PHILADELPHIA – Antihypertension drugs may have a protective effect in obese trauma victims, while a better understanding of how obesity influences blood clotting may help trauma surgeons target treatment more effectively, according to early results from two trials involving obese patients.
“With the growing incidence of obesity, coupled with the increased incidence of trauma injury worldwide, elucidating the intimate associations between these two disease states is critical,” Dr. Lucy Kornblith of the University of California, San Francisco, said, reporting on a prospective analysis that determined that obese trauma victims have clotting properties superior to normal patients.
In another paper, investigators at the Washington University, St. Louis evaluated obese trauma victims who took ACE inhibitors or angiotensin receptor blocker (ARB) drugs before injury. “Obese patients who were not on ACE inhibitors or ARB drugs did develop organ failure, while those obese patients who took those medications did not,” Dr. Robert D. Winfield reported at the annual meeting of the American Association for the Surgery of Trauma.
Dr. Robert D. Winfield
The Washington University trial involved 1,932 patients, 94 of whom took the hypertension drugs and had body mass index (BMI) data available, a group that included 55 obese individuals. Obese subjects on the drugs had Marshall Multiple Organ Dysfunction and Denver-2 Postinjury Multiple Organ Failure trauma scores similar to nonobese patients either taking or not taking the drugs, 5.83 and 2.45, respectively, Dr. Winfield said.
He explained the drugs may enable cells in obese individuals to express more CD47, a cell surface marker that plays a role in monocyte maturation. “What we see in those obese patients taking ACE-I or ARB preinjury is not a perfect response, but it is better,” he said. “We see more cells expressing CD47, and as a result, we see improved cell maturation and tracking and the ability to battle, in particular, secondary insults.”
The next step involves animal research to see if ACE-I and ARB use before and after injury can modulate the immune response, which Washington University and the American College of Surgeons are funding, according to Dr. Winfield.
The UCSF study did not draw any definitive conclusion of the overall benefits or drawbacks of hypercoagulability in the obese after injury, Dr. Kornblith said, although it did suggest one significant deleterious effect in multivariate analysis. “We found that for every 5 kg/m2 increase in BMI, there was an 85% increase in the odds of developing a clinically significant thromboembolic complication,” she said.
The study, using data from “Inflammation and the Host Response to Injury” database, evaluated 377 patients with an average BMI of 25.8 kg/m2, about a quarter of whom were obese (average BMI 33 kg/m2). Obese patients had higher admission platelet counts (302.69 x 103mcL vs. 268.58 x 103mcL) and factor IX (134% vs. 119% activity), and lower D-dimer counts (1.88 vs. 4.00 mc/mL) than did normal weight patients. Thromboelastography measured stronger clot and higher levels of functional fibrinogen on admission in obese patients. These findings of hypercoagulability in the obese patients existed out to 24-120 hours after injury.
Dr. Kornblith acknowledged several limitations to the study. “We do not do a screening duplex ultrasound for DVTs [deep vein thromboses] at our institution,” she said. “There may also be a much higher incidence of nonclinically significant clots in this population; however, based on this, if anything, our numbers are really an underestimate reflecting only those that were clinically significant.”
More work needs to be done, Dr. Kornblith noted. “It is known that excess adipose tissue is far from inert, and it plays a cardinal role in the biology and physiology of obesity,” she said. “Untangling the complex interaction of inflammation, coagulation, and injury will really help contribute to a better understanding of the clinical outcome differences seen in obese patients after injury and may help with targeted treatment of this at-risk group.”
Dr. Kornblith and Dr. Winfield reported having no financial disclosures.