Las Vegas—When choosing the best treatment for trauma- or surgery-related bleeding, clinicians should know their pathophysiology and the pros and cons of each agent, according to a presentation at the American Society of Health-System Pharmacists 2012 Midyear Clinical Meeting.
“It amazes me how frequently I bring up the topic during rounds and find clinicians are unfamiliar with many of the causes, mechanisms and treatments for massive bleeding,” said presenter Rob MacLaren, PharmD, an associate professor at the University of Colorado School of Pharmacy, in Aurora.
The primary goal of treating trauma-related bleeding is to prevent the depletion of thrombin, Dr. MacLaren explained. “Trauma and shock lead to a release of large amounts of thrombin, which then binds to thrombomodulin, which is actually an anticoagulant,” he said. “On top of this, trauma patients often receive large volumes of resuscitative fluids that further dilute endogenous clotting factors and increase bleeding.”
Given this and other risks associated with large volumes of resuscitative fluids, Dr. MacLaren recommended administering 2 L of crystalloid fluids “as soon as you can” and observing the patient’s response. If their vital signs do not quickly return to normal, he recommended adding more crystalloid fluid and considering the patient for transfusion and surgery.
Before administering blood products or drugs, clinicians should ensure that other risk factors for mortality are under control. Most critically, minimize the risk for hypothermia, acidosis and dilution, he said. Because patients with this “lethal triad” have a 95% risk for death (Crit Care 2006;10:222), trying to control these should be a priority, Dr. MacLaren said.
Blood Products Are ‘Not Benign’
Once these risk factors are evaluated and, ideally, controlled, clinicians can consider transfusion of a blood product (Table 1). However, Dr. MacLaren said this decision should not be made lightly. “All blood products are associated with a risk of acute lung injury, infections and organ failure and are, therefore, not benign,” he said.
Bearing these complications in mind, each blood product has its advantages and limitations, Dr. MacLaren said. For example, cryoprecipitate increases fibrinogen levels but does not reduce a patient’s international normalized ratio (INR); platelets and red blood cells can worsen the immune response; and prothrombin complex concentrates and fresh frozen plasma (FFP) can lower INR levels but not below the goal of 1.5 prothrombin time. “Furthermore, large amounts of FFP may contribute to the development of encephalopathy and cerebral edema,” he noted.
Dr. MacLaren discussed the features of several of the newer pharmacologic agents that have joined the mainstays for treatment of hemorrhage (Table 2). “Recombinant factors VIIa [rFVIIa] and VIIIa [rFVIIIa] are appealing because they work downstream and cause a thrombin burst,” he explained. “Therefore, they are more specific to the site of injury, and they don’t involve all the systemic activity of clotting factors and platelets that the procoagulant blood products need.”
Although rFVIIa reduces the use of blood products and lowers the risk for acute respiratory distress syndrome, possibly a result of the reduced use of blood products, Dr. MacLaren noted, it does not actually reduce the incidence of mortality (Ann Intern Med 2011;154:529-540). Similarly, in the cardiac surgery setting, rFVIIa does not reduce mortality rates but increases the rate of thromboembolic events. “This agent should only be used for refractory bleeding,” he said.
Among the antifibrinolytics, tranexamic acid (TA) is a promising agent, he said, and data indicate that it significantly reduces the risk for trauma-related death (Lancet 2010;376:23-32; Lancet 2011;377:1096-1100). However, to prevent one death, 120 patients need to be treated, Dr. MacLaren said. He noted that TA might have greater utility in the surgical setting, where it and ×-aminocaproic acid (EACA) can be used interchangeably to prevent and treat massive blood loss.
The myriad considerations involved in choosing a treatment for these types of bleeds make the task a tricky one, commented Asad Patanwala, PharmD, an assistant professor at the University of Arizona’s College of Pharmacy, in Tucson. However, he said advances in thromboelastography (TEG)—a method of testing clotting efficiency that is used primarily in the surgery setting—may yield better decision making. “TEG-directed therapy may allow for specific coagulation abnormalities to be targeted,” Dr. Patanwala told Pharmacy Practice News. “It could allow clinicians to tailor therapies, rather than using a one-size-fits-all approach, but better evidence is needed before it can be routinely used in settings such as trauma.”
Drs. MacLaren and Patanwala reported no relevant financial conflicts of interest.