Heparin-free Hemodialysis Research Articles

Hemodialysis without Systemic Anticoagulation: A Randomized Controlled Trial to Evaluate Five Strategies in Patients at a High Risk of Bleeding.

There has been growing interest in exploring combined interventions to achieve a more effective heparin-free treatment approach. to evaluate combination of interventions compared to standard practice (intermittent flushes) to prevent clotting and consequently reduce premature interruptions of hemodialysis. This open-label randomized controlled trial recruited chronic hemodialysis patients with contra-indication to systemic heparinization. Participants were randomized into one of five groups to receive different strategies of heparin-free hemodialysis treatment for up to three sessions. the successful completion of hemodialysis without clotting. the clotting of the air traps assessed by a semi-quantitative scale, online KT/V, and safety of the interventions. Forty participants were recruited and randomized between May and December 2020. Participants showed similar baseline biochemistry results and coagulation profiles. The highest success rates were observed in group 3 (heparin-coated dialyzers combined with intermittent flushes) (100%) and group 5 (hemodiafiltration with online predilution combined with heparin-coated dialyzers), with 91% vs. the control (intermittent flushes) (64%). Group 2 (heparin-coated dialyzers alone) had the poorest success rate, with 38% of the sessions being prematurely terminated due to clotting. KT/V and clotting scores were similar between groups. No adverse events related to the trial interventions were observed. The proposed combination of interventions may have had additive effects, leading to less frequent clotting and the premature termination of an HD/HDF session. Our study supports the feasibility of conducting a larger randomized controlled trial focusing on the efficacy of combined interventions for heparin-free HD in patients with a high risk of bleeding.

Safety and tolerability of the protein C activator AB002 in end-stage renal disease patients on hemodialysis: a randomized phase 2 trial

BackgroundThe protein C system regulates blood coagulation, inflammation, and vascular integrity. AB002 is an injectable protein C activating enzyme under investigation to safely prevent and treat thrombosis. In preclinical models, AB002 is antithrombotic, cytoprotective, and anti-inflammatory. Since prophylactic use of heparin is contraindicated during hemodialysis in some end-stage renal disease (ESRD) patients, we propose using AB002 as a short-acting alternative to safely limit blood loss due to clotting in the dialysis circuit.MethodsThis phase 2, randomized, double-blind, placebo-controlled, single-dose study evaluates the safety and tolerability of AB002 administered into the hemodialysis line of ESRD patients during hemodialysis at one study center in the United States (ClinicalTrials.gov: NCT03963895). In this study, 36 patients were sequentially enrolled into two cohorts and randomized to AB002 or placebo in a 2:1 ratio. In cohort 1, patients received 1.5 µg/kg AB002 (n = 12) or placebo (n = 6); in cohort 2, patients received 3 µg/kg AB002 (n = 12) or placebo (n = 6). Patients underwent five heparin-free hemodialysis sessions over 10 days and were dosed with AB002 or placebo during session four.ResultsHere we show that AB002 is safe and well-tolerated in ESRD patients, with no treatment-related adverse events. Clinically relevant bleeding did not occur in any patient, and the time to hemostasis at the vascular access sites is not affected by AB002.ConclusionsAs far as we are aware, this proof-of-concept study is the first clinical trial assessing the therapeutic potential of protein C activation. The results herein support additional investigation of AB002 to safely prevent and treat thrombosis in at-risk populations.

PREDICTORS OF UNFAVOURABLE OUTCOME IN PATIENTS ON MAINTENANCE HEMODIALYSIS WITH SARS COV 2 INFECTION

Introduction:The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was discovered in December 2019 in Wuhan, China, and quickly gave rise to a devastating pandemic. Due to uraemia-related immune system dysfunction, pro-inammatory state , higher comorbidity burden, and the potential of cross-contamination from dialysis centres; patients on maintenance haemodialysis appear to be particularly prone to SARS-CoV-2 infection. Materials and Methods The retrospective observational study aimed to determine the clinical, biochemical, pharmacological, and radiological prognosticators of favourable outcomes in patients on maintenance haemodialysis with COVID-19 infection. It included all adult patients who were on haemodialysis therapy and were admitted to B.M.H.Gimcare hospital, Kanuur , Kerala ; with a positive real-time reverse transcription-polymerase chain reaction for SARS-CoV-2 between September 2020 to February 2021, identied from the electronic medical records system. Result: The mean age of the study's 21 males and nine females was 61.47 years; of these patients, nine succumbed to their illness. The mean age of the deceased (67.11 ± 12.34 years), dialysis vintage period (31.67 ± 7.48 months), and duration of hospital stay (13 ± 8 days) were higher than those of the survivors (59.05 ± 11.42 years, 15.71 ± 7.24 months, and 8.67 ± 4.23 days, respectively). The TLC at admission (14033.33 ± 14423.07 per µL), N/L ratio (6.27 ± 6.38), and lactate dehydrogenase serum (457.11 ± 245.26) were also signicantly higher in those who had an unfavourable outcome. All cases on femoral dialysis access succumbed to this virus. Conclusion: We postulate that the outcome will be unfavourable in COVID-19 patients on heparin-free haemodialysis via femoral access, with higher total leukocyte levels, a raised neutrophil-lymphocyte ratio, lactate dehydrogenase and quick sequential organ failure assessment scores of more than two requiring invasive ventilatory support at admission.

