title: Efficacy of argatroban in critically ill patients with heparin resistance: a retrospective analysis.
abstract: The patients who do not respond even to very high dosages of heparin are assumed to suffer from heparin resistance. The aim of this study was to investigate whether critically ill patients suffering from heparin resistance generally have low antithrombin III (AT) levels, and if the direct thrombin inhibitor argatroban in that case can be an effective option to achieve prophylactic anticoagulation. The study was conducted at the Department for General and Surgical Intensive Care Medicine at the University Hospital Innsbruck. We retrospectively included all patients between 2008 and 2012, who received argatroban because of poor response to high-dosage heparin prophylaxis. The period under observation lasted in total for 9 days, 2 days of anticoagulation with unfractionated heparin (UFH) and 7 days with argatroban. The primary objective was to investigate if after 7 (± 1) hours of switching to argatroban the activated partial thromboplastin time (aPTT) levels were in a prophylactic range of 45 to 55 seconds. Further objectives were to assess the AT level, side effects such as bleeding or thromboembolism, platelet count, correlation between organ function and argatroban dose as well as any need for allogeneic blood products. The study population, consisting of 5 women and 15 men with a mean (± standard deviation, SD) age of 54.6 ± 16.3 years, differed in many clinical aspects. A median (interquartile range) heparin dose of 1,000, 819 to 1,125 IU/h was administered for 2 days and failed in providing a prophylactic anticoagulation measured by the aPTT. The mean aPTT level with heparin treatment was 38.5 seconds (± 4.7) its change within that period was not significant. After switching to argatroban, the mean increase of the aPTT levels in all study patients amounted from 38.5 to 48.3 seconds (p < 0.001). The rise in aPTT clearly reaches sufficient prophylactic anticoagulant levels. The maintenance of prophylactic aPTT levels was achieved over the period of 1 week. There was neither a correlation found between low-AT levels and occurrence of heparin resistance, nor between the simplified acute physiology score II and the administered argatroban dose (r = -0.224, p = 0.342). The results of the present study indicate that argatroban is an effective alternative therapy, especially in critically ill patients, to achieve prophylactic anticoagulation when heparin resistance occurs.
authors.affiliation: Department of Anesthesia and Intensive Care Medicine, Medical University Innsbruck, Austria.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Treichl
authors.affiliation: Department of General and Surgical Intensive Care Medicine, Medical University Innsbruck, Innsbruck, Austria.
authors.forename: Mirjam
authors.initials: M
authors.lastname: Bachler
authors.affiliation: Department of General and Surgical Intensive Care Medicine, Medical University Innsbruck, Innsbruck, Austria.
authors.forename: Ingo
authors.initials: I
authors.lastname: Lorenz
authors.affiliation: Department of General and Surgical Intensive Care Medicine, Medical University Innsbruck, Innsbruck, Austria.
authors.forename: Barbara
authors.initials: B
authors.lastname: Friesenecker
authors.affiliation: Department of Anesthesia and Intensive Care Medicine, Medical University Innsbruck, Austria.
authors.forename: Elgar
authors.initials: E
authors.lastname: Oswald
authors.affiliation: Ludwig Boltzmann Institute, For Experimental and Clinical Traumatology, AUVA Research Centre, Vienna, Austria.
authors.forename: Christoph J
authors.initials: CJ
authors.lastname: Schlimp
authors.affiliation: Department of Medical Statistics, Informatics and Health Economics, Medical University Innsbruck, Innsbruck, Austria.
authors.forename: Florian
authors.initials: F
authors.lastname: Pedross
authors.affiliation: Department of General and Surgical Intensive Care Medicine, Medical University Innsbruck, Innsbruck, Austria.
authors.forename: Dietmar
authors.initials: D
authors.lastname: Fries
mesh_terms: D000925:Anticoagulants / Q000627:therapeutic use; D000990:Antithrombin III / Q000378:metabolism; D001120:Arginine / Q000031:analogs & derivatives; D016638:Critical Illness; D004351:Drug Resistance; D005260:Female; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010875:Pipecolic Acids / Q000627:therapeutic use*; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D012189:Retrospective Studies; D013449:Sulfonamides
chemical_list: D000925:Anticoagulants; D010875:Pipecolic Acids; D010975:Platelet Aggregation Inhibitors; D013449:Sulfonamides; D000990:Antithrombin III; D006493:Heparin; D001120:Arginine; C031942:argatroban