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• W2065651454 abstract "Introduction. Patients who have received platelet inhibitory drugs may constitute a challenge in management of perioperative bleeding [ [1] Kaluza G.L. Joseph J. Lee J.R. Raizner M.E. Raizner A.E. Catastrophic outcomes of noncardiac surgery soon after coronary stenting. J Am Coll Cardiol. Apr 2000; 35: 1288-1294 Abstract Full Text Full Text PDF PubMed Scopus (666) Google Scholar ]. Administration of DDAVP has been proposed to be effective in partially restoring platelet function following aspirin or gpIIb/IIIa antagonists [ 2 Reiter R.A. Mayr F. Blazicek H. Galehr E. Jilma-Stohlawetz P. Domanovits H. et al. Desmopressin antagonizes the in vitro platelet dysfunction induced by GPIIb/IIIa inhibitors and aspirin. Blood. Dec 15 2003; 102: 4594-4599 Crossref PubMed Scopus (127) Google Scholar , 3 Mannucci P.M. Vicente V. Vianello L. Cattaneo M. Alberca I. Coccato M.P. et al. Controlled trial of desmopressin in liver cirrhosis and other conditions associated with a prolonged bleeding time. Blood. Apr 1986; 67: 1148-1153 PubMed Google Scholar ], and reduces transfusion needs after surgery [ [4] Crescenzi G. Landoni G. Biondi-Zoccai G. Pappalardo F. Nuzzi M. Bignami E. et al. Desmopressin reduces transfusion needs after surgery: a meta-analysis of randomized clinical trials. Anesthesiology. Dec 2008; 109: 1063-1076 Crossref PubMed Scopus (107) Google Scholar ]. Thus, in many institutions, DDAVP is part of the established algorithm for management of perioperative bleeding [ [5] Weber C.F. Schneider A.C. Kirschning T. Hofstetter C. Zacharowski K. Gorlinger K. Therapeutic options for perioperatively acquired platelet dysfunctions. Anaesthesist. Sep 2009; 58 (938): 931-936 Crossref PubMed Scopus (13) Google Scholar ]. Furthermore, an increasing number of institutions use thromboelastometry for guidance of transfusion and administration of haemostatic drugs [ 6 Theusinger O.M. Spahn D.R. Ganter M.T. Transfusion in trauma: why and how should we change our current practice?. Curr Opin Anaesthesiol. Apr 2009; 22: 305-312 Crossref PubMed Scopus (95) Google Scholar , 7 Fries D. Innerhofer P. Schobersberger W. Time for changing coagulation management in trauma-related massive bleeding. Curr Opin Anaesthesiol. Apr 2009; 22: 267-274 Crossref PubMed Scopus (96) Google Scholar ]. The importance of correcting fibrinogen and fibrin polymerisation in management of perioperative bleeding has recently been emphasized by a series of experimental [ 8 Fenger-Eriksen C. Anker-Moller E. Heslop J. Ingerslev J. Sørensen B. Thrombelastographic whole blood clot formation after ex vivo addition of plasma substitutes: improvements of the induced coagulopathy with fibrinogen concentrate. Br J Anaesth. 2005; 94: 324-329 Crossref PubMed Scopus (136) Google Scholar , 9 Fries D. Krismer A. Klingler A. Streif W. Klima G. Wenzel V. et al. Effect of fibrinogen on reversal of dilutional coagulopathy: a porcine model. Br J Anaesth. May 27 2005; 95: 172-177 Crossref PubMed Scopus (164) Google Scholar ] and clinical studies [ 10 Rahe-Meyer N. Pichlmaier M. Haverich A. Solomon C. Winterhalter M. Piepenbrock S. et al. Bleeding management with fibrinogen concentrate targeting a high-normal plasma fibrinogen level: a pilot study. Br J Anaesth. Jun 2009; 102: 785-792 Crossref PubMed Scopus (223) Google Scholar , 11 Karlsson M. Ternstrom L. Hyllner M. Baghaei F. Flinck A. Skrtic S. et al. Prophylactic fibrinogen infusion reduces bleeding after coronary artery bypass surgery. A prospective randomised pilot study. Thromb Haemost. Jul 2009; 102: 137-144 PubMed Google Scholar , 12 Fenger-Eriksen C. Jensen T.M. Kristensen B.S. Jensen K.M. Tonnesen E. Ingerslev J. et al. Fibrinogen substitution improves whole blood clot firmness after dilution with hydroxyethyl starch in bleeding patients undergoing radical cystectomy: a randomized, placebo-controlled clinical trial. J Thromb Haemost. May 2009; 7: 795-802 Crossref PubMed Scopus (211) Google Scholar ]. It may be speculated, that DDAVP influences levels of fibrinogen and fibrin polymerisation due to renal water retention. Thus, the aim of the present study was to investigate the effect of DDAVP on levels of fibrinogen and fibrin polymerisation. We tested the null hypotheses that DDVAP do not change levels of fibrinogen nor fibrin polymerisation. Materials and methods. A total of 16 patients (11 Females, 5 males, mean age=36) referred to our Haemophlia Centre for investigation of primary haemostatic defects were enrolled in the study. All patients had received a test dose of DDAVP (Desmopressin, Octostim®, Ferring Pharmaceuticals Ltd, Berkshire, UK) 0.2 μg/kg subcutaneous