Washington – Military scientists want to make sure that injured troops in the battlefield receive the same standard of care as they would receive in a stateside U.S. hospital, especially when it comes to managing hemorrhage.
Hemorrhage is a major problem on the battlefield. Nearly 50% of combat deaths have been due to exsanguinating hemorrhage since the middle of World War II and, of those, about half of those lives could have been saved if timely, appropriate care had been available, according to DoD. In addition, the military reports that post-mortem study of casualties in Operation Iraqi Freedom suggests that up to 18% of all battlefield deaths could be prevented with improved ways to stop and treat severe hemorrhage.
One way researchers are seeking to help patients who have sustained blood loss is by acquiring new technologies and techniques to improve the availability and quality of blood products in theater.
“Often casualties are coming in … to the combat support hospitals who require massive transfusions with blood,” explained Victor MacDonald, PhD, product manager for SME blood products for the Pharmaceutical Systems Project Management Office at the U.S. Army Medical Material Development Activity (USAMMDA). At USAMMDA, project managers oversee the advanced development of products and their path through the regulatory process to obtain FDA approval.
Bringing Blood Platelets to the Battlefield
Platelets are one of the key blood components for normal blood-clotting after an injury or surgery. Supplying platelets to the battlefield is problematic, because, once collected, liquid platelets have a shelf-life of about five days .
“Once the person donates them, they have a very short shelf-life,” explained MacDonald. “So they cannot really be collected in the U.S. and sent overseas. There just isn’t enough time.”
Army Surgeon General Maj. Wertin from the 28th Combat Support Hospital sews up a Soldier’s wound after being hit by shrapnel during an insurgent attack in Mosul, Iraq, May 16.
To that end, military scientists have been interested in cryopreserved platelets (CPP). Originally developed in Boston at the Naval Blood Research Laboratory from 1972 to 2001, research efforts have been under way to build upon that work and get FDA approval for clinical use.
CPP consist of human platelets preserved in dimethyl sulfoxide that are frozen at -80°C and stored at -65°C. These platelets aid in the blood-clotting mechanism for patients who have a deficiency of platelets. The idea behind frozen platelets is that they can be collected and tested in the U.S., frozen and shipped to a location, then thawed as needed.
“The goal is to achieve the standard of therapy in the U.S., or something close to it on the battlefield,” said Rodney Michael, MD, senior product manager for blood products at USAMMDA. “Right now we don’t have that, because we don’t have ready availability of platelets. It is our standard part of treatment of severe trauma in the U.S., and we would like to offer something like or near to that on the battlefield.”
MacDonald explained that frozen platelets would have a longer shelf-life and could be almost immediately available when casualties arrive at a combat support hospital.
“Right now, we are targeting the combat-support hospitals,” he said. “The requirement for this is going to require a freezer that goes to a bit lower temperature then the current freezers out there, but we have identified a new class of freezer that is very light and looks like it is very deployable to hold this material. If you are looking for an ideal platelet product, you would want one that wouldn’t require any refrigeration at all, and you could just leave it on the shelf and pull it down on an as-needed basis like any drug. That does not currently exist.”
CPP is currently in phase I clinical trials in the U.S. However, Michael and MacDonald acknowledge that the path to FDA approval is not clear and that they are working through challenges in moving the product forward.
“Part of the issue is coming to agreement with FDA about what needs to be done to get approval,” said Michael. “What the FDA is most concerned with is safety. That is their paramount consideration. To that end, frozen platelets raise a dilemma for them. They are concerned about them potentially causing blood clots where you don’t want blood clots — in legs or in lungs. They are concerned about that, and we are in ongoing discussions with them to determine exactly what they will require us to do to demonstrate safety.”
MacDonald pointed out that the CPP already is being used safely by the Dutch Military Services and has been fielded in the Balkans and in Afghanistan for use at Dutch medical-treatment facilities. If approved by the FDA, CPP would be produced by military blood banks and managed as a blood product for the battlefield by the Armed Services Blood Program Office.
Blood Products for the Battlefield
In addition to CPP, there are other blood products the military would like to field in theater. Red Blood Cells,
Extended Life (RBCXL) is in phase III clinical trials and was developed by the Walter Reed Army Institute of Research and Hoxworth Blood Center at the University of Cincinnati in partnerships with Hemerus Medical LLC.
This product consists of a new solution that extends the shelf-life of packed red blood cells. It is hoped that the product can improve the quality of the red blood cells in storage, so that cells that have been in storage for four or five weeks would be as good or better than red blood cells currently at two weeks.
“There is a great deal of concern in the surgical community, especially about the quality of red cells in storage,” said Michael. “Currently, red cells are approved to be stored for six weeks. Surgeons think that they do not like red cells that are older than two weeks in storage. So, there has been a big push in theater to get only red cells that are less than two weeks old in theater, which is logistically quite challenging.”
Another product under development is freeze-dried plasma. MacDonald explained that currently plasma is frozen and shipped into theater. Because of breakage of the shipping bags, a significant percentage of the material has to be discarded.
Another challenge with the frozen plasma is that after thawing, it has a refrigerated shelf-life of only about five days. Older plasma must be discarded, MacDonald explained.
“You have to thaw a certain amount of it in anticipation of casualties that may be coming in there and a certain percentage that has to be discarded because of outdating after five days,” said MacDonald. “With freeze-dried plasma, you can ship it into theater and in the refrigerator. It does not have to be thawed. All it has to do is be reconstituted by adding water, and then it is ready to go in less than 5 minutes. From a logistical standpoint, it becomes a more attractive product both in terms of much less loss of product of material and almost instant availability on demand.”
MacDonald added that freeze-dried plasma could be taken further forward into the battlefield, since this product does not have the same refrigeration requirements as frozen plasma.