A Phase 2 Trial of the Protein C Activator AB002 in End-Stage Renal Disease Patients on Chronic Hemodialysis

Background: During hemodialysis of patients with renal failure, thrombi that form within the dialyzer circuit cause blood entrapment, blood loss, reduced dialysis efficiency and may require dialyzer changeouts. Anticoagulation with heparin is effective in preventing clot formation within the circuit, but is contraindicated in a subset of end-stage renal disease (ESRD) patients on chronic hemodialysis due to bleeding risk or heparin intolerance. A safe, short-acting alternative to heparin is an unmet need for this patient population, and for others suffering from or at risk of thrombosis. AB002 is a first-in-class protein C activator thrombin analog that targets to the thrombus interface and generates endogenous activated protein C (APC) without cleaving prothrombotic substrates. In a preclinical baboon thrombosis model, AB002 rapidly interrupted thrombus development with no observable hemostasis impairment, and was similar in antithrombotic efficacy to high-dose enoxaparin while appearing superior to interventional tissue-plasminogen activator. This proof-of-concept phase 2 clinical trial was designed to evaluate the safety, tolerability, efficacy, and pharmacodynamics of AB002 as a heparin alternative for ESRD patients.Methods: In this phase 2, randomized, double-blind, placebo-controlled study, a single dose of AB002 (1.5 µg/kg or 3 µg/kg) or placebo was infused into the hemodialysis line over four hours in 36 ESRD patients undergoing heparin-free hemodialysis (NCT03963895). Patients underwent five sequential heparin-free hemodialysis sessions over a period of 10 days, with three occurring prior to dosing, one on the day of dosing, and one after dosing. A total of 179 hemodialysis sessions were evaluated. Safety parameters were recorded throughout the study and immunogenicity to AB002 or thrombin was monitored by validated assays. Clotting within the dialyzer circuit was visually assessed and the number of occlusive events requiring a changeout of the circuit recorded. Circulating plasma APC-protein C inhibitor complexes (APC-PCI) and thrombin-antithrombin (TAT) complexes, markers of drug exposure and thrombin generation, respectively, were quantified by ELISA. This study was approved by the local ethics review board and all patients provided informed consent.Results: AB002 demonstrated a favorable safety profile, with no treatment-related adverse events. Clinically relevant bleeding did not occur in any patient and the time to hemostasis at the vascular access site was not affected by AB002. There was no evidence of AB002-induced anti-drug or anti-thrombin antibodies at 14 days post-dose. The frequency of occlusive events requiring circuit changeouts was 13.9% (21/155) on days in which AB002 was not administered, compared to 0% (0/12) and 8.3% (1/12) at the 1.5 µg/kg and 3 µg/kg dose levels, respectively. Compared to placebo, the incidence of high-grade clotting in the hemodialyzer decreased by 49% and 62% at the 1.5 µg/kg and 3 µg/kg AB002 dose levels, respectively. Hemodialysis increased TAT levels measured at the end of hemodialysis approximately 12-fold over baseline in patients given placebo. By contrast, AB002 attenuated TAT generation to 4-fold and 2-fold over baseline at the 1.5 µg/kg and 3 µg/kg dose levels, respectively. Hemodialysis-induced TAT generation was not different across groups on non-dosing days. Drug exposure was confirmed by a transient, dose-dependent elevation of circulating APC-PCI complexes following AB002 administration.Conclusions: In ESRD patients undergoing heparin-free hemodialysis, AB002 was well-tolerated and reduced thrombus accumulation in the hemodialysis circuit without observable hemostasis impairment. The results of this study support further clinical evaluation of AB002 as a novel drug candidate to limit thrombus development or device-initiated clotting in patients with elevated bleeding risk, including ESRD patients on chronic heparin-free hemodialysis. DisclosuresVerbout: Aronora, Inc.: Current Employment. Lorentz: Aronora, Inc.: Current Employment. Markway: Aronora, Inc.: Current Employment. Wallisch: Aronora Inc,: Current Employment. Shatzel: Aronora Inc,: Consultancy. Gruber: Aronora Inc.: Current Employment, Current equity holder in publicly-traded company; Oregon Health and Science University: Current Employment.

