What Gets Lost When Autopsies Aren’t Done? Not Just Cause of Death

Medical autopsies are on the decline.

This well-documented trend stretches all the way back to the early 1970s, when, according to the Centers for Disease Control and Prevention, the medical autopsy rate, which is the number of autopsies per number of hospital deaths, began steadily decreasing. In the 1950s, hospital autopsy rates stood at about 50%, meaning half of all people who died in the hospital received an autopsy. By 1972, that rate had dropped to 19.1%. Today, pathologists estimate the rate to be as low as 5%.

That is the lowest autopsy rate on record—a metric that is concerning to some pathologists.

“The numbers have fallen drastically. It breaks my heart,” says Harry Sanchez, MD, assistant professor and director of Autopsy Services in the Department of Pathology at Yale School of Medicine (YSM). “It would be different if the numbers had fallen drastically and there was no data to suggest that it didn’t matter. The data that’s out there suggests that it does matter.”

It’s not just pathologists, such as Sanchez, who wish autopsies were being done more often. Clinicians who provide care to patients in their final days still see value in this procedure, and researchers can obtain important resources from autopsies that they can’t get elsewhere. Autopsies provide information beyond a person’s cause of death, including insights that can prove meaningful to hospitals, physicians, researchers, and patients’ families.

There are a number of possible explanations for the declining autopsy rate in the United States. Prior to 1971, the Joint Commission, which establishes guidelines for medical care and practices, required hospitals to perform autopsies on 20-25% of patients who died while hospitalized as one of the criteria for accreditation, but that’s no longer the case. As a result, many hospitals in the United States have abandoned the practice altogether.

Other factors may also contribute to the declining rate, such as physicians’ reluctance to approach patients’ families about an autopsy and take the time to obtain informed consent, or fear of litigation if the autopsy finds something that the clinical team missed while caring for the patient, Sanchez says.

There also are advances in imaging technologies such as CT scans, MRIs, and ultrasounds that may lead physicians to think they have accurately assessed what led to a patient’s death without the need for an autopsy.

“There are assumptions we make based on lab tests and imaging. Most of the time we’re right,” says Shyoko Honiden, MD, MSc, associate professor of medicine (pulmonary, critical care & sleep medicine) at YSM and director of the medical intensive care unit (MICU) at Yale New Haven Hospital. “But there are things that we don’t know for sure. … Some of the final pieces of the puzzle that help us understand what happened farther upstream—what actually was the triggering event for a person’s demise—can really only be found with the autopsy.”

Despite their declining frequency, autopsies can provide clinically relevant information that physicians find helpful in their treatment of the living.

In 2020, Sanchez and Honiden began holding Zoom meetings between the pathology department and clinical care teams from the MICU to discuss preliminary autopsy findings. Normally, the final autopsy report would take weeks or months to reach the team that cared for the patient. But through these virtual meetings, they were able to discuss preliminary findings right away and share questions and feedback with each other. These meetings, said Sanchez, were great for both groups.

“We had immediate access to the people who actually took care of the patients and could ask them questions about issues that weren’t clear to us,” he says. “We were able to show them what we had, and we could put it into context.”

From Honiden’s perspective, these collaborations were not only beneficial for affirming diagnoses or raising new questions, but for the educational component of the process as well.

“For the medical students, interns, residents, fellows, attendings, it has been a super valuable experience to be able to really see the care through from the day [the patient] arrives into our unit to the day they expire,” she says. “We spend time and resources in the care of our patients. When they die, despite our best efforts, we turn the page and move on to care for the next patient. Being able to collaborate with our pathology department and following through on the autopsy findings has given our providers closure as well.”

There are also instances where the autopsy would turn up unexpected findings, which Sanchez says accounts for about 15-20% of the autopsies he performs. He’s seen cases such as undiagnosed tumors in patients who died of other complications, undiagnosed COVID-19, and lung masses that turned out to be fungal infections, microscopic tumors, and rare inflammatory disease. Cases such as these can be valuable in preparing clinicians for any similar cases in the future.

“There are definitely some things that we have been able to confirm because of the autopsy finding, completely unexpected findings which we then are able to have in our differential diagnosis armamentarium for the next patient that comes with a similar presentation,” Honiden says. “There is a wealth of information that we glean through an autopsy process that can help inform future care.”

Historically, autopsies have proved essential in understanding the mechanisms and pathology of various medical conditions and infectious diseases.

For example, early in the COVID-19 pandemic when cell culture and animal models were not yet available, autopsies were invaluable in understanding the pathology of the disease.

“[COVID-19] had just appeared, and nobody really knew what to expect; autopsies were a big part of defining the illness,” says Sanchez. “Once people understood what the pathologic changes were and started figuring out what the actual physiology of the disease was and putting together a rational plan for therapy, therapy was modified.”

In the early stages of the pandemic, autopsy results revealed to researchers such conditions as blood clots in the veins of COVID-19 patients, which prompted further investigation into blood clotting treatments and helped scientists learn more about the disease. Autopsy results also showed that COVID-19 affected multiple organs apart from the lungs, and found evidence of the virus in multiple sites several months after initial infection.

Autopsies have also been used to uncover information in a variety of other medical contexts such as appendicitis, heart disease, infectious diseases like tuberculosis, and even cancer.

For example, in 1948, the Framingham Heart Study followed participants in Framingham, Massachusetts, and collected health data on them until they died. After their deaths, autopsy results showed that conditions such as smoking, high cholesterol levels, and high blood pressure were risk factors for coronary artery disease, which led to the development of new clinical strategies to modify these factors.

