BACKGROUND/AIMS: There is clinical evidence for the efficacy of activated recombinant factor VII (rFVIIa) in patients with cirrhosis. The exact mechanism of action of rFVIIa in this clinical condition is unknown. We have explored effects of rFVIIa on hemostasis in cirrhotic patients using an in vitro perfusion technique. METHODS: Blood samples were drawn from control donors or from 11 patients previously diagnosed with cirrhosis (seven Child-Pugh B and four Child-Pugh C) and anticoagulated with low molecular weight heparin. rFVIIa was added to blood samples at therapeutic concentrations (0.5 or 1 microg/ml of plasma) and blood was recirculated through annular chambers containing damaged vascular segments. Presence of platelets and fibrin on the subendothelium were morphometrically quantified. RESULTS: Cirrhotic patients showed a diminished platelet interaction with the subendothelium compared to healthy donors (17.3% (9.28-28.88%) vs. 26.16% (19.96-54.5%), P<0.05). After addition of rFVIIa to cirrhotic samples, no differences in platelet covered surface were observed. However, fibrin formation was significantly improved after the addition of rFVIIa (from 51.81% (3.02-86.68%) to 86.94% (30.03-93.18%) and 89.05% (45.65-93.84%), respectively, P<0.05). CONCLUSIONS: Our data confirm a defective interaction of platelets with the subendothelium in cirrhotic patients. rFVIIa improved local fibrin formation at damaged sites and this mechanism could explain the beneficial action of rFVIIa in cirrhotic patients.
BACKGROUND/AIMS: There is clinical evidence for the efficacy of activated recombinant factor VII (rFVIIa) in patients with cirrhosis. The exact mechanism of action of rFVIIa in this clinical condition is unknown. We have explored effects of rFVIIa on hemostasis in cirrhotic patients using an in vitro perfusion technique. METHODS: Blood samples were drawn from control donors or from 11 patients previously diagnosed with cirrhosis (seven Child-Pugh B and four Child-Pugh C) and anticoagulated with low molecular weight heparin. rFVIIa was added to blood samples at therapeutic concentrations (0.5 or 1 microg/ml of plasma) and blood was recirculated through annular chambers containing damaged vascular segments. Presence of platelets and fibrin on the subendothelium were morphometrically quantified. RESULTS: Cirrhotic patients showed a diminished platelet interaction with the subendothelium compared to healthy donors (17.3% (9.28-28.88%) vs. 26.16% (19.96-54.5%), P<0.05). After addition of rFVIIa to cirrhotic samples, no differences in platelet covered surface were observed. However, fibrin formation was significantly improved after the addition of rFVIIa (from 51.81% (3.02-86.68%) to 86.94% (30.03-93.18%) and 89.05% (45.65-93.84%), respectively, P<0.05). CONCLUSIONS: Our data confirm a defective interaction of platelets with the subendothelium in cirrhotic patients. rFVIIa improved local fibrin formation at damaged sites and this mechanism could explain the beneficial action of rFVIIa in cirrhotic patients.
Authors: Irene Lopez-Vilchez; Ulla Hedner; Carmen Altisent; Maribel Diaz-Ricart; Gines Escolar; Ana M Galan Journal: Am J Pathol Date: 2011-06 Impact factor: 4.307
Authors: Henning Grønbaek; Søren P Johnsen; Peter Jepsen; Mette Gislum; Hendrik Vilstrup; Ulrik Tage-Jensen; Henrik T Sørensen Journal: BMC Gastroenterol Date: 2008-05-24 Impact factor: 3.067
Authors: Gines Escolar; Victor Fernandez-Gallego; Eduardo Arellano-Rodrigo; Jaume Roquer; Joan Carles Reverter; Victoria Veronica Sanz; Patricia Molina; Irene Lopez-Vilchez; Maribel Diaz-Ricart; Ana Maria Galan Journal: PLoS One Date: 2013-11-11 Impact factor: 3.240