Prothrombin complex concentrate and recombinant prothrombin alone or in combination with recombinant factor X and FVIIa in dilutional coagulopathy: a porcine model.
BACKGROUND
This study was conducted to assess whether newly developed recombinant clotting factor concentrates enable the reversal of dilutional coagulopathy.


METHODS
In 50 anesthetized pigs, ~60% of the blood volume was withdrawn and replaced with hydroxyethyl starch. Pigs were randomized to receive either 200 mg kg(-1) fibrinogen (n = 10), fibrinogen and 35 IU kg(-1) prothrombin complex concentrate (PCC) (n = 10), fibrinogen and 4 mg kg(-1) recombinant human factor II (rhFII) concentrate (n = 10), fibrinogen and a three-factor combination (3F) of 4 mg kg(-1) rhFII, 0.006 mg kg(-1) recombinant human FVIIa and 0.32 mg kg(-1) recombinant human FX (n = 10), or saline (n = 10). Thereafter, a standardized liver laceration was performed to induce uncontrolled hemorrhage. Survival time and blood loss were determined, and standard coagulation tests and thrombelastometry were performed.


RESULTS
Fibrinogen combined with rhFII or PCC improved survival. Blood loss was significantly decreased in all groups as compared with the animals receiving saline. Clotting time was significantly shortened in the animals treated with fibrinogen and PCC, as well as in those treated with fibrinogen and 3F. One animal died after administration of fibrinogen and PCC.


CONCLUSIONS
Following hemodilution, a combination of fibrinogen and PCC, rhFII or 3F enhances coagulation and final clot strength. Mortality was reduced statistically significantly only in the animals treated with fibrinogen and rhFII or PCC, whereas administration of the combination of fibrinogen and PCC caused a fatal thromboembolic complication. The combination of fibrinogen and rhFII might be effective in reversing dilutional coagulopathy and may reduce blood loss in cases of dilutional coagulopathy.
Department of Anesthesiology and Critical Care Medicine, Innsbruck Medical University, Innsbruck, Austria.
T
T
Mitterlechner
P
P
Innerhofer
W
W
Streif
M
M
Lödl
T
T
Danninger
G
G
Klima
K
K
Hansson
D
D
Fries
D000818:Animals; D001778:Blood Coagulation Disorders / Q000188:drug therapy*; D005170:Factor X / Q000494:pharmacology* / Q000627:therapeutic use; D011516:Prothrombin / Q000494:pharmacology* / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D013552:Swine
D011994:Recombinant Proteins; D011516:Prothrombin; D005170:Factor X; C025337:Factor IIa