Hemostatic effect of activated recombinant factor VII (rFVIIa) in liver disease: studies in an in vitro model.
OBJECTIVE
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.
Tonda
Raúl
R
Servicio de Hemoterapia-Hemostasia, Hospital Clínic, Facultad de Medicina, IDIBAPS, Calle Villarroel 170, Barcelona 08036, Spain. agalan@clinic.ub.es
Galán
Ana María
AM
Pino
Marcos
M
Cirera
Isabel
I
Bosch
Jaume
J
Hernández
María Rosa
MR
Ordinas
Antonio
A
Escolar
Ginés
G
D000368:Aged; D000925:Anticoagulants / Q000494:pharmacology; D015942:Factor VIIa / Q000494:pharmacology*; D006487:Hemostasis / Q000187:drug effects*; D006495:Heparin, Low-Molecular-Weight / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008103:Liver Cirrhosis / Q000097:blood* / Q000503:physiopathology; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood; D015539:Platelet Activation / Q000187:drug effects; D010976:Platelet Count; D011498:Protein Precursors / Q000097:blood; D011516:Prothrombin; D011517:Prothrombin Time; D011994:Recombinant Proteins / Q000494:pharmacology
D000925:Anticoagulants; D006495:Heparin, Low-Molecular-Weight; D010446:Peptide Fragments; D011498:Protein Precursors; D011994:Recombinant Proteins; C029733:prothrombin fragment 1; C044183:prothrombin fragment 2; D011516:Prothrombin; D015942:Factor VIIa