NDT Advance Access originally published online on September 2, 2006
Nephrology Dialysis Transplantation 2006 21(12):3601; doi:10.1093/ndt/gfl518
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Reply
Email: dario.frank{at}ukaachen.deSir,
Thank you for the opportunity to comment on the letter by Chanard et al. [1]. They raise a number of points dealing with technical details of our coated surface.
The method described by Chanard et al. is distinct from ours, since they rinse the circuit with heparin 5000 U/l which is adsorbed onto the surface, so that 
1600 U stick to the membrane. Rinsing with saline removes 15% of the heparin. In vitro data for rinsing with plasma, which is more potent for removing heparin from a surface than saline, have not been published. Not surprisingly, during clinical dialysis, relevant heparin levels (>0.2 antiXa U/ml) were found in the circulation after 15 and 60 min of treatment with AN69ST in sessions without systemic heparin administration [3], which is in contrast to our covalent coating.
The Genius system was used since it is a simple, cheap dialysis machine with comparably little blood-air contact. The dialysis tubing system was unchanged. A conventional bubble trap is not part of the system (it contains a ‘flow chamber’) and does not represent a study-specific ‘provocative innovation’.
The goal of our article was to introduce the technology of stable covalent heparin coating, which is ‘ready-to-use’, in the care of chronic haemodialysis patients and to show its feasibility for an anticoagulant-free dialysis. The method is primarily suitable for patients with bleeding risk, especially when regional citrate anticoagulation or saline flush are too cumbersome or not available. The study was performed in patients with normal coagulatory potential. A control dialysis without coating and without systemic anticoagulation, which would have been a way to show superiority of the coating, was felt to be unethical, and therefore was not part of the study plan.
The coating method used in our publication has been evaluated in more than 60 000 cardiopulmonary bypass procedures in cardiac surgery since 1996. AOThel is a trademark and the coating is CE-certified. Several independent investigators have confirmed the improvement of biocompatibility and the reduced thrombogenicity of the coated surfaces [4], (unpublished data by Wendel HP, University of Tubingen, Germany, and Mottaghy K, Department of Physiology, RWTH University, Aachen). The coating avoids potentially harmful tensides like polyethyleneimine and tries to copy the endothelial proteoglycane coating by binding the heparin to a surface-fixed protein. More specific technical details are an essential part of the patent and therefore confidential.
Of course, the presence of the coating on the material surfaces was checked, and all materials used in the circuit, including the F60 high-flux dialyser, were coated. The achieved heparin surface concentration was 0.1–0.3 µg/cm2. The stability of the coating was also checked for each lot. The performance of the dialysers as far as the small molecule elimination and the water permeability are concerned was not significantly affected by the coating process (unpublished data).
It is implausible to assume that the observed decrease of the thrombogenicity of the dialysis circuits was due to the heparin coating of the tubing only, given that the dialyser represents >95% of the circuit surface. Furthermore, a recent paper by Lucchi et al. in 2006 [5] showed that the tubing alone did not significantly activate coagulation during haemodialysis.
Our article was intended as a proof-of-concept study to show that an anticoagulant-free dialysis is feasible in stable chronic dialysis patients. Our data show that the coagulation activation is not abolished by the coating but comparable with that achieved under a standard systemic anticoagulation, allowing 4.5 h of regular dialysis without any use of heparin and without complications in five patients with normal coagulation system and platelet count. Our promising pilot results will require verification in a larger study.
Conflict of interest statement. None declared.
Department of Nephrology
University Hospital RWTH Aachen
D-52057 Aachen, Germany
References
- Chanard J, Lavaud S, Paris B, et al. (2005) Assessment of heparin binding to the AN69 ST hemodialysis membrane: I. preclinical studies. ASAIO Journal 51:342–347.[CrossRef][Web of Science][Medline]
- Lavaud S, Canivet E, Wuillai A, et al. (2003) Optimal anticoagulation strategy in haemodialysis with heparin-coated polyacrylonitrile membrane. Nephrol Dial Transplant 18:2097–2104.
[Abstract/Free Full Text] - Lavaud S, Paris B, Maheut H, et al. (2005) Assessment of heparin binding AN69 ST hemodialysis membrane: clinical studies without heparin administration. ASAIO Journal 51:348–351.[CrossRef][Web of Science][Medline]
- Baksaas ST, Videm V, Fosse E, et al. (1999) In vitro evaluation of new surface coatings for extracorporeal circulation. Perfusion 14:11–19.
[Abstract/Free Full Text] - Lucchi L, Ligabue G, Marietta M, et al. (2006) Activation of coagulation during hemodialysis: effect of blood lines alone and whole extracorporeal circuit. Artif Organs 30:106–110.[CrossRef][Web of Science][Medline]
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