Coagulation and Blood Research Program

MISSION

Our objective is to decrease battlefield mortality due to hemorrhage by providing diagnostics and therapeutics to treat the Coagulopathy of Trauma (COT) with safe and effective blood products delivered far-forward.

We are addressing the following capability gaps:

1) COT is present in 25% of trauma patients and is associated with increased mortality and blood use. These patients are at high risk of death and represent the largest proportion of preventable fatalities on the battlefield. The diagnostic criteria for COT are imprecise and risk stratification of patients is unavailable. Targeted therapeutics are unavailable, and overall, there is no standard of care for COT.

2) Blood product availability far-forward, closest to point of injury, remains a challenge. Platelets are critical for hemorrhage control and are difficult to supply due to short lifespan (5 days) and current storage (22°C on an agitator). Available platelet products carry a risk of bacterial contamination and may not be optimal for treatment of hemorrhage/COT.

COAGULOPATHY OF TRAUMA STUDIES

Description:

Approximately 25% of trauma patients manifest signs of coagulation function abnormalities at the time of initial presentation to a trauma center, prior to receiving significant intravenous fluid therapy that would cause a dilutional coagulopathy.

The cause of this early coagulopathy of trauma may involve activation of Protein C and fibrinolysis, but its underlying mechanisms are not well-described.

Coagulopathy of trauma is associated with increased blood product use, as well as increased morbidity and mortality.

A better understanding of this complex pathophysiology is needed to improve trauma resuscitation.

Issue Addressed:

Transfusion strategies for combat casualties have evolved recently to incorporate the empirical use of red cells, platelets, plasma, and cryoprecipitate in order to control hemorrhage and reverse the coagulopathy of trauma.

Since the fundamental pathophysiology of this coagulopathy is unknown, it is also unknown whether all blood components currently used are necessary or even beneficial.

It is possible that certain components exacerbate the development of this coagulopathy. For example, red cells may provoke damaging inflammatory responses, and the addition of clotting factors that support thrombin generation may cause excess Protein C activation which ultimately results in pathological depletion of key factors and induction of inappropriate fibrinolysis.

The role of platelets in mediating or correcting the coagulopathy of trauma is almost completely unknown. Similarly, the role of cell-derived microparticles in this process is unclear.

A critical aspect of research in this area will be the identification of novel or improved tests of coagulation function since the coagulopathy of trauma has been defined using assays such as the prothrombin time, which are inadequate for capturing the complexity of the interactions of platelets, coagulation factors, the endothelium, and the immune system.

Expected Results:

This program of research will generate a better understanding of the mechanisms underlying the coagulopathy of trauma and will guide improvements in the use of currently available blood products and pharmaceuticals.

Ultimately, this program will result in the development of improved diagnostics and targeted therapies that optimize trauma care and reduce the ineffective (and perhaps harmful) use of scarce blood products that could find better use in other clinical settings.

PLATELET STORAGE STUDIES

Description:

New platelet storage technologies that preserve hemostatic effectiveness while extending product shelf life are critical to improving platelet availability in both military and civilian settings.

Issue Addressed:

Providing blood product availability far-forward, closest to the point of injury, remains a challenge. Platelets are critical for hemorrhage control and are difficult to supply due to short lifespan (5 days) and current storage practices (22°C on an agitator).

Currently available platelet products carry a risk of bacterial contamination and may not be optimal for hemorrhage control and treatment of coagulopathy of trauma. Novel approaches to platelet storage are needed to support the care of the warfighter.

Expected Results:

This program will transition an improved platelet storage technology to advanced development, with the goal of FDA approval. This program will support development of engineered blood products for the treatment of hemorrhage and coagulopathy of trauma with far-forward delivery.

RESEARCH COLLABORATIONS

The USAISR Coagulation & Blood Research Program maintains extensive collaborations with number of partners in government, academe and industry. In addition to collaborations with USAISR colleagues, we work closely with the US Special Operations Command and combat support medical units to gain in-depth knowledge of battlefield conditions and the unique needs of our deployed forces.

We also maintain international partnerships with researchers in the French, Norwegian and UK militaries.

Our academic collaborators include teams of investigators at Harvard, Mayo Clinic, UCSF, UT Health Science Center - Houston, UT Health Science Center – San Antonio, UT San Antonio, UT Southwestern and U Vermont. Finally,we support advanced product development with industry partners sponsored by the US Army Medical Materiel Development Activity (USAMMDA).