Blood Shortage on the Battlefield require new blood transfusion, transportation and manufacturing technologies

Rajesh Uppal July 17, 2022 BioScience, Manufacturing Comments Off on Blood Shortage on the Battlefield require new blood transfusion, transportation and manufacturing technologies 262 Views

Blood transfusion is an essential medical practice that is frequently under the threat of limited availability. Each year, 120 million blood donations are realized in the world, of which 50% are accessible to only 16% of the world population. Even in developed countries, shortages are not uncommon (ex. aging population or epidemics limit blood collection). Furthermore, a diversity of donors induces the risk of transmitting diseases, even if the supply chain is carefully controlled.

“The COVID-19 responses have significantly impacted the blood supply leading to a steep drop in donations, causing significant shortages in blood centers across the world,” explains Professor Luc Douay, President and Founder of EryPharm. “Today more than ever we need a reliable supplementary supply of blood cells for transfusion.”

Conducting blood donations and transfusions on the battlefield is far more challenging and this has become a standard training and operating practice for special operations combat medics. Not too long ago, a wounded patient would not receive a blood transfusion until he/she arrived at a medical unit or at minimum until they were loaded onto a medevac helicopter with highly qualified medics. Medics would carry IV bags containing Hextend and Tranexamic acid (TXA), used for fluid resuscitation and blood loss mitigation for patients in hemorrhagic shock (i.e. for someone who had lost a lot of blood). Even with high-speed life-saving capabilities, there were operators still dying from wounds that they may have otherwise survived if they had received supplemental blood sooner. According to the Army Blood Program, it is estimated that 90 percent of preventable deaths in combat are due to blood loss.

It is no secret that the fundamental way to save the life of a person who has lost a lot of blood is to first stop the bleeding and then give them more blood. A fresh, whole blood transfusion is the holy grail for treating patients who have lost life-threatening amounts of blood (also known as massive hemorrhage), but the logistical challenges of collecting and transfusing fresh blood in combat scenarios are daunting. If the wrong blood type is given to a patient, it will trigger an adverse immune reaction that can result in death. Even with universal-donor blood (type O), a high titer level — a measure of antibody proteins — in the blood can potentially trigger an immune response that is dangerous for a critically wounded patient.

Bloodborne pathogens are another concern, as is the time it takes to collect blood. Hemorrhagic casualties have precious little time to spare; even if a donor is already next to the casualty, it can take more than 15 minutes to collect the blood and perform the transfusion.

In any special operations unit, it is critical for the medic to document the blood type of each team member. Of course, in cool guy pictures and movies, you often see guys’ blood types velcroed to their helmets, kits, and shoulder patches. This isn’t just to look “cool”. It is a life-saving technique used by medics on the ground, medevac aircrews, and surgeons.

A good medic will have conducted blood type compatibility testing and documented the results for all members on his team prior to deployment. Blood type compatibility testing can be complicated. The donor’s and the recipient’s blood should always be tested before donating/transfusing takes place. It’s not ideal trying to conduct this kind of testing in a combat zone, while a guy is bleeding out.

A special operations medic in the field cannot carry blood bags for each individual guy, some will carry a few bags of whole blood, but this blood will run out quickly with a severely wounded trauma patient. Medics carry ready-to-go donation/transfusion kits. If an operator sustains a critical wound, the medic can immediately start filling a blood bag from another team member who has compatible blood. Once the blood bag is filled, the medic can start transfusing this blood to the patient, while another donor bag is being filled.

Whole blood transfusions are basically the drawing of blood directly from a donor and then transfusing it right into the recipient. The transfusion of warm, whole blood serves two factors: it has the ability to help a patient clot and is able to help warm them at the same time. One of the biggest killers outside of the wound itself is hypothermia.

“Especially across a major battlefield where you may be all that is standing between whether a Soldier lives or dies.” It takes about 10-12 minutes to draw the blood from the donor. The medic can then hook up the bag directly to the IV of the patient and start the transfusion. “So in less than 15 minutes the casualty can be receiving the fresh whole blood,” said Allen. “I can collect and transfuse the blood right in the back of a Bradley if necessary.”

Although fresh whole blood is the best replacement, Rangers primarily use whole blood that has been stored cold and carried by the medics on missions. This cold-stored whole blood can be rapidly warmed by a buddy lite or similar device and transfused into a patient with greater speed than fresh whole blood can be collected.

The resuscitative power of cold-stored whole blood, while somewhat less than that of fresh whole blood, is much greater than alternative techniques, such as using reconstituted blood. Reconstituted blood consists of taking individually packaged components of human blood, such as packed red blood cells (PRBCs), freeze-dried or fresh-frozen plasma (FDP and FFP), and platelets, and administering them in a 1:1:1 ratio that mimics whole blood. Plasma is the protein-rich liquid in which the rest of the blood’s components are suspended. Platelets are small cell fragments that help form clots during bleeding. Red blood cells carry oxygen out to the body’s tissues, and bring back carbon dioxide to be exhaled. Both plasma and platelets play a role in blood’s clotting ability.

The storage and acquisition of these components present their own logistical difficulties, such as the short shelf-life of platelets. Most importantly, reconstituted blood does not return the same level of oxygen-carrying capacity and clot-formation functions to a patient as whole blood. The data support the intuitive conclusion that when whole blood is lost, the best thing to replace it with is more whole blood.

The Ranger Regiment has designed the ROLO Program to mitigate the potential for adverse reactions of battlefield whole blood transfusions. To that end, Group O, low-titer Rangers who are free of bloodborne diseases are identified through a series of highly reliable blood tests, and these Rangers (often simply called ROLOs) are placed on a roster of available donors for their platoons.

