Clinical review: Fresh frozen plasma in massive bleedings - more questions than answers

Abstract

Fresh frozen plasma (FFP) is indicated for the management of massive bleedings. Recent audits suggest physician knowledge of FFP is inadequate and half of the FFP transfused in critical care is inappropriate. Trauma is among the largest consumers of FFP. Current trauma resuscitation guidelines recommend FFP to correct coagulopathy only after diagnosed by laboratory tests, often when overt dilutional coagulopathy already exists. The evidence supporting these guidelines is limited and bleeding remains a major cause of trauma-related death. Recent studies demonstrated that coagulopathy occurs early in trauma. A novel early formula-driven haemostatic resuscitation proposes addressing coagulopathy early in massive bleedings with FFP at a near 1:1 ratio with red blood cells. Recent retrospective reports suggest such strategy significantly reduces mortality, and its use is gradually expanding to nontraumatic bleedings in critical care. The supporting studies, however, have bias limiting the interpretation of the results. Furthermore, logistical considerations including need for immediately available universal donor AB plasma, short life after thawing, potential waste and transfusion-associated complications have challenged its implementation. The present review focuses on FFP transfusion in massive bleeding and critically appraises the evidence on formula-driven resuscitation, providing resources to allow clinicians to develop informed opinion, given the current deficient and conflicting evidence.

Figure 1

Recently proposed mechanism for coagulopathy in trauma. Tissue trauma activates the coagulation process via tissue factor (TF) and activated factor VII (FVIIa), formerly named the extrinsic pathway, to stop bleeding. Concomitantly, endothelial damage/ischaemia leads to release of physiologic anticoagulants and antifibrinolytics (that is, thrombomodulin (TM), protein C and tissue plasminogen activator (tPA)) due to inflammation and tissue hypoperfusion, to prevent thrombosis. Early coagulopathy develops when there is an imbalance in this process, with excessive anticoagulation, hyperfibrinolysis and consumption of clotting factors. Resuscitation with crystalloid and red blood cells (RBC) can cause/worsen dilution, acidosis and hypothermia. PAI-1, plasminogen activator inhibitor 1.