Active-site inactivated FVIIa decreases thrombosis and necrosis in a random skin flap model of acute ischemia

J Surg Res. 2004 Dec;122(2):263-73. doi: 10.1016/j.jss.2004.06.014.


Background: Previous studies have emphasized the role of ischemia in inducing vascular thrombosis.

Materials and methods: Using a skin flap model of acute ischemia in the rat, we studied the effect of active-site inactivated factor VIIa (FVIIai), an inhibitor of tissue factor (TF), on tissue survival during acute ischemia.

Results: Ribonuclease protection analysis revealed an increase in TF in ischemic parts of the flap, and in situ hybridization localized this increase mainly to perivascular cells. A decrease in vascular thrombosis, as determined by fibrin immunostaining, was observed in FVIIai-treated animals. Intravenous administration of FVIIai had a positive impact on survival of the flap. Laser Doppler flowmetry revealed an increase in blood flow in the FVIIai-treated group. In treated animals, prothrombin time (PT) was increased (P < 0.01), whereas partial thromboplastin time (APTT) was unaltered; no significant impairment in systemic hemostasis (peri- and postoperative bleeding) was observed.

Conclusions: These findings demonstrate that TF expression is increased in perivascular cells in ischemic skin flaps and that FVIIai, by inhibiting TF, increases flap survival.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Animals
  • Blood Coagulation / drug effects
  • Factor VIIa / pharmacology
  • Female
  • Ischemia / complications
  • Ischemia / metabolism
  • Ischemia / pathology*
  • Ischemia / physiopathology
  • Necrosis
  • Rats
  • Rats, Wistar
  • Regional Blood Flow
  • Skin / blood supply*
  • Skin / metabolism
  • Skin / pathology
  • Surgical Flaps / pathology*
  • Thromboplastin / antagonists & inhibitors*
  • Thromboplastin / metabolism
  • Thrombosis / etiology
  • Thrombosis / pathology*
  • Time Factors
  • Tissue Survival / drug effects


  • Thromboplastin
  • Factor VIIa