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Friday, April 18, 2014

Tranexamic acid--why you may be less likely to bleed to death in Britain than the U.S.

The other day at an interdisciplinary rounds meeting at the hospital, one of our nurses who is also an emergency medical technician mentioned that in Britain injured patients receive tranexamic acid before arriving at the hospital because it reduces death from bleeding. “What’s that?” I said. I kind of barely remembered hearing this medication’s name associated with the treatment of a rare disease, but not treatment of trauma. So I was guessing that this was some drug that was invented long ago which had been found to be quite effective in other countries, but has not been really optimally used in the U.S. because it is generic and therefore unlikely to make drug companies money.

Bingo.

Here’s the story, as far as I can determine.

Tranexamic acid is a relatively simple cyclic molecule that blocks the fibrinolytic process, that is, the natural breakdown of blood clots in the body. In the setting of any injury, especially severe ones, fibrinolysis is intensified, leading to a condition of excess bleeding in trauma victims. This is hardly ideal, and tranexamic acid can help reverse this. It also appears to have an effect on reducing inflammation, which may be even more significant.

There have been a couple of major studies in the last 3 years showing significantly better outcomes in patients who have traumatic injury and who are treated with tranexamic acid intravenously soon after injury. The most recent study, published in the Archives of Surgery, looked at 896 patients injured in the military from registries in the UK and the U.S. and identified the subset treated with tranexamic acid. Although this group was generally more severely injured, the mortality rate was significantly lower, 6.5% lower, than the group that had not received the drug. In very seriously injured patients, those who received massive transfusion of blood products, the difference in survival was nearly 14%.

It is not often that we see an effect this powerful, especially in a group like this who are healthy and will likely have long and productive lives after being saved. An earlier study, published in 2011 in the Lancet titled CRASH-2, showed similar results in civilian trauma victims, with a double-blind, prospective design. The Cochrane Collaboration, a group of researchers who review randomized controlled trials, concluded that tranexamic acid was safe and effective in reducing mortality in trauma patients without increasing adverse events.

So maybe it’s actually very expensive, then. I called our hospital pharmacy to ask about that. Apparently a gram of it costs about $44. The usual protocol for trauma is 1 gram intravenously right away and then another gram over the next 8 hours. So $88 times 100 equals $8,800 to save 6.5 lives (using the data from the military study), or $1,353 per life saved. That’s pretty cheap. And since it probably reduces the severity of illness in the rest of the patients treated, it may end up reducing overall treatment costs.

Presently the only FDA (Food and Drug Administration) approved indication for this drug in the U.S. is an oral formulation to be used for women with heavy periods and intravenously for prevention of dental bleeding in hemophiliacs. It is also used off-label to reduce transfusion requirements in total joint surgeries (that’s why we have it in our pharmacy), also in some places for prostate surgery, general surgery, gastrointestinal hemorrhage, bleeding around pregnancy and delivery and bleeding within the eye. It reduces the frequency of attacks of swelling in a condition called hereditary angioedema, which is rare, and was why I had even heard of it in the past. It has been available over the counter for years in Europe, marketed for heavy menstrual bleeding. The injectable formulation is also on the World Health Organization’s list of 350 essential medicines which are considered safe and effective and necessary worldwide.

So what are its side effects? It may increase the risk of blood clots in the legs and lungs, but studies have shown this to be far less of an issue than one might guess, and it looks like the lives saved far outweigh this risk. The CRASH-2 study showed that there might be a slight risk of increasing mortality if it was given to trauma patients more than 3 hours after their injury.

Why is it not FDA approved for reduction of bleeding in trauma and other similar situations for which there is ample evidence of safety and efficacy? The FDA approves drugs and devices when approval is requested, and usually the drug or device manufacturers who stand to make money from an FDA approved indication are the ones to make the request. I suspect there has been no request for approval for these other indications. Just because it is not FDA approved to reduce bleeding in trauma and surgery doesn’t mean it can’t be used, but physicians have a certain hesitance to use unfamiliar drugs off-label.

So the story of tranexamic acid is another excellent example of how simpler, cheaper and sometimes more effective treatments are not being widely used in the U.S., even though our patients may receive exorbitantly expensive medications and treatments of dubious or minimal benefit. This is because we allow powerful pharmaceutical companies to inform our practice. Sometimes this actually works, when companies produce groundbreaking innovations and encourage us to adopt them. It is unlikely, though, to help us find creative uses for inexpensive drugs that have been around a long time. This dynamic may mean that 6 or so people of the 100 who are probably just now being involved in accidents with bleeding will die when they would not have if use of this drug part of our routine practice.