Preparation of a heparin-like functionalized tannic acid-coated polyethersulfone ultrafiltration membrane for hemodialysis by a simple surface modification method

It is of practical significance to develop a heparin-free hemodialysis membrane that can be used for clinical applications in a simple way. In this work, a heparin-like coating loaded with SO3− and COOH was formed on a polyethersulfone (PES) ultrafiltration membrane by the hydrophobic interactions and hydrogen bonding of tannic acid (TA) with the PES membrane, the cross-linking of D-asparagine (DAS) with TA, and a Michael addition reaction of sodium 3-mercapto-1-propanesulfonic acid (SMP) with TA. The plasma recalcification time of the modified PES membrane was increased to 256 s, and the BSA rejection rate and urea clearance rate were 97.1% and 92.0%, respectively. The results demonstrated that a heparin-like tannic acid coating was successfully formed on the surface of the PES ultrafiltration membrane. The synergistic effect of the catechol and hydrophilic groups on the coating reduced platelet adhesion and activation, thus significantly improving the hemocompatibility modification of the PES membranes. Modified membranes with both high flux and excellent rejection (clearance) properties were also selected through the control of the coating. This study provides a novel and facile strategy for the direct preparation of a membrane material with excellent anti-hemagglutination properties.

The contact activation inhibitor AB023 in heparin-free hemodialysis: results of a randomized phase 2 clinical trial

AbstractEnd-stage renal disease (ESRD) patients on chronic hemodialysis have repeated blood exposure to artificial surfaces that can trigger clot formation within the hemodialysis circuit. Dialyzer clotting can lead to anemia despite erythropoietin and iron supplementation. Unfractionated heparin prevents clotting during hemodialysis, but it is not tolerated by all patients. Although heparin-free dialysis is performed, intradialytic blood entrapment can be problematic. To address this issue, we performed a randomized, double-blind, phase 2 study comparing AB023, a unique antibody that binds factor XI (FXI) and blocks its activation by activated FXII, but not by thrombin, to placebo in 24 patients with ESRD undergoing heparin-free hemodialysis. Patients were randomized to receive a single predialysis dose of AB023 (0.25 or 0.5 mg/kg) or placebo in a 2:1 ratio, and safety and preliminary efficacy were compared with placebo and observations made prior to dosing within each treatment arm. AB023 administration was not associated with impaired hemostasis or other drug-related adverse events. Occlusive events requiring hemodialysis circuit exchange were less frequent and levels of thrombin-antithrombin complexes and C-reactive protein were lower after AB023 administration compared with data collected prior to dosing. AB023 also reduced potassium and iron entrapment in the dialyzers, consistent with less blood accumulation within the dialyzers. We conclude that despite the small sample size, inhibition of contact activation–induced coagulation with AB023 was well tolerated and reduced clotting within the dialyzer. This trial was registered at www.clinicaltrials.gov as #NCT03612856.

MO657RANDOMIZED CONTROL TRIAL OF INTERMITTENT HEMODIALYSIS WITH REGIONAL CITRATE VS PRIMING HEPARIN WITH PREDILUTION IN PATIENTS AT RISK OF BLEEDING

Abstract Background and Aims Standard intermittent haemodialysis (SIHD) includes anticoagulation to avoid clotting of the dialysis system. In patients at high risk for bleeding, alternativ methods have been developed to avoid systemic anticoagulation. Regional citrate anticoagulation (RCA) is usually used with continuous renal replacement therapy and low blood flow but the Promotheus® device (Freseinus Medical care-Germany) allow RCA for liver support therapy with dialysis system 4008H® and blood flow over 200ml/min. The aim of this study was to compare the IHD with RCA (IHD-RCA) to SIHD without systemic anticoagulation in patients at high risk for bleeding. Method We conducted a randomized control trial study evaluating the superiority of IHD-RCA with Prometheus® device compared to SIHD with 5008H® dialysis monitor using priming heparin (5000UI unfractionated heparin) with predilution (25 ml/min) in a 4 hour IHD strategy in patients with high risk for bleeding. Randomization was stratified on vascular access. Sixty adult patients were randomly allocated to one IHD-RCA session or SIHD in a one ICU unit university center from 2019 to 2020. Bleeding risk was defined by nephrologist and inclusion need well-functioning fistula or double-lumen catheters with a protocol blood flow higher than 200 ml/min. The primary end point was the percentage of successful study period, defined as no premature interruption of a 4 hour hemodialysis session. Secondary end points included dialysis adequacy (KT/V), dialysis circuit bubble trap status and dialyzer membrane status by visual inspection. The study was declared in ClinicalTrial NCT03562754. Results Two patients from IHD-RCA were excluded of analysis because of early vascular access failure. Causes of bleeding risk were activ bleeding in 25(43%), recent surgery or organ biopsy in 31(53%) and Stroke in 2 sessions. 10(17%) patients were treated by IHD for AKI3 and other for chronic hemodialysis. 24(41%) patients have fistula, and the mean blood flow was significantly higher in SIDH group vs IHD-RCA (294 vs 263 ml/min, p<0.001). All sessions were performed with FX800 dialyzer (Polysulfone, hollow-filter 1.8M2, FMC). No statistically significant difference was observed for primary end point between group with 96% (27/28) of success for IHD-RCA and 83% (23/28) for SIHD (p=0.09). For secondary end point, no statistically significant difference was observed for KT/V delivery between group (1.69 vs 1.61, p=0.27) but score was statistically significant different between groups for visual inspection of fiber bundles (p<0.01) and dialysis circuit bubble traps aspect ( p<0.01 ) with higher score for SIHD. Conclusion No statitically significant difference was observed between 2 groups for 4-hour heparin-free hemodialysis sessions but we observed lower session failure with IHD-RCA. We confirm efficacy of Prometheus device for IHD-RCA in this population. Moreover, we report a low risk of 4-hour heparin-free session failure with SIHD without systemic anticoagulation using double lumen access, priming heparin, high blood flow, predilution and Polysulfone High-flux dialyser in comparison with other studies.

