fresh frozen plasma as a mandatory, up-to-date therapy. Close monitoring during all 1066 procedures showed no serious side-effects.

Hemodialysis catheters with citrate locking in critically ill patients with acute kidney injury treated with intermittent online hemofiltration or hemodialysis.

The purpose of the study was to compare the long-term catheter-related complications associated with temporary untunneled hemodialysis catheters, locked with citrate in the interdialysis period, inserted in critically ill patients with acute kidney injury, between different catheter insertion sites (femoral vs. jugular and subclavian) and catheter types (single-lumen [SL] vs. double-lumen [DL]). In a retrospective clinical study, the long-term catheter-related complications in 290 critically ill patients treated with intermittent high-volume online hemofiltration or hemodialysis between December 2004 and January 2008 were analyzed. Among 534 inserted catheters, 493 (92.3%) were femoral, 29 (5.4%) jugular, and 12 (2.3%) subclavian; 304 (56.9%) were SL and 230 (43.1%) were DL. There were 125 (20.3/1000 catheter days [c.d.]) thrombotic complications, while infectious complications were exceptionally rare, that is, only 13 (2.1/1000 c.d.), of which 10 (1.6/1000 c.d.) were possible catheter-related bloodstream infections and 3 (0.5/1000 c.d.) exit-site infections. The incidence rate of all thrombotic complications was significantly lower in all jugular and subclavian vs. all femoral catheters (7.7/1000 c.d. vs. 21.8/1000 c.d., P = 0.01), and in all SL vs. DL catheters (11.4/1000 c.d. vs. 32.2/1000 c.d., P < 0.001). The incidence rate of any possible catheter-related bloodstream and exit-site infections was not significantly different in all jugular and subclavian vs. all femoral catheters, neither in femoral SL vs. DL catheters. The major long-term catheter-related complications were thrombotic, and significantly more frequent in DL vs. SL catheters. Infectious complications were exceptionally rare, most probably due to the strict catheter care protocol, as well as the routine use of a citrate catheter lock and antibiotic ointment at the catheter exit-site.

Simultaneous determination of trace levels of ethylmercury and methylmercury in biological samples and vaccines using sodium tetra(n-propyl)borate as derivatizing agent.

Because of increasing awareness of the potential neurotoxicity of even low levels of organomercury compounds, analytical techniques are required for determination of low concentrations of ethylmercury (EtHg) and methylmercury (MeHg) in biological samples. An accurate and sensitive method has been developed for simultaneous determination of methylmercury and ethylmercury in vaccines and biological samples. MeHg and EtHg were isolated by acid leaching (H2SO4-KBr-CuSO4), extraction of MeHg and EtHg bromides into an organic solvent (CH2Cl2), then back-extraction into Milli-Q water. MeHg and EtHg bromides were derivatized with sodium tetrapropylborate (NaBPr4), collected at room temperature on Tenax, separated by isothermal gas chromatography (GC), pyrolysed, and detected by cold-vapour atomic fluorescence spectrometry (CV AFS). The repeatability of results from the method was approximately 5-10% for EtHg and 5-15% for MeHg. Detection limits achieved were 0.01 ng g-1 for EtHg and MeHg in blood, saliva, and vaccines and 5 ng g-1 for EtHg and MeHg in hair. The method presented has been shown to be suitable for determination of background levels of these contaminants in biological samples and can be used in studies related to the health effects of mercury and its species in man. This work illustrates the possibility of using hair and blood as potential biomarkers of exposure to thiomersal.

Increased ethyl mercury load in protein a immunoadsorption.

Immunoadsorption is an adsorption technique for extracorporeal removal of circulating autoantibodies in autoimmune diseases. To prevent microbial growth during storage, the protein A columns are primed with thiomersal, which contains toxic ethyl mercury, which may be released during the procedure and potentially begin to accumulate and become toxic. To reduce the thiomersal-related mercury release during immunoadsorption treatment, we introduced a modified rinsing solution containing N-acetylcysteine, which is an avid mercury scavenger. Thirteen patients received 17 protein A immunoadsorption treatments and their venous blood samples were collected immediately before and after each session. The total blood mercury levels were measured by atomic absorption spectrometry, and the ethyl mercury levels by atomic fluorescence spectrometry. Following the manufacturer's recommendations, we used 600 mg of N-acetylcysteine to rinse the mercury from protein-loaded columns before each immunoadsorption treatment. After immunoadsorption, the ethyl mercury levels increased from 0.148 +/- 0.402 ng/g to 2.026 +/- 1.944 ng/g (P < 0.001), and the total blood mercury levels increased from 2.447 +/- 3.065 ng/g to 20.437 +/- 28.603 ng/g (P = 0.02). The post-treatment values of total blood mercury exceeded the upper safety level of 5 ng/g in all 17 immunoadsorption treatments, but no patient developed clinical signs of mercury toxicity. The results of our study showed an increase in total blood mercury and ethyl mercury levels during the immunoadsorption treatments, suggesting mercury release from thiomersal-primed columns despite the addition of N-acetylcysteine to the rinsing solution.