The effect of fibrinogen substitution on reversal of dilutional coagulopathy:: An in vitro model

Colloids and crystalloids are usually administered as treatment for hypovolemia in severely injured patients. However, dilution of clotting factors and platelets together with impaired fibrinogen polymerization are associated with fluid therapy and may aggravate hemorrhage, thus worsening final outcome of these patients. We investigated, in an in vitro model, whether the addition of fibrinogen to diluted blood samples can reverse dilutional coagulopathy. Blood from 5 healthy male volunteers was diluted by 60%, using lactated Ringer's solution, 4% modified gelatin solution, or 6% hydroxyethyl starch 130/0.4, as well as the combination of lactated Ringer's solution with either of the 2 colloid solutions. Thereafter, aliquots of diluted blood samples were incubated with 3 different concentrations of fibrinogen (0.75, 1.5, and 3.0 mg/mL). Measurements were performed by modified thrombelastography (ROTEM (R); Pentapharm, Munich, Germany). After 60% dilution, clotting times increased, whereas clot firmness and fibrin polymerization decreased significantly. After administration of fibrinogen, clotting times decreased and clot firmness, as well as fibrin polymerization, increased in all diluted blood samples. The effect of in vitro fibrinogen substitution on ROTEM (R) variables was dependent on the fibrinogen dosage and the type of solution used to dilute the blood samples.