Safety and Efficacy of the Contact Activation Inhibitor AB023 in Patients with End-Stage Renal Disease on Chronic Hemodialysis: A Phase 2, Double-Blind, Randomized, Placebo-Controlled Trial

Background: End stage renal disease (ESRD) patients on chronic hemodialysis (HD) repeatedly have their blood exposed to artificial surfaces within the hemodialysis circuit, which triggers contact system-initiated coagulation. Clot formation within the HD circuit results in blood loss, decreased HD efficiency, and device circuit failure. Heparin reduces circuit clotting but it is not tolerated by all patients. Mounting experimental data suggest that contact system inhibition is antithrombotic without significantly compromising hemostasis. AB023 is a unique recombinant anti-factor (F) XI antibody that interferes with the interactions of FXI and FXII without inhibiting FXI activation by thrombin or the activation of FIX by activated FXI. This study evaluated the safety, tolerability, pharmacokinetics, and preliminary efficacy of AB023 in patients with ESRD on chronic HD. Methods: In this phase 2, randomized, double-blind, placebo-controlled, single-administration study, AB023 (0.25 or 0.5 mg/kg) or placebo was injected into the HD circuit of 24 ESRD patients at the start of heparin-free HD (NCT03612856). All patients underwent three pre-dose HD procedures and four monitored post-dose HD sessions. In total, the study encompassed 168 individual HD sessions, 72 of which occurred pre-dose and 96 of which occurred post-dose. Safety parameters, including time to hemostasis at HD access site, prothrombin time, physical examinations, vital signs, electrocardiograms, clinical chemistry, immunogenicity and other adverse events (AEs), were recorded. Clotting within the hemodialyzer circuit was assessed using a visual clotting scale by investigators who were blinded to treatment. The frequency of circuit clot obstructions requiring dialyzer exchange was also recorded. Pharmacokinetic and pharmacodynamic parameters, including activated partial thromboplastin times, were also assessed. The study was approved by an ethics review board and all subjects provided written informed consent. Results: AB023 demonstrated a favorable safety profile in ESRD patients. No drug-related AEs were noted. Clinically relevant bleeding did not occur in any patient, and the time to hemostasis at the HD access site was unchanged after AB023 administration. As expected, the aPTT was prolonged after AB023 administration, reaching saturation at both dose levels (about 2-fold prolongation) immediately after dosing, and remaining prolonged for up to 9 days with the high dose. Compared with pretreatment, the frequency of occlusive events requiring circuit exchange decreased by 68% and 50% in subjects given the 0.25 and 0.5 mg/kg AB023 respectively, while the number of occlusive events was numerically unchanged in the placebo arm. Likewise, the number of saline flushes required to maintain circuit patency decreased by 44% and 85%, and the incidence of high-grade clotting in the hemodialyzer as assessed by visual scoring decreased by 15% and 43% on day 1, 8% and 35% by day 3, and 0% and 19% by day 5 in the 0.25 and 0.5 mg/kg cohorts, respectively. Conclusions: Anticoagulation with AB023 was well-tolerated and reduced clot formation within the HD circuit of ESRD patients. These findings suggest that inhibiting contact system activation could reduce medical device-initiated blood clot formation in patients. Disclosures Lorentz: Aronora, Inc.: Current Employment. Verbout:Aronora, Inc.: Current Employment. Shatzel:Aronora, Inc.: Consultancy. Wallisch:Aronora, Inc.: Current Employment. Markway:Aronora, Inc.: Current Employment. Tucker:Aronora, Inc.: Current Employment. Gruber:Aronora, Inc.: Current Employment, Current equity holder in private company.