Today, autopsies are being used to uncover important information about the nature of metastatic cancers. Researchers at Memorial Sloan Kettering Cancer Center and Johns Hopkins have research autopsy programs where they are able to compare a patient’s original tumor with metastasized tumor to look for molecular differences that caused the tumor to metastasize or become resistant to chemotherapy. Obtaining metastatic tumor tissue is particularly challenging without an autopsy, Sanchez says.

“If you have a tumor that has spread widely, there’s no reason for a surgeon to go in and take that out,” he says. “You really can’t get certain types of tissue any other way except for after death, so this opens up avenues and research that just wouldn’t be available in other ways.”

Realizing the incredible value of such human tissue, Sanchez and Marcello DiStasio, MD, PhD, assistant professor of pathology, founded the Yale Legacy Tissue Donation Program last July as a way to provide patients with the means to make meaningful contributions to science at the end of their lives, as well as expand scientific opportunities for Yale’s biomedical researchers.

“Often these [patients] are older or have diagnoses. They’re really motivated to help in some way but they can’t be organ donors or tissue donors in the usual sense, but they’re an ideal candidate for donating for research,” says Sanchez. “That’s great for the research folks, and that’s great for these people who are motivated to donate.”

Because human tissue is so hard to obtain, researchers often study such animal models as mice, or perform cell cultures. But these models have flaws, says Ed Manning, MD, PhD, assistant professor of medicine (pulmonary).

Manning studies the remodeling of the pulmonary vasculature system, aiming to understand why and how lung performance changes with age. In mouse models, he has found that pulmonary arteries can stiffen, which may be a factor in why lung function decreases with age. Manning has been experimenting with using medication and exercise to prevent the stiffening but, as he says, “Who really cares if we make mice live longer?”

“That’s where human tissue comes into play, because if you can validate those findings in human tissue, then it’s not just about treating mice, it’s about seeing if this can translate [to care for human patients],” he adds.

The Legacy program provides an option for patients to provide tissue as a “gift” after their death, which proves incredibly valuable to researchers such as Manning. What’s called a “rapid autopsy” would deliver a tissue sample about 24 - 72 hours after the patient’s death. While the sample still has value as an intact human tissue, the cells have all died by that point. But with the Legacy program, tissue samples are obtained less than 12 hours after the patient’s death, improving the odds of recovering live cells and intact nucleic acids.

In part because of the Legacy program, as well as through the efforts of his mentor, George Tellides, MD, PhD, professor of surgery (cardiac), Manning has been able to obtain more than 100 pulmonary arteries for his research. He recently found that the human pulmonary artery does indeed stiffen with age, which is associated with decline in lung function.

“Without [these samples], my research would have really been confined to animals, and while interesting and potentially meaningful, the question would always be, does this apply to humans?” Manning says. “I can’t even put into words how this has opened doors to new ideas investigating how the human body works … and how we’re able to learn how to stop this and help people live longer lives while breathing better and lengthening the healthspan.”

Since starting the Legacy Tissue Donation Program last year, Sanchez and DiStasio have been able to provide tissue samples to labs at Yale, supplying everything from bone marrow tissue to eye tissue. The diversity of tissue that the Legacy program provides sets Yale apart.

“A lot of these research autopsy programs in the U.S are mostly driven by one particular disease,” says DiStasio, such as programs that might only study a certain kind of cancer. “We are really trying to build our program as a core resource for Yale, and I think that has huge benefits for researchers but also patients … Any request that I can fulfill from any given researcher, we try to fulfill, and so it enables a much broader set of studies from any given patient’s donation.”

DiStasio himself has been using these tissue samples to study both the immunology of the brain, as well as macular degeneration, and potential ways to reverse it.

“The generosity of the donors to the Legacy program in letting their tissues be used means we have access to human eye samples which we would not otherwise have,” DiStasio says.

Beyond creating new biomedical research opportunities, autopsies can also be used to inform quality-control metrics at hospitals.

For instance, Yale New Haven Hospital uses autopsy results to develop quality-assurance data by comparing clinical diagnoses with autopsy diagnoses to see if they match. The autopsy rate at YNHH is the highest in the state of Connecticut—Sanchez estimates about 10-15%. In other hospitals across the United States performing fewer autopsies, sufficient quality control data can be difficult to generate.

“If a particular hospital has a 0% autopsy rate, what does that say about the hospital? It would mean that they don’t really know why their patients are dying. They may think they know, but there’s no quality program to verify,” says John Sinard, MD, PhD, professor of pathology and of ophthalmology & visual science.

Sanchez adds that autopsies are needed to reduce the rate of medical errors in general. In 2000, the National Academy of Medicine (then called the Institute of Medicine) published a book called To Err is Human, where they discussed the rate of medical errors in the United States, estimating that tens of thousands of deaths occurred annually due to medical errors. In 2015, they released another publication called Improving Diagnosis in Health Care, where they outlined that in order to decrease the rate of medical errors, there needed to be a reliable way to measure them, which included autopsy.

But in order to get accurate error data from autopsies, Sanchez says, enough post-mortems need to be performed. “It really doesn’t do any good to just cherry-pick,” he notes. “If your goal is to find out what the rate of error is, then you need a statistically large enough sample”

It’s not just clinicians, researchers, and hospitals that gain meaningful information from autopsies. Autopsy results can be important for the families of the deceased as well. For one, family members may want to know if there is any risk of inheriting medical conditions that could have caused or contributed to the death and if the condition is something that could run in the family.

“[Autopsy] definitely can have an impact, not just informationally as closure, but also for the living relatives in terms of what information they need to know for their own health and care moving forward,” says Honiden.

Family members may also experience some guilt after the death of a loved one, and an autopsy can provide answers about what really happened.

“A lot of times families are looking for assurance that really they could have done nothing to prevent death,” says Sinard. “Finding out that no, actually there’s nothing you could have done can be very reassuring.”