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Prothrombin complex concentrate and recombinant prothrombin alone or in combination with recombinant factor X and FVIIa in dilutional coagulopathy: a porcine model
Author(s) -
MITTERLECHNER T.,
INNERHOFER P.,
STREIF W.,
LÖDL M.,
DANNINGER T.,
KLIMA G.,
HANSSON K.,
FRIES D.
Publication year - 2011
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/j.1538-7836.2011.04211.x
Subject(s) - fibrinogen , coagulopathy , medicine , prothrombin complex concentrate , coagulation , hydroxyethyl starch , prothrombin time , clotting time , recombinant dna , clotting factor , saline , anesthesia , pharmacology , chemistry , biochemistry , warfarin , gene , atrial fibrillation
Summary. 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 Methods: In 50 anesthetized pigs, ∼ 60% of the blood volume was withdrawn and replaced with hydroxyethyl starch.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. Conclusion: 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.