P1064HEPARIN-FREE DIALYSIS: A PHASE II PILOT STUDY USING ASYMMETRIC TRIACETATE (ATA) CELLULOSE DIALYZERS

Abstract Background and Aims Not all dialysis patients tolerate heparin anticoagulation. Heparin should be avoided in patients at high risk of bleeding. Strategies include saline infusion, citrate-containing dialysate, regional citrate anticoagulation and heparin-coated membranes. We recently studied the combination of a heparin-coated membrane and citrate-containing dialysate, with a success rate of 94% . Although this combination resulted in low rates of clotting, heparin-coated membranes are not ubiquitously available. The quest for easy to perform, safe and affordable heparin-free dialysis is on. Asymmetric cellulose triacetate (ATA) dialyzers have a low degree of platelet contact activation and might be an alternative to heparin-coated dialyzers. Method We performed a phase II pilot study in maintenance dialysis patients. The ‘Strategies for Asymmetrical Triacetate dialyzer heparin-Free Effective hemodialysis (SAFE study)’ was a two-arm open-label cross-over study. In Arm 1, patients were dialyzed using a 1.9 m2 ATA membrane (Solacea™-19H, Nipro Corp., Japan) in combination with citrate (1 mM) containing dialysate. In Arm 2, patients were dialyzed with the same 1.9 m2 ATA membrane, in combination with high volume predilution hemodiafiltration. The primary endpoint was the success rate to complete 4 hours of hemodialysis without preterm clotting. Results We scheduled 240 dialysis sessions (120 per arm) in twenty patients. Ten patients were randomized to start in Arm 1, the others to Arm 2. All patients crossed to the other arm halfway the study. 232 (96.7%) study treatments were delivered. Overall, 23 clotting events occurred, 7 in Arm 1 and 16 in Arm 2. Success rate in Arm 1 (ATA + citrate containing dialysate) was 90.8 / 94.0 % (intention to treat/ as treated). Success rate in Arm 2 (ATA + predilution HDF) was 83.3 / 86.2 % (intention to treat/ as treated). Therapy survival was borderline significantly better in Arm 1(Mantel-Cox log rank P = 0.05). Conclusion Asymmetric cellulose triacetate (ATA) dialyzers have a low clotting propensity. In combination with citrate-containing dialysate, asymmetric cellulose triacetate (ATA) may be a suitable alternative to heparin-coated membranes for systemic heparin-free hemodialysis.

Anticoagulant dialyzer with enhanced Ca2+ chelation and hydrophilicity for heparin free hemodialysis

Inhibiting thrombosis in extracorporeal dialyzer is predominantly determined by the compatible interface design. It is challenging to develop anticoagulant dialyzers for clinical heparin free dialysis. Herein, we develop an environmentally friendly approach to construct a hydrogel skin composed of poly (sodium alginate-acrylic acid) P (SA-AA) network on polysulfone (PSf) membranes via pre-seeding initiator into membrane matrix and subsequently crosslinking SA and AA in aqueous solution. Physicochemical properties of modified membranes with different SA/AA ratio were characterized by attenuated total reflectance fourier transform infrared spectra (ATR-FTIR) spectrum, proton nuclear magnetic resonance (13 C NMR), scanning electron microscopy (SEM) and atomic force microscope (AFM) and contact angle. Antifouling property was demonstrated by proteins adsorption and E. coli adhesion. Hemocompatibility was comprehensively evaluated by hemolysis ratio, anticoagulation activity (APTT and TT), complement activation, platelets activation and contact activation. Anticoagulant dialyzer was fabricated via skin implantation strategy to implement a chronic renal swine dialysis with heparin free administration. Clotting was significantly inhibited during the whole dialysis session, moreover, the dialyzer showed improved toxins clearance, including urea (~185 mL/min), creatine (~153 mL/min), inorganic phosphorous (~120 mL/min) and β2-microglobulin (~110 mL/min). The modified membrane bearing abundant carboxylate groups contributes to excellent hydrophilicity and Ca2+ chelation capability, which is considered to be the predominant anti-clotting mechanism via both intrinsic and extrinsic cascades. The anticoagulant PSf dialyzer demonstrates promising clinical application for heparin free dialysis.