or intranasal. Blood samples (2.8 % citrate) were taken immediately, as well as 6 hours after DDAVP. Levels of fibrinogen [g/L] were measured by a photometric Clauss method using a Sysmex CA-1500 (TOA, Kobe, Japan). Platelet poor plasma was (PPP) diluted with Owrens and activated with bovine thrombin (SysmexFbg, TOA, Kobe, Japan). Furthermore, fibrin polymerisation was evaluated by ROTEM® Thromboelastometry, (TEM Innovations, Munich, Germany). Platelet poor plasma was transferred to a pre-warmed plastic cup containingcytochalasin D, a strong platelet inhibitor (FibTEM®, TEM Innovations), followed by activation with tissue factor (ExTEM®, TEM Innovations). Fibrin polymerisation was evaluated by recording maximum clot firmness (MCF, [mm]). Based on pilot data a sample size of 16 pair would have a 90 % power to detect a difference between FibTEM means of 1.43 mm or more with a significance level (alpha) of 0.05 (two-tailed). Recorded data did not follow a Gaussian distribution as evaluated by Kolmogorov-Smirnov test, thus data were compared using a non-parametric Wilcoxon matched-pairs signed-ranks test. A two-tailed P value less than 0.05 was considered statistical significant. Results: Levels of fibrinogen changed significantly from median=2.30 g/L (range=1.69-3.95) before DDAVP to median=2.06 g/L (range=1.61-3.22) after DDAVP, p=0.0327. The median difference was 0.14 g/L (95%CI: -0.08 - 0.43), corresponding a relative change of 6 %. A total of 11 patients had a drop in their level of fibrinogen (changes ranged from −0.01 to −1.18 g/L), whereas 2 had an increase (0.08 and 1.12 g/L) and 3 showed no change. However, fibrin polymerisation as evaluated by the MCF value of the FibTEMPPP assay showed no significant change. The MCF of the FibTEMPPP before DDAVP was median=25 mm (range=14-28) as compared to a MCF of median=22 mm (range=16-30) after DDAVP, p=0.1763. The median difference was 1.0 mm (95%CI: -0.4 - 3.0), corresponding a relative change of 4 %. A total of 8 patients revealed a reduction in their MCF (changes ranged from −1 to −7 mm), whereas 4 patients had an increase (changes ranged from 1 to 3 mm) and 3 showed no change (measurements failed in 1 patient due to technical problems). Discussion. Data showed that fibrinogen decreases following administration of DDAVP. However, fibrin polymerisation revealed no statistical relevant changes. Historically, the threshold level of fibrinogen has been 1 g/L. However, the critical threshold levels of fibrinogen are currently being challenged, thus depending on the clinical scenario, the suggested new threshold levels may be much higher than 1 g/L [ 13 Charbit B. Mandelbrot L. Samain E. Baron G. Haddaoui B. Keita H. et al. The decrease of fibrinogen is an early predictor of the severity of postpartum hemorrhage. J Thromb Haemost. Feb 2007; 5: 266-273 Crossref PubMed Scopus (521) Google Scholar , 14 Karlsson M. Ternstrom L. Hyllner M. Baghaei F. Nilsson S. Jeppsson A. Plasma fibrinogen level, bleeding, and transfusion after on-pump coronary artery bypass grafting surgery: a prospective observational study. Transfusion. Oct 2008; 48: 2152-2158 Crossref PubMed Scopus (187) Google Scholar ]. Recently, thromboelastometry algorithms have been used to guide haemostatic intervention in the perioperative setting. In these guidelines, intervention with fibrinogen is suggested if the FibTEM is ≤5-7 mm [ 6 Theusinger O.M. Spahn D.R. Ganter M.T. Transfusion in trauma: why and how should we change our current practice?. Curr Opin Anaesthesiol. Apr 2009; 22: 305-312 Crossref PubMed Scopus (95) Google Scholar , 7 Fries D. Innerhofer P. Schobersberger W. Time for changing coagulation management in trauma-related massive bleeding. Curr Opin Anaesthesiol. Apr 2009; 22: 267-274 Crossref PubMed Scopus (96) Google Scholar ]. Based on our study it seems unlikely that treatment with DDAVP will have major clinical interference with levels of fibrinogen or fibrin polymerisation. The addition of Cytochalasin D to PPP avoided the bias DDAVP could have caused by increasing the MCF via improvement of platelet function. From a diagnostic point of view, the individual changes in levels of fibrinogen and MCF seems negligible in most cases. However, it should be noted that bleeding patients often develop a low level of fibrinogen and MCF, thus if DDAVP is administered to a patient close to the threshold levels of fibrinogen and/or MCF, this may be clinically important." @default.
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• W2065651454 title "Levels of fibrinogen and thromboelastometry fibrin polymerisation following treatment with desmopressin (DDAVP)" @default.
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