Managing coagulopathy is a vexing challenge for trauma specialists caring for patients who have experienced major trauma and require massive transfusion. Research has shown that in severe bleeding, coagulation factors do not decrease equally, and the optimal level of fibrinogen in achieving hemostatic resuscitation is unknown. This prompted researchers to examine the association between fibrinogen levels and outcomes following massive transfusion, findings presented in this issue of Strategies.

In acute trauma patients with significant blood loss, finding the right balance between replacing red cell mass and correcting systemic coagulation defects is a substantial clinical challenge, as hemorrhage remains the leading cause of preventable death after injury. Considerable contemporary research has been focused in this area as the trauma field seeks to better understand acute trauma-related coagulopathies in an effort to improve patient outcomes. Studies have suggested that fibrinogen may be one of the more vulnerable coagulation factors, but its role in hemostatic resuscitation is incompletely understood. This led researchers at the University of Southern California in Los Angeles to examine the association between plasma fibrinogen levels and outcomes in acutely injured patients who received massive transfusion (J Am Coll Surg 2013;216:290–7).

“Our group is interested in coagulopathy and resuscitation associated with acute traumatic injury, which is an incredibly complex process. There are different aspects that contribute to coagulopathy, and fibrinogen depletion may be one of the most important. So we were interested in exploring what impact fibrinogen levels might have on survivability in acutely traumatized individuals,” said co-author Ira Shulman, MD, director of laboratories for the Los Angeles County+University of Southern California (LAC+USC) Healthcare Network.

Shulman and his colleagues performed a 12-year retrospective study of massively transfused trauma patients admitted to the LAC+USC Medical Center surgical intensive care unit (SICU). Defining a massive transfusion as 10 or more packed red blood cell (PRBC) units during the first 24 hours after admission, the researchers identified 758 patients, of which 260 had a documented fibrinogen test result upon admission to SICU. The latter group formed the basis of the study. The researchers defined normal fibrinogen level as ≥180 mg/dL, abnormal as ≥101 to <180 mg/dL, and critical as ≤100 mg/dL.

The authors found that as fibrinogen levels declined, all other coagulation markers worsened in a step-wise fashion. For example, mean international normalized ratio, activated partial thromboplastin time, and prothrombin time for patients with normal fibrinogen levels were 1.27, 37.4, and 15.2, respectively, versus 2.47, 114.3, and 27.2 in those with critical levels.

The researchers also found, after adjusting for differences between groups, that patients with critical fibrinogen levels had significantly higher mortality at 24 hours compared with those with either abnormal or normal levels. Overall, 31.5% of patients with critical fibrinogen levels died within 24 hours of admission, compared with 5.3% and 4.3% in those with abnormal and normal levels, respectively. In addition, patients with critical fibrinogen levels were more than twice as likely to die in the hospital as those with normal levels, 51.9% versus 18.5%, with an adjusted odds ratio of 2.6.

From these findings the authors concluded that fibrinogen ≤100 mg/dL is a strong independent risk factor for mortality. They also suggested this study raises issues that warrant further analysis, such as the interaction between fibrinogen levels and the process of hyperfibrinolysis, and what effect fibrinogen-rich resuscitation products might have. “These are preliminary observations,” cautioned Shulman. “They need to be reproduced in appropriately constructed controlled trials.”

A trauma care researcher not involved in the study agreed that the field is in need of higher quality research. “There’s been a resurgence in interest in the coagulation system and we’re just now beginning to unveil some uncertainty we never appreciated before. This is partly due to the availability of assays that allow real-time assessment in whole blood,” said Ernest E. Moore, MD. “While I say there’s enormous interest, there’s also a dearth of randomized trials to establish anything. So this study is like a lot in our field right now that simply raise questions without answering them.” Moore is vice-chair of surgery at the University of Colorado Health Sciences Center in Denver.

He went on to explain that the authors had provided context to the commonly used cutoff level for fibrinogen. “A rational conclusion from this study would be if the patient has an ongoing coagulopathy, the goal should be to at least increase their fibrinogen level to 100 mg/dL. I think that’s pretty much been the standard, interestingly. As far as I know, for decades that’s the cutoff we’ve been using if someone bleeds, but there was a dearth of data to support it. This tends to support what we practice and suggests we need to do more investigation and that perhaps even higher levels are important.”

Moore added that the authors’ research comes at a time when sharp differences have emerged in trauma care. The common practice in Western Europe now is to treat trauma-related coagulopathy with fibrinogen concentrates first, then resort to platelet or plasma products, whereas in the U.S. the standard of care is to administer plasma products initially, then move to fibrinogen products if the coagulopathy persists. Trials comparing these strategies are underway.

As evidence about trauma-related coagulopathies and treatments builds, both Shulman and Moore encouraged laboratorians to collaborate with trauma teams on best practices and continue to provide fast turnaround times on coagulation markers, including fibrinogen.