Safety and Antithrombotic Efficacy of the Recombinant Protein C Activator AB002 (E-WE Thrombin) in End Stage Renal Disease Patients on Chronic Hemodialysis

AB002 is a recombinant thrombin analog that generates endogenous activated protein C (APC) on intravascular surfaces in a thrombomodulin-dependent manner but does not promote thrombosis. Endogenously generated APC downregulates thrombin generation, thereby reducing pathological clot formation. During hemodialysis (HD), thrombi can form within the dialyzer filter and circuit, reducing dialyzer efficiency, and increasing blood loss. Heparin administration reduces clotting within the filter and circuit, but increases bleeding risk and is not tolerated in all patients. Since end-stage renal disease (ESRD) patients undergoing HD are at higher risk of both thromboembolism and bleeding, a safe, short-term and self-limiting anticoagulant alternative to heparin is currently an unmet need for this population. This is a phase 2, randomized, double-blind, placebo-controlled, single-dose study designed to evaluate the safety and efficacy of AB002 at two dose levels when administered to ESRD patients during heparin-free HD. A total of 36 adult patients are planned to be enrolled into two cohorts and dosed sequentially. Within each cohort, patients will be randomized to active drug (12) or placebo (6). Dose levels (1.5 µg/kg or 3 µg/kg; iv infusion) were based on safety data from a completed phase 1 study performed in healthy adult subjects (NCT03453060), which demonstrated that a single dose of AB002 was well tolerated, as well as based on preclinical efficacy studies performed in a baboon vascular thrombosis model. The primary objective of this phase 2 proof-of-concept study is safety and tolerability assessed as the number and severity of adverse events (AE), changes in baseline physical and lab parameters and immunogenicity of AB002. The number and severity of AE will be tabulated and summary statistics evaluated. The secondary objectives are to assess 1) pharmacodynamics using activated protein C/protein C inhibitor complexes in plasma as a surrogate marker for drug exposure, and 2) efficacy via pre-post dialyzer pressures, visual inspection of thrombus accumulation in the HD filter and dialysis efficiency based on urea kinetics. The study population includes ESRD patients on a stable outpatient HD regimen at least 3 times per week and excludes patients with history of acute vaso-occlusive thrombotic events, concomitant use of anticoagulant/antiplatelet agents immediately prior to and during the study, active cancer and bleeding disorders. This study is currently recruiting participants at one study site (Orlando Clinical Research Center) in Orlando, FL and is estimated to complete in October 2020 (NCT03963895). Disclosures Verbout: Aronora, Inc.: Employment, Equity Ownership. Lorentz:Aronora, Inc.: Employment. Markway:Aronora, Inc.: Employment. Shatzel:Aronora, Inc.: Consultancy. Tucker:Aronora, Inc.: Employment, Equity Ownership. Gruber:Aronora, Inc.: Employment, Equity Ownership.

Design and application of an arterial circulation routes for hemodialysis without heparin

Objective To evaluate the effect of improved extracorporeal circulation blood route for prevention of complications in patients with chronic kidney disease (CKD) on hemodialysis. Methods A total of 80 cases of CKD patients were selected from June 2016 to June 2017.According to the random number table method, they were divided into the observation group and the control group, 40 cases of each group.The control group was treated with traditional one time hemodialysis pipeline during hemodialysis, while the observation group was treated with improved vascular access during hemodialysis.The complications and patient satisfaction during hemodialysis were compared between the two groups. Results The operation time, blood transfusion time and pre-punching time of observation group were shorter than those of the control group (P<0.05), the amount of saline of observation group was less than that of the control group (P<0.05). The amount of arterial backflow was higher than that of the control group (P<0.05). The incidence of adverse reactions such as coagulation, catheter related infection, circulating blood route exposure to air, oozing blood and arterial end prolapse in the observation group were lower than those in the control group(P<0.05). Degree of satisfaction in the observation group was higher than that of the control group(P<0.05). Conclusions Improved extracorporeal circulation blood route for heparin-free hemodialysis can effectively shorten the operation time of hemodialysis, reduce the incidence of coagulation in heparin-free hemodialysis apparatus and the risk of bloodstream infection, and the operation is safe and simple. Key words: Improved heparin-free hemodialysis; Extracorporeal circulation; Chronic kidney disease; Complication; Degree of satisfaction

Hemodialysis without anticoagulation: Less clotting in conventional hemodialysis than in predilution hemodiafiltration.

