Efficacy of fibrinogen and prothrombin complex concentrate used to reverse dilutional coagulopathy--a porcine model.
BACKGROUND
This study was conducted to assess whether the combined administration of fibrinogen and prothrombin complex concentrate (PCC) enables the reversal of dilutional coagulopathy resulting from intended blood loss and fluid replacement, and whether this treatment reduces further blood loss and mortality.


METHODS
In 20 anaesthetized pigs, approximately 65% of the estimated blood volume was withdrawn and replaced with the same amount of hydroxyethyl starch (6% HES 130/0.4) to mimic blood loss and to develop a dilutional coagulopathy. Pigs (randomized) received either fibrinogen (200 mg kg(-1)) and PCC (35 IU kg(-1)) (n=10), or placebo (n=10). Thereafter, a standard liver laceration was performed to induce uncontrolled haemorrhage. The subsequent blood loss and survival time were determined as primary outcome variables. Throughout the experiment serial blood samples were obtained to assess the competence of the haemostatic system using standard coagulation tests, modified Thrombelastograph measurements (ROTEM) and electron microscopy clot imaging.


RESULTS
As compared with baseline, after haemodilution both groups showed statistically significant impairment of haemostasis as measured with standard coagulation tests and thrombelastography. These parameters significantly improved after administration of the study drugs while aPPT measurements remained unchanged. Blood loss after liver injury was significantly less in the treatment group as compared with placebo: 240 ml (50-830) vs 1800 ml (1500-2500) (P<0.0001). All treated animals survived, whereas 80% of the placebo group died (P<0.0001).


CONCLUSIONS
During haemodilution, substitution of fibrinogen and PCC causes an enhancement of coagulation and final clot strength. This reversal of dilutional coagulopathy may reduce blood loss and mortality when large amounts of colloids are needed to maintain normovolaemia during huge blood losses.
Fries
D
D
Division of General and Surgical Intensive Care Medicine, Innsbruck Medical University Anichstrasse 35, 6020 Innsbruck, Austria. dietmar.fries@uibk.ac.at
Haas
T
T
Klingler
A
A
Streif
W
W
Klima
G
G
Martini
J
J
Wagner-Berger
H
H
Innerhofer
P
P
D000818:Animals; D001777:Blood Coagulation; D001778:Blood Coagulation Disorders / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D001779:Blood Coagulation Factors / Q000627:therapeutic use*; D016063:Blood Loss, Surgical; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D005340:Fibrinogen / Q000627:therapeutic use*; D005440:Fluid Therapy / Q000009:adverse effects*; D006439:Hemodynamics; D006490:Hemostatics / Q000627:therapeutic use*; D006895:Hydroxyethyl Starch Derivatives / Q000009:adverse effects; D008855:Microscopy, Electron, Scanning; D013552:Swine; D013916:Thrombelastography
D001779:Blood Coagulation Factors; D006490:Hemostatics; D006895:Hydroxyethyl Starch Derivatives; C025667:prothrombin complex concentrates; D005340:Fibrinogen