Severe hemorrhage kills, but we’ve learned a few things over the years about how to better help such patients. Earlier transfusions can improve their chances, and using fresh whole blood appears better than using only components.
Those discoveries are being combined in South Texas under a new program from the South Texas Blood & Tissue Center and local air-medical services. The Brothers in Arms program—the name a triple play on its military-derived concept, male-only donor pool, and blood drawn from the arm—uses specially tested cold stored whole blood from a select pool of donors and delivers it by helicopter to transfuse hemorrhaging civilians in the San Antonio area.
“Whole blood, and cold stored whole blood specifically, has always been an FDA-approved product line,” says Don Jenkins, MD, FACS, a clinical professor in the Division of Trauma and Emergency Surgery and the Betty and Bob Kelso Distinguished Chair in Burn and Trauma Surgery at the University of Texas Health Science Center at San Antonio. “But the way people thought about it was, if a blood bank invests in component therapy and breaking down the donation into its component parts, then why would you need the real deal, the whole 1:1:1? It turns out we were short-sighted.”
The Longer View
Rather, combat research showed military physicians that transfusing early, using whole blood rather than separate red cells, plasma, and/or platelets, is more effective for trauma victims with major blood loss. That led to the 75th Ranger Regiment’s pioneering O Low-Titer Whole Blood Program, which won the Army’s Greatest Innovation Award for 2017. Its results were promising enough to merit translation to the civilian world, and Jenkins later adapted the concept at the Mayo Clinic trauma center, which he directed. San Antonio leaders are now applying the idea more broadly.
“Implementing this program for civilian use will truly transform how emergency care can be administered on medical helicopters and significantly improve survival rates for trauma victims,” said Elizabeth Waltman, COO of the South Texas Blood & Tissue Center (STBTC), in a release announcing the program. “This is also the first step toward a longer-term solution for saving more lives in mass-casualty situations, especially if we are able to expand the program in the future to include emergency care provided by ambulance services.”
The blood is being delivered by five local HEMS providers, with 11 helicopters currently operating and seven more coming online by mid-April. The blood comes from Waltman’s organization, which collects it from specially tested O-positive male donors. The universal blood type commonly used for emergency transfusions is O-negative, but only about 7% of people have it. More than 30% are O-positive, making it much more widely available. STBTC is building a pool of committed O-positive male suppliers for the program. (Men’s blood typically has lower levels of certain antibodies that can cause adverse reactions among recipients, and the center’s sister blood-testing organization has developed a testing protocol to identify positive donors with low antibody levels.)
Positive blood isn’t typically used for transfusions because blood with a positive Rh factor, given to a woman who lacks it, can cause pregnancy problems. But when they crunched the numbers, Jenkins and his colleagues determined that represented a fairly minimal risk to a fairly small number of patients: Only about 15% of the white population and 7% of African-Americans are Rh-negative, and the chance of a pregnant woman developing problem antibodies if exposed to positive blood is only about 20%. Meanwhile, Jenkins says, the death rate of women of childbearing age who need massive transfusions at San Antonio’s University Hospital, where he practices, is over 50%.
“When you add RhoGAM [Rho(D) immune globulin, which prevents Rh immunization] into the equation,” Jenkins says, “it becomes a very small likelihood that a woman of childbearing age, given cold stored whole blood, is going to have a problem with antibody development. Meanwhile, if we don’t give it to them, the mortality of that group is overwhelming. So when we talked to our maternal-fetal medicine and obstetrician and pediatrician groups about this, they said, ‘My gosh! Give the transfusion and bring us a live woman! We’ll deal with the other problems down the road.”
That aspect of the program is being written up for journal publication, but in the meantime, other jurisdictions using whole blood might consider giving Rh-positive blood to women, Jenkins says, “because if you’re trying to run an O-negative whole blood program, there just aren’t enough donors.”
A Precious Gift
The benefit to providing whole blood rather than components is that it undergoes less processing: There’s no need to centrifuge it and separate out the parts; there’s no need for separate storage and transport. The bag you donate into is the bag it stays in. And the recipient is only exposed to one donor.
The logistical challenges for Brothers in Arms are 1) having enough blood and 2) keeping it rotated for freshness while minimizing waste.