Hemodialysis patients with contraindication to systemic anticoagulation require a heparin-free hemodialysis technique. Among several alternatives to heparin, predilution hemodiafiltration (HDF) is often used, albeit without any confirmation of its effectiveness. Patients hospitalized in a nephrology ICU and hemodialysed for stage 5 CKD or AKI and with contraindication to systemic anticoagulation were randomized to either standard HD with a polysulfone membrane, or to predilution HDF with the same membrane. Coagulation activation was evaluated clinically by the need for premature termination and by the measurement of D-dimers. Two hundred dialysis sessions were performed in 155 patients. Survival curves showed better circuit survival in HD (P = 0.046). In HD, 12% of sessions were interrupted for coagulation versus 23% in predilution HDF (P = 0.04). Predilution HDF was associated with more premature clotting than conventional HD without improvement in dialysis duration or performance epuration indices. When aiming for a 4-hour duration session, conventional heparin-free hemodialysis can be safely proposed in most patients with high bleeding risk.

MON-124 CONTINUOUS SALINE INFUSION VERSUS INTERMITTENT SALINE FLUSHING IN PREVENTING CLOT FORMATION DURING HEPARIN-FREE HEMODIALYSIS

Heparin-free hemodialysis (HD) is a challenging procedure as it increases the risk of clotting in the extracorporeal circuit (ECC) which may lead to significant blood loss causing anemia necessitating blood transfusions, increasing doses of erythropoiesis-stimulating agents (ESAs) and iron supplements, thus adding to the burden of treatment cost. Although intermittent saline flushing (ISF) is a widely adopted method for the prevention of clotting during heparin-free hemodialysis, it is still sensible to find better techniques which can improve patient outcomes.

Evaluation with micro-CT of different anticoagulation strategies during hemodialysis in patients with thrombocytopenia: A randomized crossover study.

In patients with enhanced risk for bleeding, heparin-free hemodialysis (HD) with conventional dialyzers is routinely used. To explore the potential benefit of using heparin-coated dialyzers, we used a reference CT-scanning technique and registered different clotting parameters to quantify coagulation with heparin-coated versus non-coated dialyzers. Six HD patients with thrombocytopenia were dialyzed 240min in a randomized crossover study with Evodial 1.3 or FX600 Cordiax, each without anticoagulation. Blood samples were taken from the vascular access predialysis, and from the dialyzer inlet and outlet at 5 and 240min after dialysis start. Predialysis blood samples were analyzed for hemoglobin, hematocrit, thrombocytes, fibrinogen, and activated partial thromboplastin time. On dialyzer inlet and outlet blood samples, a viscoelastic measurement of blood coagulation was performed using a Sonoclot analyzer. After dialysis, dialyzers were visually scored, subsequently dried for 24h, weighed, and scanned with micro-CT at a resolution of 25µm. After image reconstruction, the open, non-coagulated fibers were counted in a representative cross-section at the dialyzer outlet. No sessions were terminated prematurely for circuit clotting. Heparin-coated dialyzers had more patent fibers on micro-CT versus non-coated dialyzers and also had a better score of subjective visual assessment of fiber clotting. There was no difference in subjective assessment of clotting at the venous drip chamber. With both dialyzers, all ACT values remained in the normal range, and were lower at the dialyzer outlet versus inlet. In conclusion, dialysis with a heparin-coated versus non heparin-coated membrane results in substantially less coagulated fibers during 4h hemodialysis without systemic anticoagulation. Eventual leaching of heparin, immobilized on the fiber membrane, does not result in measurable systemic anticoagulation.

Observation on the efficacy of vitrectomy for dialysis patients with end stage renal disease

Objective To observe the clinical efficacy of minimally invasive vitrectomy for dialysis patients with end stage renal disease(ESRD). Methods The clinical data of 21 eyes of 18 dialysis patients with ESRD, who underwent minimally invasive vitrectomy due to proliferative diabetic retinopathy or vitreous hemorrhage were retrospectively reviewed. Six eyes of 5 cases were treated with peritoneal dialysis and 15 eyes of 13 cases were received heparin-free hemodialysis. The visual acuity, intraocular pressure and complications intraoperative and postoperative were observed in two groups. Results The postoperative visual acuity improved in two groups(t=2.589, P=0.018). The difference of intraocular pressure was not statistically significant between before and after surgery (t=-0.476, P=0.639). The difference of visual acuity, intraocular pressure and the rate of intraoperative and postoperative complications were not statistically significant between two groups (P>0.05). Preoperative intravitreal ranibizumab injection had no influence on complications, surgery time and final visual acuity. Conclusion Minimally invasive vitrectomy can improve the final visual acuity and achieve retinal reattachment for dialysis patients with ESRD, who suffering from vitreous hemorrhage or proliferative diabetic retinopathy. Compared with peritoneal dialysis, heparin-free hemodilysis is unlikely to increase the risk of intra and postoperative complications. Key words: Renal disease, end stage, dialysis; Vitrectomy

Heparin-free renal replacement therapy for chronic hemodialyzed patients at high risk for bleeding: a comparison of on-line predilution hemodiafiltration with conventional hemodialysis.

