A new recombinant thrombolytic and antithrombotic agent with higher fibrin affinity - a staphylokinase variant. An in-vivo study

Thromb Haemost. 2007 Jun;97(6):1037-45. doi: 10.1160/th06-10-0562.


The recombinant protein SAK-RGD-K2-Hir is characterized by its fibrin-specific properties of plasminogen activation combined with antithrombin and antiplatelet activities. It was previously shown in our in-vitro studies to be a more potent and faster-acting thrombolytic agent compared with standard r-SAK. In order to document the effects of the thrombolytic potential of SAK-RGD-K2-Hir we examined this protein in an electrically induced carotid artery thrombosis model and stasis-induced venous model in rats. In the arterial thrombosis model, a bolus injection of SAK-RGD-K2-Hir was less effective than rt-PA and r-SAK. However, the most effective in the improvement and maintenance of carotid patency and in arterial thrombus mass reduction was SAK-RGD-K2. In contrast, all r-SAK derivatives reduced venous thrombus weight significantly in comparison to r-SAK and r-Hir. However, the most observable decrease in thrombus weight was obtained after application of recombinant proteins containing the r-Hir. The bleeding time was significantly prolonged in the animals treated with proteins containing r-Hir at a dose of 1.0 mg/kg. There were no observable changes in plasma fibrinogen concentration. In conclusion, our findings show thrombolytic activity in intravenous bolus injection of the novel thrombolytic agent SAK-RGD-K2-Hir in rats. Although this protein compares favourably with r-SAK in rat venous thrombolysis, we were unable to confirm the beneficial effects of SAK-RGD-K2-Hir over r-SAK and rt-PA in the carotid artery thrombolysis model. Furthermore, our results also suggest that SAK-RGD-K2-Hir bears a risk of bleeding, but this may be true for higher doses.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bleeding Time
  • Blood Coagulation / drug effects*
  • Carotid Artery Thrombosis / blood
  • Carotid Artery Thrombosis / drug therapy*
  • Carotid Artery Thrombosis / metabolism
  • Carotid Artery Thrombosis / physiopathology
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Electric Stimulation
  • Fibrin / metabolism*
  • Fibrinolytic Agents / adverse effects
  • Fibrinolytic Agents / metabolism
  • Fibrinolytic Agents / pharmacology*
  • Hemorrhage / chemically induced
  • Hirudins / adverse effects
  • Hirudins / metabolism
  • Hirudins / pharmacology*
  • Ligation
  • Male
  • Metalloendopeptidases / adverse effects
  • Metalloendopeptidases / metabolism
  • Metalloendopeptidases / pharmacology*
  • Partial Thromboplastin Time
  • Rats
  • Rats, Wistar
  • Recombinant Fusion Proteins / adverse effects
  • Recombinant Fusion Proteins / metabolism
  • Recombinant Fusion Proteins / pharmacology*
  • Thrombin Time
  • Time Factors
  • Tissue Plasminogen Activator / pharmacology
  • Vascular Patency / drug effects*
  • Venae Cavae / surgery
  • Venous Thrombosis / blood
  • Venous Thrombosis / drug therapy*
  • Venous Thrombosis / metabolism


  • Fibrinolytic Agents
  • Hirudins
  • Recombinant Fusion Proteins
  • SAK-RGD-K2-Hir
  • Fibrin
  • Tissue Plasminogen Activator
  • Metalloendopeptidases