“We want to keep the whole blood no longer than 35 days,” says Jenkins. “It takes a couple of days after the donation to be certain it’s not going to cause a transfusion-transmissible disease problem. So once the blood bank releases it, it goes right out to the helicopter sites. And when it hits day 14, if it hasn’t been used, then we bring it into one of the trauma centers, because it’s more likely we’ll use it there than they will during the last 14 days of its shelf life.”
If the trauma center hasn’t used the blood by 35 days, it’s returned to STBTC for use in research. “It’s a precious gift these people have provided,” adds Jenkins, “so if it doesn’t get used for its major purpose, it’ll still have some value to the medical community.”
A goal if the program is successful is to expand it to ground ambulances, and in fact a pair of ground services elsewhere in Texas are already providing whole blood. Cypress Creek EMS and the Harris County Emergency Services District #48 Fire Department started delivering packed red blood cells and plasma in the field in 2016, then last year, spurred by the same combat findings, they scaled up to whole blood. (They’re using O-negative blood for women of childbearing age and O-positive for everyone else.) Interestingly, of those who needed RBCs and plasma from CCEMS, only about 44% were trauma patients, while 56% were medical. Other services in the Houston area are expected to sign on as well.
In the San Antonio area, through six weeks of operation, 12 patients have received a total of 41 units of cold stored whole blood at trauma centers under the program with no transfusion-related complications. About a third have died, “down substantially” from historical rates and lower than doctors expected, Jenkins says. A 13th was transfused in the field. No blood has expired or been returned to STBTC.
The prehospital use of cold stored whole blood represents the reversal of a decades-long trend. The Department of Defense moved away from it after Vietnam because of logistical difficulties that included a lot of waste, and the availability of whole blood in trauma centers ended a few years later. Some helicopter services around the country carry red blood cells; fewer carry fresh plasma, and fewer still whole blood. Few ground units carry any blood products.
In Iraq and Afghanistan U.S. medical personnel used warm, fresh whole blood drawn on demand.
“That really was eye-opening for us,” says Jenkins. “We’d lost the knowledge about whole blood and how to use it, when to use it, and its effectiveness, because none of us who were in the combat zone had access to whole blood in our training programs. Our teachers didn’t teach us about it because they were mostly trained in an era when they didn’t have whole blood either. So we were sort of a couple of generations of surgeons removed from access to whole blood. And what we had to go on, literally, was a chapter in a 1988 U.S. revision of the NATO emergency war surgery handbook that described the process by which you could use it.”
Jenkins and colleagues utilized cold blood on a small scale in Afghanistan in 2001: Forward-deployed to secure an airfield, they drew it from their base population and carried it on flights in coolers. They didn’t use much, but it raised the idea of collecting it in advance, rather than as needed, and storing it for future use.
“That changed the logistics of things a bit,” Jenkins says. “But we compared the group that got that whole blood to groups that got just red cells or just red cells and plasma, and that’s where we figured out that the ratio of 1:1:1 transfusions—you have 1:1:1 in your body, and that’s what you bleed when you get injured—made the most sense.”
That also probably translates most easily to the civilian world. If you need large amounts of blood at the ED, you likely needed it before the ED, and EMS can feasibly give it. Transfusions need no longer be a hospital-only intervention.
Still, more trauma patients are transported by ground than air, so to realize the full benefit of a whole-blood program, it should include ground ambulances. That’s in the works in San Antonio, where the plan is to put blood in the hands of EMS supervisors who will respond to MCIs and severe traumas. Hotspotting has already identified key locations where that need should be more likely.
Another possibility is expanding the program beyond San Antonio’s trauma centers to farther-flung parts of the 22 counties under the Southwest Texas Regional Advisory Council’s jurisdiction. In those remote areas are more than a dozen critical-access hospitals with patients who could benefit from transfusion. But none have platelets, and few have timely access to plasma. The goal is to put two units of cold stored whole blood in each of those hospitals as well. That will require more donors but also reduce the likelihood of waste, as blood not used on the helicopters has more potential destinations at its 14-day mark.
Logistical challenges aside, the benefit to patients of cold stored whole blood appears as real in the civilian realm as in the military.
“With the first patient who received cold stored whole blood at University Hospital, that blood was administered by my junior partner and our newest partner who just graduated from our fellowship,” recalls Jenkins. “Both of those individuals, never having been exposed to whole blood, used it to save the patient’s life. They were knocked out by how effective it was, and that was also our experience in the combat zone: You just can’t believe how potent it is at restoring someone’s physiology and getting them to clot.”