Fresh frozen plasma should be given earlier to patients requiring massive transfusion

J Trauma 2007;62:112-9.

Gonzales E, Moore F, Holcomb J, Miller C, Kozar R, Todd S, Cocanour C, Balldin B, McKinley B.




Purpose            The deadly triad of acidosis, hypothermia and coagulopathy for those who have suffered massive trauma with exsanguinating hemorrhage was identified more than 20 years prior. This specific identification led to fundamental changes in the initial emergency management of the severely injured patient. Despite all the advances in the science of trauma care, uncontrolled bleeding remains a leading cause of early death in trauma victims. The latest evidence has demonstrated that coagulopathies or a coagulopathic state begins much earlier than suspected, and is evident upon the patient’s arrival to the emergency room; most times before any resuscitative efforts have begun. The traditional massive transfusion practices are appearing to grossly underestimate the patient’s needs. The purpose of this study was to determine if a specific hospital’s massive transfusion protocol adequately corrected coagulopathies of the severely injured, and to assess whether uncorrected coagulopathy is predictive of increased mortality.

Background            Regional trauma systems triage the critically injured patients to Level 1 trauma centers where prevention of hypothermia, damage control surgery, massive transfusion protocol adherence and early intensive care unit triage for optimization of resuscitation efforts, takes precedence. These processes, while extremely advanced, are still unable to abort the fact that hemorrhage remains a leading cause of early death in civilian trauma and military combat casualty care. The researchers in this study had developed a formal massive transfusion protocol in the late 1990s. One component of their protocol was to transfuse fresh frozen plasma (FFP) after a trauma victim had received 6 units of packed red blood cells (PRBC). This delay in administering FFP until after the six units of packed red blood cells were administer was related to previous beliefs that posttraumatic coagulopathy develops over time due to the acidotic state, hypothermia, and resuscitation-related hemodilution and consumption of clotting factors. The most recent evidence is leading the experts to challenge this traditional thought process. Evidence is now pointing to a realization that patients are coagulopathic upon entrance to the emergency rooms well before aggressive resuscitation interventions take place. Newer information has identified that early prolongation of prothrombin time is the sentinel event; early administration of FFP is paramount in preventing coagulopathy; and the optimal replacement ratio of FFP:PRBC is 2:3. The recommendation now is that patients be given 2 units of FFP with the first unit of PRBCs (in those who are at high risk of requiring massive transfusion).

Methodology            This research was carried out as a prospective non experimental project. High risk patients who were admitted to the Shock Trauma ICU at Memorial Hermann Hospital in southeast Texas who met specific criteria underwent a 24 hour standardized shock resuscitation process directed by computerized decision support. Detailed data describing the patients’ clinical course and resuscitation process were obtained prospectively. Inclusion criteria were 1) major torso trauma, defined as injury of two or more abdominal organs, two or more long bone fractures, complex pelvic fracture, flail chest, or major vascular injury; 2) metabolic stress, defined as base deficit of ≥ 6 mEq/L within 12 hours of hospital admission; and 3) anticipated transfusion requirement of ≥ 6 units PRBCs within 12 hours of hospital admission, or age ≥ 65 years with any two of the three previous criteria. Brain injury patients were excluded due to a risk of worsening cerebral edema. Comprehensive hemodynamic data was gathered, including pulmonary artery pressure values at protocol and patient appropriate times. Additionally data was gathered on vasopressor and inotropic medication support, frequent hemoglobin and other pertinent laboratory values, arterial blood gas analysis, data describing hypothermia and coagulopathy, and any other clinical course of events (for example surgery or other procedures). At the beginning of the shock resuscitation protocol, baseline body core temperature, arterial blood gas data, and a coagulation profile comprising PT, international normalized ratio (INR), platelet count, partial thromboplastin time, and fibrinogen concentration were obtained. The same data was recorded on a scheduled basis for the duration of the 24 hour process. Additional data that characterized the pre-ICU course were recorded retrospectively. Data was recorded in to a Trauma Research Database. During the 51 months ending January 2003, there were 200 shock resuscitation protocol patients, of which 97 patients received a massive blood transfusion (>10 units of PRBCs). Data were then extracted from the Trauma Research Database for this study describing all patient demographics, the pre-ICU course, the ICU resuscitation, and outcomes with the focus on hypothermia, acidosis, and coagulopathy.

