Hemodilution and Endothelial Cell Regulation of Whole Blood Coagulation

Beyond localized damage to the circulatory system and surrounding tissue, trauma stresses endothelial cells throughout the vasculature, potentially leading to hemorrhagic or thrombotic complications away from the injury site.

Use a whole blood endothelial cell model to define the effects of crystalloid fluid therapy on protein C pathway regulation of tissue factor-initiated coagulation.

Tissue factor-initiated coagulation was studied in the presence of EA.hy926 cells. Blood was diluted to 70% or 40% using normal saline or lactated ringers. Analyses of coagulation dynamics included clot times, thrombin formation (thrombin-antithrombin complex), FV activation/inactivation, fibrinogen consumption, FXIII activation, and platelet activation.

In all donors, the onset of thrombin generation was not altered in 70% blood using either diluent; with the blood component reduced to 40%, clot time was prolonged two-fold when normal saline was utilized but was unchanged with lactated ringers. The timing of the activations of FV, fibrinogen, and platelets paralleled the effects of dilution on clot times. Extensive inactivation of FVa was observed in undiluted blood and where lactated ringers was the diluent but not in trials with 40% blood/60% normal saline.

Feedback inhibition of tissue factor-initiated coagulation by the protein C pathway is not compromised by hemodilution with crystalloids.