Physiology and Management of Massive Transfusion

Plasma/Fresh Frozen Plasma

Overall, developing massive transfusion protocols has been an important therapeutic tool for effectively managing life-threatening hemorrhage after trauma.¹⁵ Plasma/FFP contains multiple factors for hemostasis and has increasingly been considered a critical component. Most of the analyses reporting beneficial effects of high plasma ratios are retrospective and include plasma/FFP transfusion:RBC ratios of 1:1 or more from trauma. The optimal ratio of plasma/FFP:RBCs is not known, but prospective studies including a current investigation from the North American Pragmatic, Randomized Optimal Platelets and Plasma Ratios study (ClinicalTrials.gov number, NCT01545232) will provide new information. This randomized trial from 12 different medical centers will evaluate outcomes from trauma patients who will require massive transfusions as defined by the administration of more than 10 units of RBCs within 24 hours and will assess overall mortality. There are major differences in the management of severe hemorrhage between the United States and Europe. Based on currently published European guidelines, clinicians are now using factor concentrates based on thromboelastometry (ROTEM) guidance, with prothrombin complex concentrates, fibrinogen, and factor XIII. Fibrinogen and other factor concentrates have been used for many years in Europe, as cryoprecipitate is not available in all countries. However, therapy is multimodal and requires hemodynamic and hemostatic support as well as efforts to address the underlying bleeding source. An example of a massive transfusion protocol is shown in Figure 31-1.⁶

Platelet Administration

Following traumatic injury or significant postoperative bleeding, the critical platelet count for transfusion is often based on consensus therapy rather than true objective data. Although a count of 50,000 or more is recommended, the threshold for administration of platelets, especially in cases of dilutional coagulopathy, remains unclear as do the ideal ratio of platelets to other blood components. Most protocols attempt to develop a strategy that mimics whole blood replacement with RBC:plasma/FFP: platelets at a 1:1:1 ratio with massive bleeding.^13,14

However, assessing platelet function in the bleeding patient is not possible; therefore, empiric platelet administration is often undertaken. If patients have received antiplatelet agents recently, then even the existing platelets and platelet counts may not be helpful. Therefore, if patients have received antiplatelet agents or are bleeding after separation from cardiopulmonary bypass, then platelet dysfunction should be suspected and platelet concentrates considered. However, there are significant potential adverse events associated with platelet administration.⁶

Antifibrinolytic Agents

Because of the critical role of fibrinolysis with severe bleeding and trauma, the antifibrinolytic agent tranexamic acid is increasingly used as a therapeutic strategy. Inhibiting fibrinolysis during acute bleeding has many beneficial effects including preserving initial clot formation at a bleeding site that may otherwise be broken down, similar to the clot destruction seen in hemophilia.⁶ The Clinical Randomization of an Antifibrinolytic in Significant Hemorrhage (CRASH 2) study focused on tranexamic acid as a therapeutic agent in traumatic injury in a prospective randomized placebo-controlled trial of 1-g loading followed by 1 g over 8 hours in 20,211 trauma patients. Overall mortality was reduced from 14.5% to 16.0% (relative risk, 0.91; P = 0.0035), as were deaths due to bleeding (4.9% vs. 5.7%; relative risk, 0.85; P = 0.0077). Tranexamic acid is also approved in the United States for excessive menstrual bleeding at a dose of 1.3 g three times a day (~4 g total dose), without significant reported safety issues. Despite the efficacy and safety of tranexamic acid, clinicians often substitute epsilon-aminocaproic acid, another lysine analog, although this agent has not been studied as well as tranexamic acid and is not available in some European countries.

Procoagulants

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