Novel Resuscitation Strategies in Severe Trauma: Comment

We read with great interest the review of “Early Fibrinogen Replacement to Treat the Endotheliopathy of Trauma: Novel Resuscitation Strategies in Severe Trauma” by Douin et al. This article explores endothelial dysfunction that can occur with the coagulopathy of trauma, its association with worse morbidity and mortality from end-organ dysfunction, and the role of plasma-based substrates for restoring endothelial integrity. Furthermore, it highlights the specific role fibrinogen may play to stabilize the endothelial glycocalyx, beyond its role in reversing acquired coagulopathy. Of note, the review states that the fibrinogen concentration in cryoprecipitate is 125 mg/dl, and we submit that a more accurate approximation of fibrinogen concentration in cryoprecipitate is 10-fold higher, in the range of 1,250 mg/dl.

There is a high degree of variability of fibrinogen concentration in cryoprecipitate and other human-derived blood components. A unit of cryoprecipitate contains the high molecular weight proteins that precipitate as frozen plasma is slowly thawed, including fibrinogen, von Willebrand factor, factor VIII, factor XIII, fibronectin, and smaller amounts of other proteins. With each unit of cryoprecipitate derived from the plasma of a single unit of blood, actual fibrinogen content per unit varies considerably, and the Association for the Advancement of Blood and Biotherapies and the U.S. Food and Drug Administration only mandate that each cryoprecipitate unit contain greater than 150 mg of fibrinogen.  Furthermore, units can be pooled in packs of 4, 5, 8 or 10, depending on institutional blood bank policy. Several review articles have consolidated available information about the comparative fibrinogen concentration in fresh frozen plasma, cryoprecipitate, and fibrinogen concentrate (table 1).

Recent society guidelines have increased their target plasma fibrinogen level in patients to 150 to 200 mg/dl in the setting of trauma, obstetric, and severe hemorrhage.  The mathematical concept of an asymptote highlights that products have a diminishing return as they approach their native concentration and is modeled by Collins et al.  This concept, along with the effect of hemodilution of the low-concentration, high-volume solution of fresh frozen plasma, underscores the importance of anesthesiologists recognizing the relative concentration of fibrinogen among blood products used for fibrinogen replacement and the ineffectiveness of fresh frozen plasma for successful repletion of acquired hypofibrinogenemia.