In chronic hemodialysis patients with high risk of bleeding, optimal anticoagulation of the extracorporeal circuit is challenging. Heparin-free hemodialysis (HD) with heparin-coated AN69ST dialyzer is now considered as a good option and recommended by experts. Predilutional hemodiafiltration (HDF) may represent also a feasible alternative but has been poorly investigated. In this study, our aim was to evaluate the performance of on-line automated predilution heparin-free HDF as compared to conventional heparin-free HD with a heparin-coated membrane. We prospectively studied chronic hemodialysis patients at high risk of bleeding consecutively admitted to hospital who underwent heparin-free renal replacement therapy (RRT) in our nephrology department. During 1 year, we routinely used heparin-free HD and on-line HDF in these settings. By using a propensity score, we compared HDF to HD regarding to session failure and efficiency. One hundred and seventy-nine patients were included in the study. Clotting phenomena necessitating premature termination of RRT sessions were encountered in 19% of them. After propensity score matching, the comparison of 77 HD and 77 HDF sessions showed no significant differences in duration of the sessions and in dialyzer clotting. By multivariate analysis, a blood flow less than 250 mL/min and recent surgery were the only parameters associated with extracorporeal circuit thrombosis. Heparin-free on-line predilutional HDF is a safe and effective technique for chronic hemodialysis patients with increased bleeding risk. The use of an automatic substitution volume that avoids filters hemoconcentration and of a blood flow above 250 mL/min strongly contribute to the observed performance. Further studies are, however, intended to confirm these results.

Simple citrate anticoagulation protocol for low flux haemodialysis

BackgroundFor patients unable to receive heparin anticoagulation during haemodialysis, saline flushes to reduce circuit clotting are often the norm. Regional citrate anticoagulation (RCA) although effective is not used by many centres including in Singapore. We wanted to demonstrate the superiority and safety of a simple regional citrate anticoagulation regime, compared to saline flushes, for heparin-free low flux haemodialysis.MethodsThis is a prospective, open label, cross over study on 25 sequential haemodialysis sessions for inpatients receiving heparin-free haemodialysis. Patients were allocated either to regional citrate anticoagulation or standard heparin free haemodialysis and subsequently cross over to the alternate method. RCA was carried out using a protocol derived from previous studies. Assessment of anticoagulation was performed using visual inspection of clot formation in dialysis circuits and post-filter ionized calcium (iCa2+) using point-of-care Ionized calcium device at stipulated intervals. Intravenous Calcium gluconate replacement was given to patients receiving citrate adjusting the rate according to pre-filter iCa2+. Laboratory analyses of electrolytes were also assessed at the start and end of the RCA sessions.ResultsThere were no clots in the RCA arm, with 79% (n = 19) in the saline flush arm having some clot, including 1 clotted circuit. Post-filter iCa2+ at various time points were within acceptable range.Electrolyte readings in the RCA group were all within normal limits except for 4 cases of total Calcium:iCa2+ ratio > 2.5.ConclusionRCA is confirmed to be superior to saline flushes for circuit patency. We have a simple and safe protocol that can be followed for low flux haemodialysis.The study was approved by Singapore National Health Group domain-specific ethnical committee. NHG DSRB reference number 2014/01037.Trial registrationTrial registration number: ISRCTN69952745 (registration date 8/11/17).

Anesthetic management of primary hyperparathyroidism during pregnancy

Rationale:Primary hyperparathyroidism (PHPT) during pregnancy is rare. Nevertheless, hypercalcemia secondary to gestational PHPT may be masked by physiological changes in calcium homeostasis during pregnancy. Gestational PHPT constitutes a serious danger to mother and fetus. Surgery is the only curative treatment when conservative treatment could not control the condition. Due to the lack of guidelines concerning PHPT during pregnancy, the optimal anesthetic management of PHPT during pregnancy needs to be individualized. Patient concerns: We report a case of PHPT with successful surgical treatment under combined cervical plexus block and general anesthesia.Diagnosis:She was diagnosed with hypercalcemia, PHPT, a possible parathyroid adenoma, and a 19-week intrauterine pregnancy.Interventions:The patient underwent heparin-free hemodialysis before the surgery in the nephrology department in the presence of a cardiologist. She then received a successful parathyroidectomy under combined bilateral superficial cervical plexus block and general anesthesia in her 19th week of pregnancy.Outcomes:She was released from the hospital with no maternal or fetal complications on postoperative day 9. A healthy baby boy was uneventfully born at 37 weeks of gestation.Lessons:We suggest that surgical removal of the lesion after lowering the blood calcium concentration in mid-pregnancy is currently the optimal treatment option for pregnant patients with PHPT. Furthermore, multidisciplinary perioperative management is particularly important.

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.