Trauma patients have reduced ex vivo flow-dependent platelet hemostatic capacity in a microfluidic model of vessel injury.

Trauma is the leading cause of death in individuals up to 45 years of age. Alterations in platelet function are a critical component of trauma-induced coagulopathy (TIC), yet these changes and the potential resulting dysfunction is incompletely understood. The lack of clinical assays available to explore platelet function in this patient population has hindered detailed understanding of the role of platelets in TIC. The objective of this study was to assess trauma patient ex vivo flow-dependent platelet hemostatic capacity in a microfluidic model. We hypothesized that trauma patients would have flow-regime dependent alterations in platelet function. Blood was collected from trauma patients with level I activations (N = 34) within 60 min of hospital arrival, as well as healthy volunteer controls (N = 10). Samples were perfused through a microfluidic model of injury at venous and arterial shear rates, and a subset of experiments were performed after incubation with fluorescent anti-CD41 to quantify platelets. Complete blood counts were performed as well as plasma-based assays to quantify coagulation times, fibrinogen, and von Willebrand factor (VWF). Exploratory correlation analyses were employed to identify relationships with microfluidic hemostatic parameters. Trauma patients had increased microfluidic bleeding times compared to healthy controls. While trauma patient samples were able to deposit a substantial amount of clot in the model injury site, the platelet contribution to microfluidic hemostasis was attenuated. Trauma patients had largely normal hematology and plasma-based coagulation times, yet had elevated D-Dimer and VWF. Venous microfluidic bleeding time negatively correlated with VWF, D-Dimer, and mean platelet volume (MPV), while arterial microfluidic bleeding time positively correlated with oxygenation. Arterial clot growth rate negatively correlated with red cell count, and positively with mean corpuscular volume (MCV). We observed changes in clot composition in trauma patient samples reflected by significantly diminished platelet contribution, which resulted in reduced hemostatic function in a microfluidic model of vessel injury. We observed a reduction in platelet clot contribution under both venous and arterial flow ex vivo in trauma patient samples. While our population was heterogenous and had relatively mild injury severity, microfluidic hemostatic parameters correlated with different patient-specific data depending on the flow setting, indicating potentially differential mechanistic pathways contributing to platelet hemostatic capacity in the context of TIC. These data were generated with the goal of identifying key features of platelet dysfunction in bleeding trauma patients under conditions of flow and to determine if these features correlate with clinically available metrics, thus providing preliminary surrogate markers of physiological platelet dysfunction to be further studied across larger cohorts. Future studies will continue to explore those relationships and further define mechanisms of TIC and their relationship with patient outcomes.

The rebirth of the cool: a narrative review of the clinical outcomes of cold stored low titer group O whole blood recipients compared to conventional component recipients in trauma.

There has been renewed interest in the use of low titer group O whole blood (LTOWB) for the resuscitation of civilian casualties. LTOWB offers several advantages over conventional components such as providing balanced resuscitation in one bag that contains less additive/preservative solution than an equivalent volume of conventional components, is easier and faster to transfuse than multiple components, avoids blood product ratio confusion, contains cold stored platelets, and reduces donor exposures. The resurgence in its use in the resuscitation of civilian trauma patients has led to the publication of an increasing number of studies on its use, primarily amongst adult recipients but also in pediatric patients. These studies have indicated that hemolysis does not occur amongst adult and pediatric non-group O recipients of a modest quantity of LTOWB. The published studies to date on mortality have shown conflicting results with some demonstrating a reduction following LTOWB transfusion while most others have not shown a reduction; there have not been any studies to date that have found significantly increased overall mortality amongst LTOWB recipients. Similarly, when other clinical outcomes, such as venous thromboembolism, sepsis, hospital or intensive care unit lengths of stay are evaluated, LTOWB recipients have not demonstrated worse outcomes compared to conventional component recipients. While definitive proof of the trends in these morbidity and mortality outcomes awaits confirmation in randomized controlled trials, the evidence to date indicates the safety of transfusing LTOWB to injured civilians.

Practical Considerations for a Military Whole Blood Program.

INTRODUCTION: Prehospital care in the combat environment has always been of great importance to the U.S. military, and trauma resuscitation has remained a cornerstone. More evidence continues to demonstrate the advantages of intervention with early transfusion of blood products at the point of injury. The military has recognized these benefits; as such, the Department of Defense Joint Trauma System and the Committee on Tactical Combat Casualty Care have developed new advanced resuscitation guidelines, which now encourage the use of whole blood (WB) in the prehospital setting. MATERIALS AND METHODS: This general review of peer-reviewed journal articles was performed through an extensive electronic search from the databases of PubMed Central (MEDLINE) and the Cochrane Library. RESULTS: Based on this literature search, the current evidence suggests that transfusion with WB is safe and efficacious. Additionally, soldier function is preserved after donating fresh WB in the field. Currently, the collection and implementation of WB is accomplished through several different protocol-driven techniques. CONCLUSION: WB has become the favored transfusion product as it provides all of the components of blood in a convenient package that is easy to store and transport. Specifically, group O WB containing low titers of anti-A and -B antibodies has become the transfusion product of choice, offering the ability to universally fluid resuscitate patients despite not knowing their blood group. This new ability to obtain low titer group O WB has transformed the approach to the management of hemorrhagic shock in the prehospital combat environment.