An evaluation of four modes of low-dose anticoagulation during intermittent haemodialysis

European Journal of Clinical Pharmacology https://doi.org/10.1007/s00228-017-2389-x CLINICAL TRIAL An evaluation of four modes of low-dose anticoagulation during intermittent haemodialysis Malin S. E. Skagerlind 1,2 & Bernd G. Stegmayr 1 Received: 7 October 2017 / Accepted: 26 November 2017 # The Author(s) 2017. This article is an open access publication Abstract Introduction Intensive care participants that need dialysis frequently suffer from increased risk of bleeding. Standard intermittent haemodialysis (SHD) includes anticoagulation to avoid clotting of the dialysis system. The aim of this study was to clarify which of four different low-dose anticoagulant modes was preferable in reducing the exposure to i.v. unfractionated heparin (heparin) and maintaining patency of the dialysis circuit. Methods Twenty-three patients on SHD were included to perform haemodialysis with four modes of low-dose anticoagulation. For comparative analyses, patients served as their own control. Haemodialysis with a single bolus of tinzaparin at the start was compared to haemodialysis initiated without i.v. heparin but priming with (1) heparin in saline (H), (2) heparin and albumin in saline (HA), (3) heparin and albumin in combination with a citrate-containing dialysate (HAC), (4) saline and usinga heparincoated filters (Evodial®). The priming fluid was discarded before dialysis started. Blood samples were collected at 0, 30 and 180 min during haemodialysis. Smaller bolus doses of heparin (500 Units/dose) were allowed during the modes to avoid interruption by clotting. Findings The mean activated partial thromboplastin (APTT) time as well as the doses of anticoagulation administered was highest with SHD and least with HAC and Evodial®. Mode H versus SHD had the highest rate of prematurely interrupted dialyses (33%, p = 0.008). The urea reduction rate was less with Evodial® vs. SHD (p < 0.01). One hypersensitivity reaction occurred with Evodial®. Changes in blood cell concentrations and triglycerides differed between the modes. Discussion If intermittent haemodialysis is necessary in patients at risk of bleeding, anticoagulation using HAC and Evodial® appeared most preferable with least administration of heparin, lowest APTT increase and lowest risk for prematurely clotted dialyzers in contrast to the least plausible H mode. Keywords Haemodialysis . Haemorrhage . Priming . Anticoagulation Background Standard intermittent haemodialysis (SHD) includes anticoagulation with unfractionated heparin (heparin) or low Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00228-017-2389-x) contains supplementary material, which is available to authorized users. * Malin S. E. Skagerlind 1 Department of Public Health and Clinical Medicine, University of Umea, Umea, Sweden 2 Department of Nephrology, Centre of Medicine, University Hospital of Umea, 90185 Umea, Sweden molecular weight heparin (LMWH) to avoid clotting of the extracorporeal circuit of the dialysis system [1]. In patients at risk of bleeding, while needing haemodialysis, one option is to use intravenous regional citrate infusion. This technique is so far only commercially available for continuous veno-venous haemodialysis (CVVHD) used in intensive care units and needs narrow clinical and laboratory surveillance. Except for a few centres with developed methods of narrow surveillance [4, 6, 10, 11], regional citrate anticoagulation (RCA) therefore is considered unsuitable for intermittent haemodialysis due to the need of extensive surveillance, to avoid risk of hypo- or hypercalcaemia. In untrained hands, RCA has been recommended to be limited to intensive care [8]. Therefore, other options may be considered for intermittent haemodialysis in patients at risk of bleeding. Eur J Clin Pharmacol Another way to restrict anticoagulation during intermittent haemodialysisis is by using saline flushes, heparin-coated dialyzers [2–9], dialysis fluid containing citrate[12, 13]or by combining heparin-coated dialyzers with citrate dialysate [14]. However, these methods may end up in frequent clotting (50% interrupted treatments) [15]. A pharmacological heparin coating of the dialyzer and the extracorporeal circuit, without using any heparin at the start, is another option. Such method is the manual priming by perfusion of the extracorporeal circuit with a combination of heparin and albumin that is discarded before intermittent haemodialysis [16, 17]. A prior in vitro study indicated that priming the extracorporeal circuit with only either saline or an albumin solution caused a greater risk for clotting in comparison to priming with heparin in saline or heparin and albumin in saline [18]. Saline flushes can cause fluid retention while regional citrate anticoagulation needs careful surveillance especially of ionized Ca2+ [12, 19]. A clotting of the extracorporeal circuit causes interrupted haemodialysis but also a blood loss up to 300 ml. Still, there is no golden standard for anticoagulation during intermittent haemodialysis in participants at bleeding risk [8]. The aim of this study was to clarify to what extent four different low-dose anticoagulant modes, versus standard haemodialysis, could reduce the administration of heparin while enabling dialysis. Materials and methods Participants on chronic intermittent haemodialysis (n = 23, 16 male) in a stable condition were included. The participants were consecutively informed and written consent to participate was obtained. Excluded were participants with a weight gain of more than 3 L between dialyses, access problems, acute infections or dementia. The reasons for end-stage kidney disease and intermittent haemodialysis were diabetic nephropathy (n = 6), glomerulonephritis (n = 5), nephrosclerosis (n = 5), polycystic kidney disease (n = 4) and interstitial nephritis (n = 3). Nine of the participants had diabetes mellitus. Included in daily medications were antiplatelets (acetylsalicylic acid: n = 14, clopidogrel: n = 1) and anticoagulants (warfarin: n = 6, subcutaneous dalteparin: n = 1). At different stages during the study period, five participants dropped out due to change of treatment regime (n = 1), impaired health (n = 1) and no given reason (n = 2). One participant terminated the study after having suffered from a side effect with Evodial®. Vascular accesses were arterial venous fistula (AV fistula, n = 12), central dialysis catheter (n = 10) and femoral dialysis catheter (n = 1). The catheter lock solutions used were heparin 5000 Units/ml (n = 5), and TauroLock™-HEP500 [(cyclo)taurolidine, citrate 4% and heparin (mucosa 5000 IU/ml)] (Tauro-Implant GmbH, Winsen, Germany) (n = 5). Dialysis devices were Gambro Artis™ with tubing system Artiset™ (Gambro Dasco S.p.A. Modella, Italy), Fresenius 5008 with tubing system Life Line Beta AV-Set ONLINEplus BVM 5008-R (Fresenius Medical Care AG & Co. Bad Homburg, Germany) and Fresenius 4008 with tubing (...truncated)