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      Fibrinogen Reduction and Bleeding Complications in Plasma Exchange, Immunoadsorption and a Combination of the Two

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          Abstract

          Background: Immunoadsorption (IAS) and therapeutic plasma exchange (TPE) are considered safe although fibrinogen is removed. To date no comparison of fibrinogen reduction and associated risk of bleeding in apheresis exists. Methods: Retrospective analysis of TPE, three IAS adsorbers, and combined TPE/IAS regarding fibrinogen reduction and bleeding incidence in 67 patients (1,032 treatments). Results: TPE and TPE/IAS reduced fibrinogen by 64 ± 11% and 58 ± 9%, leading to concentrations <100 mg/dl in 20 and 17% of treatments, respectively. IAS decreased fibrinogen less than TPE (26 ± 6%, p < 0.0001), resulting in fibrinogen concentrations <100 mg/dl in 1% of treatments. The processed volume correlated with reduction in TPE (r = 0.64, p < 0.01), but not in IAS. Bleeding occurred in 1.3% (IAS), 2.3% (TPE) and 3.1% (TPE/IAS) of treatments. Conclusion: Hypofibrinogenemia occurs in 20% of patients after TPE and TPE/IAS, but rarely after IAS. IAS removes fibrinogen independently of volume processed. Overall, bleeding is rare in apheresis.

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          Most cited references 22

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          Guidelines for the use of fresh-frozen plasma, cryoprecipitate and cryosupernatant.

          The indications for transfusing fresh-frozen plasma (FFP), cryoprecipitate and cryosupernatant plasma are very limited. When transfused they can have unpredictable adverse effects. The risks of transmitting infection are similar to those of other blood components unless a pathogen-reduced plasma (PRP) is used. Of particular concern are allergic reactions and anaphylaxis, transfusion-related acute lung injury, and haemolysis from transfused antibodies to blood group antigens, especially A and B. FFP is not indicated in disseminated intravascular coagulation without bleeding, is only recommended as a plasma exchange medium for thrombotic thrombocytopenic purpura (for which cryosupernatant is a possible alternative), should never be used to reverse warfarin anticoagulation in the absence of severe bleeding, and has only a very limited place in prophylaxis prior to liver biopsy. When used for surgical or traumatic bleeding, FFP and cryoprecipitate doses should be guided by coagulation studies, which may include near-patient testing. FFP is not indicated to reverse vitamin K deficiency for neonates or patients in intensive care units. PRP may be used as an alternative to FFP. In the UK, PRP from countries with a low bovine spongiform encephalopathy incidence is recommended by the Departments of Health for children born after 1 January 1996. Arrangements for limited supplies of single donor PRP of non-UK origin are expected to be completed in 2004. Batched pooled commercially prepared PRP from donors in the USA (Octaplas) is licensed and available in the UK. FFP must be thawed using a technique that avoids risk of bacterial contamination. Plastic packs containing any of these plasma products are brittle in the frozen state and must be handled with care.
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            Transfusion-related acute lung injury: epidemiology and a prospective analysis of etiologic factors.

            Transfusion-related acute lung injury (TRALI) is a life-threatening complication of hemotherapy. We report a series of 90 TRALI reactions in 81 patients secondary to transfusion with whole blood platelets (72 reactions), apheresis platelets (2), packed red cells (15), and plasma (1). The overall prevalence was 1 in 1120 cellular components. To examine the epidemiology of TRALI, we completed a nested case-control study of the first 46 patients with TRALI compared with 225 controls who had received transfusions. We then completed a prospective analysis of possible biologic response modifiers responsible for 51 of the TRALI cases, including human leukocyte antigen (HLA) class I, class II, and granulocyte antibodies in donors and neutrophil (PMN) priming activity in the plasma of the implicated units and recipients. Two groups were at risk: patients with hematologic malignancies (P <.0004) and patients with cardiac disease (P <.0006). TRALI was associated with older platelets (P =.014). In the prospective study, antileukocyte antibodies were found in only 3.6% of cases. The implicated blood components had greater PMN priming activity than controls (P <.05), and compared with pretransfusion samples, TRALI patients' plasma demonstrated increases in both interleukin 6 (IL-6) and lipid (neutral lipids and lysophosphatidylcholines) priming activity (P <.05). We conclude that TRALI may be more frequent than previously recognized and that patient susceptibility, product age, and increased levels of bioactive lipids in components may predispose patients to TRALI. TRALI, like the acute respiratory distress syndrome, may be a 2-event phenomenon with both recipient predisposition and factors in the stored units playing major roles.
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              Clinical effectiveness of fresh frozen plasma compared with fibrinogen concentrate: a systematic review

              Introduction Haemostatic therapy in surgical and/or massive trauma patients typically involves transfusion of fresh frozen plasma (FFP). Purified human fibrinogen concentrate may offer an alternative to FFP in some instances. In this systematic review, we investigated the current evidence for the use of FFP and fibrinogen concentrate in the perioperative or massive trauma setting. Methods Studies reporting the outcome (blood loss, transfusion requirement, length of stay, survival and plasma fibrinogen level) of FFP or fibrinogen concentrate administration to patients in a perioperative or massive trauma setting were identified in electronic databases (1995 to 2010). Studies were included regardless of type, patient age, sample size or duration of patient follow-up. Studies of patients with congenital clotting factor deficiencies or other haematological disorders were excluded. Studies were assessed for eligibility, and data were extracted and tabulated. Results Ninety-one eligible studies (70 FFP and 21 fibrinogen concentrate) reported outcomes of interest. Few were high-quality prospective studies. Evidence for the efficacy of FFP was inconsistent across all assessed outcomes. Overall, FFP showed a positive effect for 28% of outcomes and a negative effect for 22% of outcomes. There was limited evidence that FFP reduced mortality: 50% of outcomes associated FFP with reduced mortality (typically trauma and/or massive bleeding), and 20% were associated with increased mortality (typically surgical and/or nonmassive bleeding). Five studies reported the outcome of fibrinogen concentrate versus a comparator. The evidence was consistently positive (70% of all outcomes), with no negative effects reported (0% of all outcomes). Fibrinogen concentrate was compared directly with FFP in three high-quality studies and was found to be superior for > 50% of outcomes in terms of reducing blood loss, allogeneic transfusion requirements, length of intensive care unit and hospital stay and increasing plasma fibrinogen levels. We found no fibrinogen concentrate comparator studies in patients with haemorrhage due to massive trauma, although efficacy across all assessed outcomes was reported in a number of noncomparator trauma studies. Conclusions The weight of evidence does not appear to support the clinical effectiveness of FFP for surgical and/or massive trauma patients and suggests it can be detrimental. Perioperatively, fibrinogen concentrate was generally associated with improved outcome measures, although more high-quality, prospective studies are required before any definitive conclusions can be drawn.
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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
                2014
                December 2014
                04 December 2014
                : 38
                : 2
                : 160-166
                Affiliations
                aInternal Medicine III/Clinical Division of Nephrology and Dialysis, bCenter for Medical Statistics, Informatics, and Intelligent Systems, and cClinical Institute of Pathology, Medical University of Vienna, Vienna, Austria
                Author notes
                *Peter Biesenbach, MD, Division of Nephrology and Dialysis, Medical University of Vienna, Währinger Gürtel 18-20, AT-1090 Vienna (Austria), E-Mail Peter.biesenbach@meduniwien.ac.at
                Article
                367682 Blood Purif 2014;38:160-166
                10.1159/000367682
                25501972
                © 2014 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: 3, Tables: 3, Pages: 7
                Categories
                Original Paper

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