title: Recombinant hirudin (HBW 023): biological data of ten patients with severe venous thrombo-embolism.
abstract: This study reports on the biological data of ten patients with acute venous thrombo-embolism. They were treated for 5 days with continuous intravenous infusion of a fixed dose (0.05 mg/kg/hr) of a recombinant hirudin (r-H HBW 023 Behringwerke, Germany). The plasma level of r-H (HBW 023), assessed by an anti-factor IIa amidolytic activity, was stable after Day 2 and showed considerable individual variations. It correlated with APTT ratio, suggesting that this test is a reliable tool to monitor therapy. In contrast, thrombin time was constantly over 120 sec (control 15 sec) and consequently was not a useful parameter. Prothrombin time showed a slight, but significant, prolongation, which was correlated with the increase of APTT ratio. There was no bleeding time prolongation, platelet count, or ATIII level decrease. Levels of thrombin-antithrombin III complexes, and D-dimers, which were high in all patients on admission, decreased during the course of the treatment but remained abnormal on Day 5, showing an ongoing hemostasis and fibrinolysis activation: this is consistent with the delayed, but only slightly decreased thrombin generation evidenced by thrombin generation test performed on Day 3. These results suggest that thrombin inhibition by rH-hirudin at this dosage is only partial, which allows the generation of traces of thrombin needed for the feed-back thrombin production generated by factor V and VIII activation.
authors.affiliation: Department of Hematology, Hôpital A. Béclère, Paris, France.
authors.forename: F
authors.initials: F
authors.lastname: Bridey
authors.forename: M
authors.initials: M
authors.lastname: Dreyfus
authors.forename: F
authors.initials: F
authors.lastname: Parent
authors.forename: A
authors.initials: A
authors.lastname: Bros
authors.forename: A M
authors.initials: AM
authors.lastname: Fischer
authors.forename: A
authors.initials: A
authors.lastname: Camez
authors.forename: G
authors.initials: G
authors.lastname: Simonneau
authors.forename: P
authors.initials: P
authors.lastname: Duroux
authors.forename: D
authors.initials: D
authors.lastname: Meyer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000990:Antithrombin III / Q000032:analysis; D015415:Biomarkers / Q000097:blood; D005260:Female; D006487:Hemostasis; D024764:Hirudin Therapy; D006629:Hirudins / Q000493:pharmacokinetics / Q000633:toxicity*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D010314:Partial Thromboplastin Time; D010447:Peptide Hydrolases / Q000032:analysis; D011517:Prothrombin Time; D011994:Recombinant Proteins / Q000493:pharmacokinetics / Q000627:therapeutic use / Q000633:toxicity; D012016:Reference Values; D013917:Thrombin / Q000378:metabolism; D013918:Thrombin Time; D013923:Thromboembolism / Q000097:blood / Q000188:drug therapy*; D013997:Time Factors
chemical_list: D015415:Biomarkers; D006629:Hirudins; D011994:Recombinant Proteins; C046193:antithrombin III-protease complex; D000990:Antithrombin III; D010447:Peptide Hydrolases; D013917:Thrombin