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      Selection of Anticoagulants for Leukocytapheresis Therapy in Cases of Active Ulcerative Colitis

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          Abstract

          Background and Aim: Leukocytapheresis (LCAP) is an extracorporeal leukocyte removal therapy that removes immunocompetent leukocytes from the peripheral blood. Nafamostat mesilate (NM) is the most commonly used anticoagulant for LCAP due to various benefits associated with its use, such as a reduced likelihood of bleeding and minimization of adverse reactions caused by contact between blood and the LCAP device. However, adverse reactions have also been reported with NM administration. We reviewed the safety of anticoagulants other than NM, from the perspective of bradykinin production and the consequent drop in blood pressure during treatment. Methods: For each of 10 patients with ulcerative colitis, we used four types of anticoagulants sequentially [NM (30–50 mg), heparin, low-molecular-weight heparin (LMWH) and NM (1 mg), and LMWH] for LCAP. We then examined the changes in the blood bradykinin concentrations from the perspective of adverse reactions during LCAP. Results: The bradykinin production levels from Cellsorba EX varied, depending on the type of anticoagulant used. NM alone (30–50 mg) or LMWH + NM (1 mg) inhibited bradykinin production, whereas heparin alone or LMWH alone significantly accelerated it. However, an excessive fall of blood pressure was not noted in any of the cases. Use of LMWH alone was frequently associated with pressure elevations in the column. Conclusions: Given the significant benefits of minimized adverse reactions of LCAP and of continuation of LCAP, we suggest that an appropriate selection of the anticoagulant(s) may allow safer execution of LCAP.

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          Most cited references 21

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          Adsorptive Granulocyte and Monocyte Apheresis versus Prednisolone in Patients with Corticosteroid-Dependent Moderately Severe Ulcerative Colitis

          Background/Aim: Active ulcerative colitis (UC) is often associated with increased peripheral granulocytes and monocytes/macrophages which show activation behavior and prolonged survival time. Further, mucosal granulocyte level parallels intestinal inflammation and can predict UC relapse. Accordingly, our aim was to see if adsorptive granulocyte/monocyte apheresis (GMA) can promote remission and spare steroid in patients with steroid-dependent (SD) UC. Methods: 69 SD patients, at the time of relapse, were randomly assigned to groups I (n = 46) and II (n = 23). The mean dose of prednisolone (PSL) was 12 mg/day/patient, CAI (clinical activity index) 9.2 in both groups. Group I patients were given up to 11 GMA sessions over 10 weeks with Adacolumn; in group II, the mean dose of PSL was increased to 30 mg/day/patient. Results: At week 12, 83% of group I and 65% of group II patients were in remission, CAI in group I was 1.7 (p < 0.001) and in group II, 2.5 (p < 0.001). Further, during the 12 weeks of treatment, the cumulative amount of PSL received per patient was 1,157 mg in group I and 1,938 mg in group II (p = 0.001). Conclusions: GMA appeared to be an effective adjunct to standard drug therapy of moderately severe UC by promoting remission and sparing steroids.
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            New synthetic inhibitors of C1r̄, C1 esterase, thrombin, plasmin, kallikrein and trypsin

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              Leukocytapheresis in ulcerative colitis: results of a multicenter double-blind prospective case-control study with sham apheresis as placebo treatment.

              Leukocytapheresis (LCAP) is a method of therapeutic apheresis that removes peripheral leukocytes. Previous studies showed that in patients with ulcerative colitis (UC), LCAP was more effective than high-dose steroid therapy, and it had few adverse effects. We investigated LCAP in a multicenter study using active and sham devices in a double-blind study in order to elucidate the placebo effect of extracorporeal treatment including anticoagulant medication. Twenty-five patients with active UC of severe or moderately severe grade were enrolled and assigned to the active group or the sham group. Six patients were excluded from the study and 19 (10 in the active group and nine in the sham group) were evaluated. LCAP (treatment using an active device or a sham device) was performed once a week for 5 wk, followed by two additional sessions during the next 4 wk at 2-wk intervals. Steroids and other medications were continued at the same dosage for 4 wk, which included a 2-wk pre-observation period and the first 2 wk after the start of the LCAP treatment. New medications or increase in the dosage of previous medication were prohibited until evaluation was conducted. The clinical activity index (CAI) value of UC, indicated that the active group showed a significantly greater improvement (80%, 8/10) than the sham group (33%, 3/9; p<0.05). Adverse effects were observed in five patients (one in the active group and four in the sham group). None of these effects was severe and none of the sessions was terminated as a consequence of the adverse effects. The results confirmed that LCAP is a safe and effective therapeutic option for patients with active UC.
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                Author and article information

                Journal
                BPU
                Blood Purif
                10.1159/issn.0253-5068
                Blood Purification
                S. Karger AG
                0253-5068
                1421-9735
                2007
                September 2007
                30 August 2007
                : 25
                : 4
                : 370-376
                Affiliations
                Department of Gastroenterology, DOKKYO Medical University, Mibu, Japan
                Article
                107712 Blood Purif 2007;25:370–376
                10.1159/000107712
                17785966
                © 2007 S. Karger AG, Basel

                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.

                Page count
                Figures: 5, References: 26, Pages: 7
                Categories
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