Protective Effects of Fresh Frozen Plasma on Vascular Endothelial Permeability, Coagulation, and Resuscitation After Hemorrhagic Shock Are Time Dependent and Diminish Between Days 0 and 5 After Thaw

Abstract

Background Clinical studies have shown that resuscitation with fresh frozen plasma (FFP) is associated with improved outcome after severe hemorrhagic shock (HS). We hypothesized that in addition to its effects on hemostasis, FFP has protective and stabilizing effects on the endothelium that translate into diminished endothelial cell (EC) permeability and improved resuscitation in vivo after HS. We further hypothesized that the beneficial effects of FFP would diminish over 5 days of routine storage at 4°C. Methods EC permeability was induced by hypoxia and assessed by the passage of 70-kDa Dextran between monolayers. Thrombin generation time and coagulation factor levels or activity were assessed in FFP. An in vivo rat model of HS and resuscitation was used to determine the effects of FFP on hemodynamic stability. Results Thawed FFP inhibits EC permeability in vitro by 10.2-fold. Protective effects diminish (to 2.5-fold) by day 5. Thrombin generation time is increased in plasma that has been stored between days 0 and 5. In vivo data show that day 0 FFP is superior to day 5 FFP in maintaining mean arterial pressure in rats undergoing HS with resuscitation. Conclusion Both in vitro and in vivo studies show that FFP has beneficial effects on endothelial permeability, vascular stability, and resuscitation in rats after HS. The benefits are independent of hemostasis and diminish between days 0 and 5 of storage.

Comparing Normothermic Machine Perfusion Preservation With Different Perfusates on Porcine Livers From Donors After Circulatory Death

“…Furthermore, the Steen plus RBC perfusate consists of a plasma-like solution supplemented with RBCs that lacks several factors present in physiological plasma. Pati et al recently suggested that physiological plasma has beneficial effects on endothelial permeability and vascular stability after hemorrhagic shock (41). More studies are needed to investigate further the role of leukocytes, platelets and plasma factors in ex vivo organ preservation.…”

Optimal trauma resuscitation with plasma as the primary resuscitative fluid: the surgeon's perspective

“…At the same time, the beneficial effect of plasma on endothelial permeability has been outlined. 17 When endothelial cell (EC) permeability is induced by hypoxia, thrombin, or VEGF, plasma has been shown to repair endothelial tight junctions and decrease paracellular permeability. However crystalloid has no effect in these in vitro models.…”

Volume Management and Resuscitation in Trauma

“…It contains all the clotting factors, fibrinogen, proteins C and S, and albumin. It is available in 250 and 500 cc bags that must be thawed and used within 24 h or it becomes classified as frozen plasma, which has been shown to contain significantly less clotting factors and a diminished ability to restore intravascular volume [60]. FFP has also been shown to be significantly less immunogenic than pRBCs [61,62], and decreases vascular leakage through stabilization of the endothelial membrane [60].…”