Recombinant hirudin (HBW 023): biological data of ten patients with severe venous thrombo-embolism

Am J Hematol. 1995 May;49(1):67-72. doi: 10.1002/ajh.2830490111.

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.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antithrombin III / analysis
  • Biomarkers / blood
  • Female
  • Hemostasis
  • Hirudin Therapy*
  • Hirudins / pharmacokinetics
  • Hirudins / toxicity*
  • Humans
  • Infusions, Intravenous
  • Male
  • Middle Aged
  • Partial Thromboplastin Time
  • Peptide Hydrolases / analysis
  • Prothrombin Time
  • Recombinant Proteins / pharmacokinetics
  • Recombinant Proteins / therapeutic use
  • Recombinant Proteins / toxicity
  • Reference Values
  • Thrombin / metabolism
  • Thrombin Time
  • Thromboembolism / blood
  • Thromboembolism / drug therapy*
  • Time Factors

Substances

  • Biomarkers
  • Hirudins
  • Recombinant Proteins
  • antithrombin III-protease complex
  • Antithrombin III
  • Peptide Hydrolases
  • Thrombin