Pathogen Reduced Cryoprecipitate and Fibrinogen Concentrate Have Delayed Resuscitation of Simulated Dilutional Coagulopathy in a Microfluidic Model of Bleeding When Compared to Cryoprecipitate

Impaired fibrinogen function, one component of trauma-associated coagulopathy, is highly associated with increased mortality in patients with severe traumatic bleeding. Fibrinogen replacement is crucial for improving outcomes in bleeding patients. The two most common clinically-used hemostatic adjuncts for fibrinogen supplementation are fibrinogen concentrates (FibCon) and cryoprecipitate (Cryo), yet which of these products provides better hemostatic resuscitation remains controversial. Where FibCon is predominantly a source of fibrinogen, Cryo contains additional factors which may enhance hemostatic efficacy, such as FVIII and FXIII (inherent to clot strength and fibrin crosslinking) and von Willebrand factor (VWF, important for platelet adhesion and aggregation). Cryo poses more logistical challenges than FibCon, as Cryo is a frozen product that requires thawing (20 minutes) prior to use, and has a shelf life of 4-6 hours post thaw. FibCon is lyophilized, and can be reconstituted and used within 10 minutes, but with a cost roughly 3 times that of Cryo, use of FibCon can be cost-prohibitive. Ultimately, in the setting of hemostatic resuscitation, every minute matters and each minute delay in blood product transfusion is associated with a 5% increase in mortality. Moreover, Cryo is associated with an increased risk of transfusion transmitted infection (TTI).Thus, there is a need for an immediately available and safe fibrinogen source for use in hemostatic resuscitation. Pathogen reduction (PR) of blood products renders any nucleic acid-containing source replication incompetent via crosslinking using psoralens and ultraviolet light. PR was recently adapted for use with cryoprecipitate, yielding a novel hemostatic adjunct - pathogen reduced cryoprecipitated fibrinogen complex, or PR-Cryo FC. We have previously shown PR-Cryo FC stored out to 10 days performs similarly to Cryo and FibCon in current standard assays used to assess hemostatic function. However, as primary hemostasis is dictated by physiologically relevant flow conditions, we wanted to determine if PR of cryoprecipitate altered its hemostatic function during resuscitation of dilutional coagulopathy using a microfluidic model of hemorrhage. Healthy human whole blood (WB), Cryo, FibCon, and PR-Cryo FC were stained with fluorescent antibodies specific for VWF, CD41, fibrinogen, and FXIII. Stained WB was diluted 3:7 in 0.9% NaCl to induce dilutional coagulopathy (dWB). dWB was resuscitated 1:5 with stained adjuncts (Cryo:dWB, FibCon:dWB, or PR-Cryo FC:dWB) and perfused at three different shear rates (150, 500, 3500 1/s) through a microfluidic model of hemorrhage (a lumen that "bleeds" through an injury site into a collagen/tissue factor-coated extravascular space). Occlusion of the injury site was defined as the point at which clot formation sealed the injury site for > 3 minutes. The time from initial perfusion to occlusion was defined as the bleeding time (BT, seconds). If no seal was formed, the assay was stopped at 20 minutes, and the assay given a BT of 1200 seconds. Real-time phase and fluorescent images of the injury site were acquired. Data was extracted from real-time phase and fluorescent images using MATLAB. Both FibCon:dWB and PR-Cryo FC:dWB had significantly increased BT compared to Cryo:dWB at low shear (150 1/s). PR-Cryo FC:dWB had significantly increased BT compared to Cryo:dWB at medium shear (500 1/s), and at high shear (3500 1/s) there were no significant differences in BT between hemostatic adjuncts. However, kinetic analysis at high shear revealed there was a significant delay in clot formation and accumulation in the injury site, such that by 5 minutes, Cryo:dWB had filled 75% of the injury site and FibCon:dWB and PR-Cryo FC:dWB had only filled 50% of the injury site. Real-time fluorescent image analysis showed that both FibCon:dWB and PR-Cryo FC:dWB had reduced VWF deposition at the injury site compared to Cryo:dWB, and this led to a delays in platelet recruitment. FibCon has less VWF than Cryo, which would explain the delayed VWF deposition and platelet recruitment. In contrast, PR-Cryo FC and Cryo have similar amounts of VWF, suggesting that VWF from PR-Cryo FC has limited binding to the collagen-coated injury site, and as PR-Cryo FC:dWB phenocopies FibCon:dWB during clot formation at high shear, this suggests that pathogen reduction of Cryo may impair early VWF mediated capture of platelets at high shear. Disclosures Spinella: Secure Transfusion Services: Current Employment, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company; Cerus Corporation: Consultancy, Research Funding.

Damage control in the emergency department, a bridge to life

Patients with hemodynamic instability have a sustained systolic blood pressure less or equal to 90 mmHg, a heart rate greater or equal to 120 beats per minute and an acute compromise of the ventilation/oxygenation ratio and/or an altered state of consciousness upon admission. These patients have higher mortality rates due to massive hemorrhage, airway injury and/or impaired ventilation. Damage control resuscitation is a systematic approach that aims to limit physiologic deterioration through a group of strategies that address the physiologic debt of trauma. This article aims to describe the experience earned by the Trauma and Emergency Surgery Group (CTE) of Cali, Colombia in the management of the severely injured trauma patient in the emergency department following the basic principles of damage control surgery. Since bleeding is the main cause of death, the management of the severely injured trauma patient in the emergency department requires a multidisciplinary team, which should perform damage control maneuvers aimed at rapidly control bleeding, hemostatic resuscitation and/or prompt transfer to the operating room, if required.

Exsanguinating hemorrhage from coccygeal fracture dislocation: First report of a life-threatening injury

Background: Penetrating injuries to sacrum are rare; only a few reports have been published in literature. We hereby report the first case of low velocity penetrating trauma leading to coccygeal fracture dislocation and exsanguination, without any major abdominal/vascular injury. Case Report: The patient underwent wound packing bedside and hemostatic resuscitation. Wound packing was successful in achieving hemostasis. He stabilized after 1.5 L of fluids, massive hemorrhage protocol institution (12-unit blood components), and vasopressor support. The presentation is unique and not reported in literature published so far. Conclusion: This report is a pertinent example of lifesaving potential of effective wound packing, which is often under-utilized. Possibility of associated neurological injury and residual foreign bodies is there in such cases. They should be duly assessed after stabilizing life-threatening injuries.

Lessons Learned From the Battlefield and Applicability to Veterinary Medicine – Part 2: Transfusion Advances

Since the inception of recent conflicts in Afghanistan and Iraq, transfusion practices in human military medicine have advanced considerably. Today, US military physicians recognize the need to replace the functionality of lost blood in traumatic hemorrhagic shock and whole blood is now the trauma resuscitation product of choice on the battlefield. Building on wartime experiences, military medicine is now one of the country's strongest advocates for the principle of hemostatic resuscitation using whole blood or balanced blood components as the primary means of resuscitation as early as possibly following severe trauma. Based on strong evidence to support this practice in human combat casualties and in civilian trauma care, military veterinarians strive to practice similar hemostatic resuscitation for injured Military Working Dogs. To this end, canine whole blood has become increasingly available in forward environments, and non-traditional storage options for canine blood and blood components are being explored for use in canine trauma. Blood products with improved shelf-life and ease of use are not only useful for military applications, but may also enable civilian general and specialty practices to more easily incorporate hemostatic resuscitation approaches to canine trauma care.