Dear Sir,

We thank Dr. Vassallo et al. for their interesting observations to our study in which we demonstrated that the outcome of a group of septic shock patients treated with the Coupled Plasma-Filtration and Adsorption (CPFA) was influenced by the volume of plasma processed (Vp), and not by the timing of initiation [1]. Dr. Vassallo et al. argue that the use of regional citrate anticoagulation (RCA) instead of intravenous heparin would increase the running time of the CPFA, and consequently the Vp, which is considered a proxy of the intensity of the treatment. Indeed, Dr. Vassallo’s remark makes sense, considering that previous studies demonstrated (a) a dose-effect relationship between the Vp and the outcome, which is better when this variable exceeds 0.20 L/kg/session [2, 3], and (b) the superiority of RCA over intravenous heparin in patients undergoing renal replacement therapy in terms of duration of the extracorporeal circuit, systemic bleeding and transfusion requirements [4]. Moreover, in septic patients undergoing extracorporeal treatments, finding the right dose of heparin can be challenging due to a number of conditions such as the presence of possible sources of hemorrhage, the low levels of Antithrombin III and the hypercoagulable state determined by the interaction between inflammatory mediators and coagulation factors [5]. For these reasons and a few citrate contraindications, RCA has been recommended even in the absence of an increased risk of bleeding [6]. Our group is well aware of these considerations, but RCA was not yet available in our -Department at the time of the study. However, despite the well-known heparin-related shortcomings, we think that its mere replacement with RCA could hardly influence the outcome in septic patients who did not present with increased risk of bleeding. Actually, factors other than clotting can reduce the overall Vp, including the hemodynamic instability, and perhaps more importantly, the interruption of the CPFA due to the need for surgical or diagnostic procedures that cannot be performed at the bedside. In addition, the recent COMPACT II study, which has been prematurely suspended due to an excess mortality rate in the treatment group, required the use of RCA instead of heparin during the CPFA [7, 8].

All authors have no conflict of interest to disclose.

This research did not receive any funding from agencies in the public, commercial, or not-for-profit sectors.

1.
Berlot G, Falini S, Negro V, et al: Influence of timing of initiation and volume of processed plasma on the outcome of septic shock patients treated with coupled plasma filtration and adsorption (CPFA). Blood Purif 2018; 46: 274–278.
2.
Livigni S, Bertolini G, Rossi C, Ferrari F, Giardino M, Pozzato M, et al: Efficacy of coupled plasma filtration adsorption (CPFA) in patients with septic shock: a multicenter randomised controlled clinical trial. BMJ Open 2014; 4:e003536.
3.
Berlot G, Agbedjro A, Tomasini A, Bianco F, Gerini U, Viviani M, et al: Effects of the volume of processed plasma on the outcome, arterial pressure and blood procalcitonin levels in patients with severe sepsis and septic shock treated with coupled plasma filtration and adsorption. Blood Purif 2014; 37: 146–151.
4.
Morabito S, Pistolesi V, Tritapepe L, Fiaccadori E: Regional citrate anticoagulation for RRTs in critically ill patients with AKI. Clin J Am Soc Nephr 2014; 9: 2173–2188.
5.
Levi M, van der Poll T: Coagulation and sepsis. Thromb Res 2017; 149: 38–44.
6.
Kidney Disease: improving global outcomes (KDIGO): acute kidney injury work group: KDIGO clinical practice guidelines for acute kidney injury. Kidney Int 2012;(suppl 2): 1–138.
7.
Gruppo Italiano per la Valutazione degli Interventi in Terapia Intensiva. COMPACT: COMbining Plasmafiltration and Adsorption Clinical Trial. http://www.giviti.marionegri.it/Compact.asp (accessed May 20, 2018).
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.