ADAMTS13 exerts a thrombolytic effect in microcirculation

Thromb Haemost. 2012 Sep;108(3):527-32. doi: 10.1160/TH12-01-0046. Epub 2012 Jul 10.


Recombinant tissue plasminogen activator (r-tPA) is the drug of choice for thrombolysis, but it is associated with a significant risk of bleeding and is not always successful. By cleaving von Willebrand factor (VWF), the metalloprotease ADAMTS13 (a disintegrin-like and metalloprotease with thrombospondin type I repeats-13) down-regulates thrombus formation in injured vessels. We investigated whether recombinant ADAMTS13 (r-ADAMTS13) induces thrombolysis in vivo in mice. Thrombosis was produced by ferric chloride-induced (FeCl(3)) injury in the venules of a dorsal skinfold chamber. Phosphate-buffered saline (PBS, vehicle), r-tPA or r-ADAMTS13, supplemented with hirudin (to stop on-going thrombin generation), was directly applied onto the occluded vessel, and thrombus dissolution was evaluated by intravital microscopy. The incidence of blood flow restoration significantly increased 30 minutes (min) after r-ADAMTS13 vs. PBS treatment (60% vs. 0%, p<0.05) and 60 min after r-tPA treatment (75% vs. 17%, p<0.05). Both r-tPA and r-ADAMTS13 significantly reduced thrombus size 60 min after their superfusion (53.2% and 62.3% of the initial thrombus size, p<0.05 and p<0.01, respectively). Bleeding occurred in all r-tPA-treated chambers, while it was absent in mice treated with r-ADAMTS13 or PBS. We observed that, similar to r-tPA, r-ADAMTS13 can dissolve occlusive thrombi induced by FeCl(3) injury in venules. In contrast to r-tPA, the in vivo thrombolytic effect of ADAMTS13 was not associated with any signs of haemorrhage. ADAMTS13 could represent a new therapeutic option for thrombolysis.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • ADAM Proteins / pharmacology
  • ADAM Proteins / therapeutic use*
  • ADAM Proteins / toxicity
  • ADAMTS13 Protein
  • Animals
  • Chlorides / toxicity
  • Computer Systems
  • Disease Models, Animal
  • Drug Evaluation, Preclinical
  • Ferric Compounds / toxicity
  • Fibrinolytic Agents / pharmacology
  • Fibrinolytic Agents / therapeutic use*
  • Fibrinolytic Agents / toxicity
  • Hemorrhage / chemically induced
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microcirculation / drug effects
  • Microscopy / methods
  • Recombinant Proteins / pharmacology
  • Recombinant Proteins / therapeutic use
  • Recombinant Proteins / toxicity
  • Skin Window Technique
  • Thrombolytic Therapy* / adverse effects
  • Tissue Plasminogen Activator / pharmacology
  • Tissue Plasminogen Activator / therapeutic use
  • Venous Thrombosis / chemically induced
  • Venous Thrombosis / drug therapy*
  • Venules


  • Chlorides
  • Ferric Compounds
  • Fibrinolytic Agents
  • Recombinant Proteins
  • Tissue Plasminogen Activator
  • ADAM Proteins
  • ADAMTS13 Protein
  • ADAMTS13 protein, human
  • ferric chloride