Janice Boughton, MD, ACP Member, practiced in the Seattle area for four years and in rural Idaho for 17 years before deciding to take a few years off to see more places, learn more about medicine and increase her knowledge base and perspective by practicing hospital and primary care medicine as a locum tenens physician. She lives in Idaho when not traveling. Disturbed by various aspects of the practice of medicine that make no sense and concerned about the cost of providing health care to every American, she blogs at Why is American Health Care So Expensive?, where this post originally appeared.

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Blog log

Members of the American College of Physicians contribute posts from their own sites to ACP Internistand ACP Hospitalist. Contributors include:

Albert Fuchs, MD
Albert Fuchs, MD, FACP, graduated from the University of California, Los Angeles School of Medicine, where he also did his internal medicine training. Certified by the American Board of Internal Medicine, Dr. Fuchs spent three years as a full-time faculty member at UCLA School of Medicine before opening his private practice in Beverly Hills in 2000.

And Thus, It Begins
Amanda Xi, ACP Medical Student Member, is a first-year medical student at the OUWB School of Medicine, charter class of 2015, in Rochester, Mich., from which she which chronicles her journey through medical training from day 1 of medical school.

Auscultation
Ira S. Nash, MD, FACP, is the senior vice president and executive director of the North Shore-LIJ Medical Group, and a professor of Cardiology and Population Health at Hofstra North Shore-LIJ School of Medicine. He is Board Certified in Internal Medicine and Cardiovascular Diseases and was in the private practice of cardiology before joining the full-time faculty of Massachusetts General Hospital.

Zackary Berger
Zackary Berger, MD, ACP Member, is a primary care doctor and general internist in the Division of General Internal Medicine at Johns Hopkins. His research interests include doctor-patient communication, bioethics, and systematic reviews.

Controversies in Hospital Infection Prevention
Run by three ACP Fellows, this blog ponders vexing issues in infection prevention and control, inside and outside the hospital. Daniel J Diekema, MD, FACP, practices infectious diseases, clinical microbiology, and hospital epidemiology in Iowa City, Iowa, splitting time between seeing patients with infectious diseases, diagnosing infections in the microbiology laboratory, and trying to prevent infections in the hospital. Michael B. Edmond, MD, FACP, is a hospital epidemiologist in Richmond, Va., with a focus on understanding why infections occur in the hospital and ways to prevent these infections, and sees patients in the inpatient and outpatient settings. Eli N. Perencevich, MD, ACP Member, is an infectious disease physician and epidemiologist in Iowa City, Iowa, who studies methods to halt the spread of resistant bacteria in our hospitals (including novel ways to get everyone to wash their hands).

db's Medical Rants
Robert M. Centor, MD, FACP, contributes short essays contemplating medicine and the health care system.

Suneel Dhand, MD, ACP Member
Suneel Dhand, MD, ACP Member, is a practicing physician in Massachusetts. He has published numerous articles in clinical medicine, covering a wide range of specialty areas including; pulmonology, cardiology, endocrinology, hematology, and infectious disease. He has also authored chapters in the prestigious "5-Minute Clinical Consult" medical textbook. His other clinical interests include quality improvement, hospital safety, hospital utilization, and the use of technology in health care.

DrDialogue
Juliet K. Mavromatis, MD, FACP, provides a conversation about health topics for patients and health professionals.

Dr. Mintz' Blog
Matthew Mintz, MD, FACP, has practiced internal medicine for more than a decade and is an Associate Professor of Medicine at an academic medical center on the East Coast. His time is split between teaching medical students and residents, and caring for patients.

Everything Health
Toni Brayer, MD, FACP, blogs about the rapid changes in science, medicine, health and healing in the 21st century.

FutureDocs
Vineet Arora, MD, FACP, is Associate Program Director for the Internal Medicine Residency and Assistant Dean of Scholarship & Discovery at the Pritzker School of Medicine for the University of Chicago. Her education and research focus is on resident duty hours, patient handoffs, medical professionalism, and quality of hospital care. She is also an academic hospitalist.

Glass Hospital
John H. Schumann, MD, FACP, provides transparency on the workings of medical practice and the complexities of hospital care, illuminates the emotional and cognitive aspects of caregiving and decision-making from the perspective of an active primary care physician, and offers behind-the-scenes portraits of hospital sanctums and the people who inhabit them.