It is imperative that critically wounded patients are moved to a hospital for surgery as soon as possible because these resuscitative techniques can only buy them a limited amount of time. If a casualty is in bad enough shape to require a battlefield blood transfusion, they likely need surgery. The hope is that blood transfusions will keep critical casualties alive long enough to get them to the surgery or surgeries that will ultimately save their lives.

Technology to generate red blood cells from stem cells

The Uniformed Services University of the Health Sciences’ 4D Bio3 On-Demand Blood Program, or 4D Bio3 Blood, is developing highly efficient protocols and technology to generate red blood cells from stem cells. A key part of this technology is large-scale cell expansion at low cost, producing sufficient red blood cells for treatment in trauma care. This technology is also being adapted to create neutrophils, ultimately allowing for whole blood transfusion using these methods in the future.

Currently, blood used for trauma care is obtained from human donors and is reliant on donor health, a robust network of blood donation, capacity for long-term storage, and extensive testing. Cell culture systems can be relatively small and easy to transport, making it possible to fabricate blood in locations where it is needed most. The potential of manufacturing human red blood cells safe for human transfusion on-site, even in an austere location, reduces the need for extensive donor networks, donor blood screening concerns and streamlines logistics related to processing, long-term storage and transport of blood.

“Ensuring the health and readiness of our warfighters is becoming increasingly challenging with our changing global threats that typically require our service members to operate in austere environments and under very extreme conditions. Adaptation of novel biotechnology for use near the point-of-need can provide the solutions necessary to make certain that our warfighters are prepared and also provided the best healthcare, regardless of their location,” stated Dr. Vincent Ho, director of 4D Bio3 and chair of Radiology at USU.

Biotech EryPharm Announces a Revolutionary Technological Breakthrough in the Large- Scale Manufacturing of Red Blood Cells

EryPharm, startup created in 2016, has achieved a revolutionary technological breakthrough to mass-produce cultured red blood cells to develop new sourcing for blood transfusion. Supporting and complementing regular blood donation, this medical product will improve the quality of life of multi-transfused patients who suffer from hereditary or acquired diseases of the red blood cells in particular.

After four years of Research and Development, EryPharm is now entering a pilot production phase and scale-up of Cultured Red Blood Cells (cRBC) using Hematopoietic Stem Cells (HSC). The new drug will complement the conventional transfusion thanks to its multiple benefits:

Because the population of cultured red blood cells is homogeneously young, their lifespan is expected to be significantly increased. This improved efficacy would allow the reduction of transfusion needs and improves the quality of life for patients. Generated from native adult stem cells, they do not necessitate any genetic modification nor pose any ethical problem.

HSC have been widely used worldwide for decades, and the techniques to collect, prepare, and freeze them are perfectly mastered.
HSC can be stored in the long-term, ensuring sustained visibility of red blood cells when needed.
HSC have a great capacity for proliferation and differentiation, making them ideal for producing cRBC for transfusion purposes. “A HSC single donation will produce the equivalent of a hundred blood donations! This is a milestone in the history of blood transfusion,” mentions Professor Luc Douay.
Transfusion of cultured red blood cells will contribute to decreasing the risks of immunization, infection, and iron overload, resulting in significant medical cost savings.

cRBC will benefit especially patients treated for chronic anemias or with rare blood groups. Hereditary Hemoglobinopathies affect over 25 million people, for whom EryPharm may have a dramatic impact as their transfusions account for 30% of the RBC units used for treating chronic anemia. EryPharm will allow these patients to be transfused in the best conditions of compatibility. With today’s breakthrough, EryPharm is now completing its second funding round to jumpstart industrial production.

“We are more than thrilled to pave the way to prevent blood shortage and propose to patients in the near future an effective and safe technology,” indicates Professor Luc Douay. “With EryPharm, we will be able to deliver an improved transfusion treatment to patients in recurrent need, whether they suffer from acquired or inherited anemia. More than a new drug, EryPharm paves the way to a new paradigm for transfusion medicine,” he concludes.

Army Testing Drones for Medical Logistics reported in Jan 2022

US Army is testing drones and autonomous technology that could deliver life-saving medical supplies to the battlefield. During test flights held at Fort Pickett, Virginia, in August, Pittsburgh-based Near Earth Autonomy integrated its autonomous flight systems onto an L3Harris-built FVR-90 hybrid vertical take-off and landing unmanned aerial vehicle. The flights demonstrated how the drone could be used to send supplies back and forth across hundreds of miles, the companies said.

During the demonstrations, the FVR-90 and Near Earth’s systems underwent multiple scenarios to test how they could deliver supplies. Near Earth’s sensors were able to find unobstructed areas for the drone to land, according to a news release. When landing wasn’t possible, the supply pods were dropped from a low altitude or released higher up via parachutes, it said.

The autonomy systems built by Near Earth allow the unmanned aircraft to fly to designated coordinates and scan the environment using onboard sensors to determine the optimal supply delivery location, said Sanjiv Singh, the company’s CEO.

Along with the ability for vertical launch and recovery, the FVR-90 can carry a payload of up to 20 pounds inside delivery pods, said Peter Blocker, director of tactical UAS at L3Harris. This includes refrigerated pods of blood or other lightweight medical supplies. The platform is able to fly for up to 16 hours, according to L3Harris. Additionally, the drone can travel approximately 50 miles, or even farther with a larger antenna, Blocker said. “That’s the part that’s just amazing — being able to fly this out, say 40 or 50 miles away from wherever your supply is, and dropping it,” he said. Researchers hope the technology will also help reduce the amount of blood wasted during operations.

“Blood is really a commodity,” Fisher said. While medics usually carry blood with them for transfusions, it’s difficult to return unused blood to banks before they go bad, he added. With a long-endurance drone, medics could send blood either back to the blood bank or even to another medic who needs it, Singh noted.