Oswald E.


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Efficacy of argatroban in critically ill patients with heparin resistance: a retrospective analysis.

Wed, 20/07/2016 - 4:08am

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Efficacy of argatroban in critically ill patients with heparin resistance: a retrospective analysis.

Semin Thromb Hemost. 2015 Feb;41(1):61-7

Authors: Treichl B, Bachler M, Lorenz I, Friesenecker B, Oswald E, Schlimp CJ, Pedross F, Fries D

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.

PMID: 25594496 [PubMed - indexed for MEDLINE]

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Results of rotational thromboelastometry, coagulation activation markers and thrombin generation assays in orthopedic patients during thromboprophylaxis with rivaroxaban and enoxaparin: a prospective cohort study.

Wed, 20/07/2016 - 4:08am

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Results of rotational thromboelastometry, coagulation activation markers and thrombin generation assays in orthopedic patients during thromboprophylaxis with rivaroxaban and enoxaparin: a prospective cohort study.

Blood Coagul Fibrinolysis. 2015 Mar;26(2):136-44

Authors: Oswald E, Velik-Salchner C, Innerhofer P, Tauber H, Auckenthaler T, Ulmer H, Streif W

Abstract
BACKGROUND: A prospective observational study was conducted in two clinical cohorts of patients to compare the effect of enoxaparin and rivaroxaban on rotational thromboelastometry (ROTEM), coagulation activation markers and thrombin generation.
METHODS: A total of 188 consecutive patients scheduled for major orthopedic surgery receiving 40-mg enoxaparin subcutaneously or 10-mg rivaroxaban orally were evaluated. Blood samples were taken before induction of anesthesia and on day 4 after surgery [postoperative day 4 (pod 4)]. The extrinsically (EXTEM) and the intrinsically (INTEM) activated ROTEM assay, antithrombin, prothrombin fragments (F1 + 2), thrombin-antithrombin complex (TAT) and D-dimers were measured, and the thrombodynamic ratio (TDR) was calculated. Thrombin generation was determined using calibrated automated thrombography. To compare the groups, changes (Δ) in baseline versus pod 4 were calculated.
RESULTS: EXTEM clotting time (CT) increased more with rivaroxaban than with enoxaparin; values above the reference range were observed (median ΔEXTEM-CT 15 vs. 5 s, P ≤ 0.0001). The increase in INTEM-CT (values remained within the normal ranges) was slight with enoxaparin and significant with rivaroxaban; ΔINTEM-CT was comparable. EXTEM-TDR, unchanged with rivaroxaban, increased significantly with enoxaparin, whereas ΔINTEM-TDR was comparable. ΔAT, ΔF1 + 2 and ΔTAT were significantly lower in the rivaroxaban group. Endogenous thrombin potential (ETP), unchanged with rivaroxaban, decreased significantly with enoxaparin; the maximal rising slope (mean velocity rate index) decreased more with rivaroxaban.
CONCLUSION: Data show that prolonged CT in the extrinsic ROTEM and thrombin generation assays reflecting initiation and propagation of thrombin may be useful for detecting treatment with rivaroxaban. The significance of observed differences in markers of coagulation needs to be investigated further.

PMID: 25396759 [PubMed - indexed for MEDLINE]

Categories: Publications list