The Changing Landscape of Trauma Care, Part 1

Fall-Related Trauma

Falls are the most common cause of fatal and nonfatal injury in patients over age 65 years.¹⁵ Most fall injuries occur at home and during the winter months, and tend to be from ground level.¹⁶ Although most result in only minor trauma, many cause significant injuries requiring hospitalization. In 2006, Stevens et al¹⁷ estimated that both fatal and nonfatal falls in the elderly accounted for almost $20 billion in direct medical costs.

Motor Vehicle Collisions

Motor vehicle collisions/pedestrian struck are the second most significant causes of fatal and nonfatal injury in elderly patients. Older drivers who are hospitalized following an MVC have significantly longer hospital lengths of stay and an overall higher mortality rate.¹⁶ Elderly patients are more likely to be victims of “pedestrian-struck-by-vehicle” due to their decreased visual and auditory acuity, reduced reaction time, slower movement, and confusion.

Suicide

Suicide is the third leading cause of injury-related death for those aged 65 years and older.¹⁵ Risk factors for suicide in the elderly population include psychiatric disorders, particularly depression; medical conditions, especially cancer or chronic lung disease; moderate-to-large alcohol use; and social isolation. Changes in behavior, such as altering a will, new preoccupation with religion, or giving away life possessions, may be warning signs of impending suicide.

Novel Oral Anticoagulants

Many people, both old and young, are taking oral anticoagulants for various conditions. Warfarin has traditionally been the medication of choice, with readily available reversal agents, if needed. However, the development of NOACs, which antagonize activity of a single step in the coagulation cascade, has presented trauma care providers with a new challenge in achieving hemostasis. The NOACs include a direct thrombin inhibitor (dabigatran), and the Factor Xa (FXa) inhibitors (apixaban, edoxaban, and rivaroxaban). These NOACs have been shown to be as effective as traditional vitamin K antagonists (warfarin) with a comparable or lower spontaneous risk of bleeding. Along with an acceptable safety profile, these drugs cause significantly less drug and food interactions and are easier to dose, with no need for monitoring levels.¹⁸ Since the arrival of the first NOAC dabigatran in 2010, use of these drugs has continued to increase, and are becoming more popular in the treatment of venous thromboembolism in younger patients as well. A study by Desai et al¹⁹ examining newly initiated anticoagulation for AF between 2010 and 2013 found that 62% of all new anticoagulant prescriptions were for NOACs.

Hemostasis Challenges

Because of the lack of reversal agents or antidotes available, the NOACs present a unique challenge and major concern when anticoagulation properties must be reversed quickly. Among the NOACs, dabigatran is the only NOAC that is 35% protein bound and can be effectively cleared by hemodialysis (HD). Rivaroxaban and apixaban, in contrast, are highly protein bound (95% and 87%, respectively), which renders HD ineffective for clearance. Even for dabigatran, though HD may be a treatment option in the presence of potentially life-threatening bleeding associated with dabigatran alone, this is only a possibility if the patient’s hemodynamics can tolerate HD.

Extrapolating from experience with warfarin-associated bleeding, the use of FFP, PCC, and recombinant activated factor VII for NOAC-associated bleeding has been proposed and attempted.²⁰ Though FFP may be necessary to restore circulating blood volume as part of a massive transfusion protocol in a patient with NOAC-associated hemorrhage, it is generally not a reasonable sole strategy for reversal of NOACs because the coagulation factors in FFP are not present in high enough concentrations to be effective.¹⁸

Prothrombin Complex Concentrates

Three- and Four-Factor PCCs. Four-factor PCC (4F-PCC), which became available for use in the United States in April 2013, contains concentrated amounts of all four of the vitamin K dependent factors (II, VII, IX, and X), as well as proteins C and S. Three-factor PCC (3F-PCC) does not contain significant levels of factor VII,²⁰ and preclinical studies on its efficacy in reversing NOACs have not been consistent.

Early studies using animal models showed promising results for both 3F-PCC and 4F-PCC in correcting derangements in laboratory coagulation markers as well as observed bleeding time.^21-23 However, other animal studies failed to demonstrate an improvement in observed bleeding time or volume despite full or partial correction of coagulation studies after PCC.^24,25 In human studies, PCC has been observed to correct some laboratory parameters of coagulation, but not others.^26,27 Thus far, these studies have been limited to healthy volunteers without active bleeding and have been largely ex vivo and in vitro studies, so it is difficult to determine if the demonstrated correction of coagulation studies translates into clinical benefit. Both 3F-PCC and 4F-PCC have shown promise, though studies with 4F-PCC have yielded more consistent results.^26,27Activated PCC. Activated PCC (aPCC), which contains the same vitamin K dependent factors (factors II, VII, IX, X) with some in their activated form, has shown similar results. In fact, ex vivo and in vitro studies thus far seem to suggest that aPCC is more effective than PCC in correcting coagulation test parameters, as well as thrombin generation indices.^28-31 However, an aPCC has also been demonstrated to be more procoagulant and, thus, may increase the risk of thrombotic complications.³²