Result            Of the 97 patients who were resuscitated using this trauma center’s protocol and received massive transfusion (who made up this cohort), the following was found: 68 patients lived and 29 died. The mean age was 39 years; 61 were men. All patients (n = 79) required emergency surgery and/or interventional radiology procedures and were admitted to the ICU approximately 6.8 hours after emergency department admission. The mean severity of injury score was 29 for all. Blunt trauma was the predominate mechanism of injury. The mean INR upon arrival to the emergency room was 1.8. The patients were not hypothermic upon admission to the ICU and their base deficit, while still existing, had been approaching near normal values within 8 hours. This speaks to appropriate and aggressive warming mechanisms as well as management of any metabolic derangements. The protocol however, did not advocate sodium bicarbonate therapy in the emergency department, in the operating room, nor in the ICU unless arterial pH< 7.20. Statistical analysis found that the severity of the coagulopathy (indicated by the INR) measured at arrival in the ICU to be associated with survival outcome. Also found, with severe coagulopathy (INR ≥ 2.0), the probability of death was ≥ 50%.

Conclusion            The data indicated that acidosis and hypothermia were reasonably well managed at this Level 1 Trauma Center, and that their rigorous resuscitation protocols in terms if acidosis and hypothermia prevention, appeared stable. Coagulopathy did, however, remain a significant problem. These critically injured patients presented to the emergency department with an INR of ~1.8, indicating support of evidence that derangements in clotting cascades, and coagulopathy itself, were present upon arrival to the emergency room. Even though these patients were treated aggressively according to current protocols consistent with accepted trauma standard of care, coagulopathies were not ultimately definitively corrected. A moderate elevation in INR (1.4) persisted for these patients in the ICU for the last sixteen hours of this first 24 hour period. Within the ICU, transfusion of FFP was the primary intervention for coagulopathy correction, and a 1:1 ratio of FFP:PRBC used was. Do note that this ratio exceeds published recommendations. The authors of this research believe that failure to correct coagulopathy during the ICU resuscitation was largely attributable to inadequate pre-ICU interventions. The results of this study led the authors to develop and implement a standard protocol for prevention and correction of coagulopathy that starts in the emergency department. Their major policy change:  emphasis on early FFP administration in a ratio of 1 unit of FFP to 1 unit PRBC, beginning with the first unit of PRBC transfusion.



The evidence itself was more than troubling to these researchers. Uncorrected coagulopathy at ICU admission was found to be associated with ongoing transfusion requirements and the severity of the coagulopathy was found to be directly related to an increased risk of death. Finding evidence that the coagulopathy was present upon emergency room admission was paramount. The researchers found themselves scientifically assessing and questioning the entire process of their protocol. They reviewed the literature and most current studies as well as other’s protocols, and the prospective data gathering and trauma database providing them with a starting point in which to change a piece of the process. This is a great example of evidence based care!  Of course, it will be crucial to study whether the change in FFP to RBC ratio of administration upon initiation of the resuscitation protocol leads to improved patient outcomes.

As anesthetists, we frequently receive trauma victims directly from the emergency department. A major goal is to prevent the deadly trio of events: acidosis, coagulopathies, and hypothermia. Preventing coagulopathies is very difficult. For example, it is well known that 25% of those who are diagnosed with critical pelvic fractures, an unfortunate yet common trauma happenstance, experience major hemorrhage. We also know that persistent hypotension following trauma is usually the result of bleeding and massive hemorrhage. We infuse crystalloid and we begin the administration of blood products. This in and of itself has been known to worsen things. The crystalloid can lead to dilutional factor deficiencies, as can the red blood cells. We are used to diagnosing coagulopathies during an emergent anesthetic and typically this diagnosis is made after observed bleeding is noticed in the surgical field, usually long before we get stat laboratory results. Optimization of coagulation status during surgery and anesthesia correlates with favorable outcomes post- operatively. The evidence has now identified that trauma victims are presenting to emergency departments with critical laboratory values such as INRs of >1.8; this leads to a major change in trauma care critical pathways. Optimization of coagulation status and prevention of worsening hemorrhage is recommended immediately. It appears that it is no longer acceptable to begin massive transfusion of 4 or 5 units of PRBCs, large amounts of crystalloid, and then after the PRBC transfusion, call for the FFP. The analogy is similar to the patient who has begun the hypothermic spiral downward. We try and catch up to a normothermic state while some interventions are worsening the hypothermia. It then becomes extremely difficult to progress to normal physiologic states after a downward spiral has begun. The key appears to be identifying the situation early and warding off with treatment BEFORE it is too late to catch up.

Knowing that patient’s coagulopathic states have begun when entering the system has major implications on trauma anesthesia practice. The administration of FFP beginning at the same time as the initiation of massive transfusion protocol truly may lead to improvement of all resuscitation and interventional opportunities.


Mary A. Golinski, PhD, CRNA