title: Efficacy and safety of anticoagulation with heparin versus heparin plus epoprostenol in patients undergoing extracorporeal liver support with Prometheus.
abstract: Anticoagulation for extracorporeal liver support is delicate due to underlying coagulation disorders in patients with liver failure and to the associated elevated bleeding risk. To date, there has been no detailed report on anticoagulation issues in patients treated with Prometheus, a device based on the principle of fractionated plasma separation and adsorption. We studied 17 patients from two centers treated with Prometheus, comparing standard anticoagulation with heparin (15 treatments) and a combination of heparin and the synthetic prostacyclin epoprostenol (22 treatments). Standard coagulation tests, proteins C and S, and thrombin-antithrombin (TAT) complex were determined, and adverse events were recorded. All but two treatments could be completed as scheduled, although filter exchange due to filter clotting was required in 24% of the treatments. Three out of 17 patients developed severe bleeding complications within 24 h of treatment. There were no overt thrombotic events. Addition of epoprostenol neither reduced coagulation-related adverse events nor improved standard coagulation parameters. Protein C, but not protein S, showed a significant reduction (23 +/- 18%) after Prometheus treatments, but levels rebounded to baseline within 18 h. TAT levels--a measure for activation of coagulation--were only altered by Prometheus in patients where TAT was already elevated before treatment. In conclusion, anticoagulation of Prometheus with heparin is feasible but still associated with a relatively high frequency of filter clotting and a considerable risk of severe bleeding in this high-risk patient population. As addition of epoprostenol did not prove beneficial, other strategies, such as regional anticoagulation with citrate, should be further evaluated.
authors: Department of Internal Medicine, Division of Nephrology and Hemodialysis, Medical University of Graz, Graz, Austria. peter.krisper@medunigraz.at
authors: Peter
authors: P
authors: Krisper
authors: Beate
authors: B
authors: Tiran
authors: Danilo
authors: D
authors: Fliser
authors: Bernd
authors: B
authors: Haditsch
authors: Vanessa
authors: V
authors: Stadlbauer
authors: Ronald
authors: R
authors: Otto
authors: Thomas
authors: T
authors: Ernst
authors: Ulrich
authors: U
authors: Kretschmer
authors: Rudolf E
authors: RE
authors: Stauber
authors: Hermann
authors: H
authors: Haller
authors: Herwig
authors: H
authors: Holzer
authors: Michael P
authors: MP
authors: Manns
authors: Kinan
authors: K
authors: Rifai
mesh_terms: D000925:Anticoagulants / Q000627:therapeutic use*; D000990:Antithrombin III; D001780:Blood Coagulation Tests; D004359:Drug Therapy, Combination; D011464:Epoprostenol / Q000627:therapeutic use*; D005260:Female; D006470:Hemorrhage / Q000209:etiology; D006493:Heparin / Q000627:therapeutic use*; D006801:Humans; D017093:Liver Failure / Q000097:blood / Q000628:therapy; D008297:Male; D008875:Middle Aged; D010447:Peptide Hydrolases / Q000097:blood; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D011486:Protein C / Q000378:metabolism; D017293:Protein S / Q000378:metabolism; D012189:Retrospective Studies; D016060:Sorption Detoxification / Q000009:adverse effects*; D013927:Thrombosis / Q000209:etiology / Q000517:prevention & control*
chemical_list: D000925:Anticoagulants; D010975:Platelet Aggregation Inhibitors; D011486:Protein C; D017293:Protein S; C046193:antithrombin III-protease complex; D000990:Antithrombin III; D006493:Heparin; D011464:Epoprostenol; D010447:Peptide Hydrolases