Gut Check
Ryan Madanick, MD, ACP Member, is a gastroenterologist at the University of North Carolina School of Medicine, and the Program Director for the GI & Hepatology Fellowship Program. He specializes in diseases of the esophagus, with a strong interest in the diagnosis and treatment of patients who have difficult-to-manage esophageal problems such as refractory GERD, heartburn, and chest pain.

I'm dok
Mike Aref, MD, PhD, FACP, is an academic hospitalist with an interest in basic and clinical science and education, with interests in noninvasive monitoring and diagnostic testing using novel bedside imaging modalities, diagnostic reasoning, medical informatics, new medical education modalities, pre-code/code management, palliative care, patient-physician communication, quality improvement, and quantitative biomedical imaging.

Informatics Professor
William Hersh, MD, FACP, Professor and Chair, Department of Medical Informatics & Clinical Epidemiology, Oregon Health & Science University, posts his thoughts on various topics related to biomedical and health informatics.

David Katz, MD
David L. Katz, MD, MPH, FACP, is an internationally renowned authority on nutrition, weight management, and the prevention of chronic disease, and an internationally recognized leader in integrative medicine and patient-centered care.

Just Oncology
Richard Just, MD, ACP Member, has 36 years in clinical practice of hematology and medical oncology. His blog is a joint publication with Gregg Masters, MPH.

KevinMD
Kevin Pho, MD, ACP Member, offers one of the Web's definitive sites for influential health commentary.

MD Whistleblower
Michael Kirsch, MD, FACP, addresses the joys and challenges of medical practice, including controversies in the doctor-patient relationship, medical ethics and measuring medical quality. When he's not writing, he's performing colonoscopies.

Medical Lessons
Elaine Schattner, MD, FACP, shares her ideas on education, ethics in medicine, health care news and culture. Her views on medicine are informed by her past experiences in caring for patients, as a researcher in cancer immunology, and as a patient who's had breast cancer.

Mired in MedEd
Alexander M. Djuricich, MD, FACP, is the Associate Dean for Continuing Medical Education (CME), and a Program Director in Medicine-Pediatrics at the Indiana University School of Medicine in Indianapolis, where he blogs about medical education.

More Musings
Rob Lamberts, MD, ACP Member, a med-peds and general practice internist, returns with "volume 2" of his personal musings about medicine, life, armadillos and Sasquatch at More Musings (of a Distractible Kind).

Prescriptions
David M. Sack, MD, FACP, practices general gastroenterology at a small community hospital in Connecticut. His blog is a series of musings on medicine, medical care, the health care system and medical ethics, in no particular order.

Reflections of a Grady Doctor
Kimberly Manning, MD, FACP, reflects on the personal side of being a doctor in a community hospital in Atlanta.

The Blog of Paul Sufka
Paul Sufka, MD, ACP Member, is a board certified rheumatologist in St. Paul, Minn. He was a chief resident in internal medicine with the University of Minnesota and then completed his fellowship training in rheumatology in June 2011 at the University of Minnesota Department of Rheumatology. His interests include the use of technology in medicine.

Technology in (Medical) Education
Neil Mehta, MBBS, MS, FACP, is interested in use of technology in education, social media and networking, practice management and evidence-based medicine tools, personal information and knowledge management.

Peter A. Lipson, MD
Peter A. Lipson, MD, ACP Member, is a practicing internist and teaching physician in Southeast Michigan. The blog, which has been around in various forms since 2007, offers musings on the intersection of science, medicine, and culture.

Why is American Health Care So Expensive?
Janice Boughton, MD, FACP, practiced internal medicine for 20 years before adopting a career in hospital and primary care medicine as a locum tenens physician. She lives in Idaho when not traveling.

World's Best Site
Daniel Ginsberg, MD, FACP, is an internal medicine physician who has avidly applied computers to medicine since 1986, when he first wrote medically oriented computer programs. He is in practice in Tacoma, Washington.

Other blogs of note:

American Journal of Medicine
Also known as the Green Journal, the American Journal of Medicine publishes original clinical articles of interest to physicians in internal medicine and its subspecialities, both in academia and community-based practice.

Clinical Correlations
A collaborative medical blog started by Neil Shapiro, MD, ACP Member, associate program director at New York University Medical Center's internal medicine residency program. Faculty, residents and students contribute case studies, mystery quizzes, news, commentary and more.

Interact MD
Michael Benjamin, MD, ACP member, doesn't accept industry money so he can create an independent, clinician-reviewed space on the Internet for physicians to report and comment on the medical news of the day.

PLoS Blog
The Public Library of Science's open access materials include a blog.

White Coat Rants
One of the most popular anonymous blogs written by an emergency room physician.

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