The Changing Landscape of Trauma Care, Part 1

Recombinant Activated Factor VII

Recombinant activated factor VII has shown less promise than PCC or aPCC in the reversal of NOAC-associated bleeding. Additionally, similar to aPCC, it may increase the risk of thrombosis.^20,33

Monoclonal Antibody Agent

In October 2015, the US Food and Drug Administration approved idarucizumab, a monoclonal antibody agent for the reversal of dabigatran. Idarucizumab has a binding affinity approximately 350 times higher than the binding affinity of dabigatran for thrombin with no demonstrated procoagulant effects.²⁰ To date, there are no commercially available antidotes or reversal agents for the FXa inhibitors, though two promising agents are in various phases of clinical trials. The first, andexanet alfa, is a modified, recombinant factor X which binds FXa inhibitors with high affinity. This agent has shown promising results in the reversal of apixaban and rivaroxaban.²⁰ The second is called aripazine (PER977) and has the potential to reverse unfractionated heparin, low molecular weight heparins, fondaparinux, FXa inhibitors, and thrombin inhibitors. Early in vivo human studies have been promising.¹⁸

Currently, there are no well-designed clinical studies examining the use of PCC for NOAC reversal in trauma. There are only a few published case reports, showing both successful and unsuccessful results, and a small retrospective series of only 18 patients specifically looking at both traumatic and spontaneous intracranial hemorrhage.^34-37 There are also no universally agreed upon published guidelines for the management of NOAC-associated bleeding in the absence of drug-specific reversal agents.

Penetrating Trauma

The United States leads all high-income nations in GSW mortality,³⁸ and its rate of firearm homicide is almost 20 times that of other high-income countries. In 2014, there were more than 33,000 firearm-related deaths in the United States, almost two-thirds of which were suicide-related.³⁸ These numbers represent 16.8% of all deaths from injury. For each fatal firearm injury, there were nearly two nonfatal firearm injuries (65,106) the same year.³⁹ Since 2001, the leading cause of death among black males aged 15 to 44 years has been firearm-related homicide. In 2015, that age demographic was lowered to include 10- to 14-year-old black males. In 2015, suicide by firearm was the second leading cause of death among white males over the age of 55 years and the third leading cause of death among white males aged 10 to 54 years.⁴⁰

Incidents of gun violence are on the rise. These incidents are becoming more frequent and more often fatal. In a retrospective review of their trauma registry, as well as county records, Sauaia et al⁴¹ examined trends of GSW severity and mortality in Denver, Colorado from 2000 to 2013. They noted the proportion of GSW admissions remained stable over time, but injury severity and mortality from GSWs increased significantly, contrary to mortality and survival trends for all other injury mechanisms.⁴¹

The increasing GSW severity and mortality trend is not unique to Denver. Many media sources in cities across the country have reported similar statistics obtained from their local police departments in the past year. Though gun violence is a subject that is in desperate need of prevention research, current legislation makes these studies challenging to undertake. In 1996, Congress passed the Dickey Amendment to the Omnibus Consolidated Appropriations Act for the 1997 fiscal year, which states that “none of the funds made available for injury prevention and control at the Centers for Disease Control and Prevention may be used to advocate or promote gun control.”^42,43 In the 2011 Consolidated Appropriations Act for the fiscal year 2012, this restriction was expanded to include the National Institutes of Health (NIH).^44,45 These measures largely explain the paucity of primary research in gun violence in the last two decades—despite the increasing role and costs gun violence contributes to the US health care system. Gun violence is an epidemic, and like all other epidemics in the United States, it requires government-funded research to help protect the people.⁴⁴

Conclusion

The last decade has seen some significant changes in trauma demographics in the United States. As the population of US men and women older than age 65 years continues to grow, trauma can no longer be considered a disease of young people. In addition to elderly men and women being more active than ever before, comorbid diseases place them at higher risk for complications and death following injury. For these reasons, many trauma triage algorithms now include age as an independent factor in activating a trauma alert. In addition to age, medications, and especially polypharmacy, can place patients at greater risk of injury and complications following trauma.

The last 10 years also has seen an increase in the number of patients on anticoagulants. The development of the NOACs further complicates the care of trauma patients taking these medications. Although designed to simplify care for patients and providers by minimizing bleeding risks and eliminating blood monitoring, there are only limited, and sometimes no reliable reversal agents available for NOACs, creating challenges when treating trauma patients who are on these medications. Finally, despite efforts by many individuals and groups, gun violence still remains a large and growing problem in the United States. Hopefully, continued efforts of national, state and local programs will begin to improve the current situation.