Andrew P. Cap

Ten-year analysis of transfusion in Operation Iraqi Freedom and Operation Enduring Freedom: increased plasma and platelet use correlates with improved survival.

BACKGROUND The Joint Theater Trauma Registry database, begun early in Operation Iraqi Freedom and Operation Enduring Freedom, created a comprehensive repository of information that facilitated research efforts and produced rapid changes in clinical care. New clinical practice guidelines were adopted throughout the last decade. The damage-control resuscitation clinical practice guideline sought to provide high-quality blood products in support of tissue perfusion and hemostasis. The goal was to reduce death from hemorrhagic shock in patients with severe traumatic bleeding. This 10-year review of the Joint Theater Trauma Registry database reports the military’s experience with resuscitation and coagulopathy, evaluates the effect of increased plasma and platelet (PLT)–to–red blood cell ratios, and analyzes other recent changes in practice. METHODS Records of US active duty service members at least 18 years of age who were admitted to a military hospital from March 2003 to February 2012 were entered into a database. Those who received at least one blood product (n = 3,632) were included in the analysis. Data were analyzed with respect to interactions within and between categories (demographics, admission characteristics, hospital course, and outcome). Transfusions were analyzed with respect to time, survival, and effect of increasing transfusion ratios. RESULTS Coagulopathy was prevalent upon presentation (33% with international normalized ratio ≥ 1.5), correlated with increased mortality (fivefold higher), and was associated with the need for massive transfusion. High transfusion ratios of fresh frozen plasma and PLT to red blood cells were correlated with higher survival but not decreased blood requirement. Survival was most correlated with PLT ratio, but high fresh frozen plasma ratio had an additive effect (PLT odds ratio, 0.22). CONCLUSION This 10-year evaluation supports earlier studies reporting the benefits of damage-control resuscitation strategies in military casualties requiring massive transfusion. The current analysis suggests that defects in PLT function may contribute to coagulopathy of trauma. LEVEL OF EVIDENCE Epidemiologic study, level IV.

Massive transfusion and nonsurgical hemostatic agents.

Background:Hemorrhage in trauma is a significant challenge, accounting for 30% to 40% of all fatalities, second only to central nervous system injury as a cause of death. However, hemorrhagic death is the leading preventable cause of mortality in combat casualties and typically occurs within 6 to 24 hrs of injury. In cases of severe hemorrhage, massive transfusion may be required to replace more than the entire blood volume. Early prediction of massive transfusion requirements, using clinical and laboratory parameters, combined with aggressive management of hemorrhage by surgical and nonsurgical means, has significant potential to reduce early mortality. Discussion:Although the classification of massive transfusion varies, the most frequently used definition is ten or more units of blood in 24 hrs. Transfusion of red blood cells is intended to restore blood volume, tissue perfusion, and oxygen-carrying capacity; platelets, plasma, and cryoprecipitate are intended to facilitate hemostasis through prevention or treatment of coagulopathy. Massive transfusion is uncommon in civilian trauma, occurring in only 1% to 3% of trauma admissions. As a result of a higher proportion of penetrating injury in combat casualties, it has occurred in approximately 8% of Operation Iraqi Freedom admissions and in as many as 16% during the Vietnam conflict. Despite its potential to reduce early mortality, massive transfusion is not without risk. It requires extensive blood-banking resources and is associated with high mortality. Summary:This review describes the clinical problems associated with massive transfusion and surveys the nonsurgical management of hemorrhage, including transfusion of blood products, use of hemostatic bandages/agents, and treatment with hemostatic medications.

Tranexamic Acid for Trauma Patients: A Critical Review of the Literature

BACKGROUND Tranexamic acid (TXA) is an antifibrinolytic that inhibits both plasminogen activation and plasmin activity, thus preventing clot break-down rather than promoting new clot formation. TXA has been used around the world to safely control bleeding since the 1960s. A large randomized trial recently conducted in >20,000 trauma patients adds to the large body of data documenting the usefulness of TXA in promoting hemostasis. METHODS We reviewed the literature describing use of TXA in a variety of settings including trauma. RESULTS TXA has been safely used across a wide range of clinical settings to control hemorrhage. The results of a large, randomized, placebo-controlled trial support the use of TXA to treat bleeding trauma patients. CONCLUSIONS This inexpensive and safe drug should be incorporated into trauma clinical practice guidelines and treatment protocols. Further research on possible alternate mechanisms of action and dosing regimens for TXA should be undertaken. Concurrent to these endeavors, TXA should be adopted for use in bleeding trauma patients because it is the only drug with prospective clinical evidence to support this application.

Comparison of Platelet Transfusion as Fresh Whole Blood Versus Apheresis Platelets for Massively Transfused Combat Trauma patients

BACKGROUND: At major combat hospitals, the military is able to provide blood products to include apheresis platelets (aPLT), but also has extensive experience using fresh whole blood (FWB). In massively transfused trauma patients, we compared outcomes of patients receiving FWB to those receiving aPLT.

The Evolving Role of Lyophilized Plasma in Remote Damage Control Resuscitation in the French Armed Forces Health Service

Freeze‐dried plasma was developed by the US Army for the resuscitation of combat casualties during World War II. The French Military Blood Institute began producing French lyophilized plasma (FLYP) in 1949, in accordance with French blood product guidelines. Since 2010, a photochemical pathogen inactivation process has been implemented to reduce the remaining transfusion‐related infectious risk. All quality controls for this procedure verify that the hemostatic properties of FLYP are conserved. FLYP is compatible with all blood types, can be stored at room temperature for 2 years, and its reconstitution requires less than 6 minutes. As a result, FLYP allows quick delivery of all the coagulation proteins and the application of a 1:1 ratio of FLYP and red blood cells in the context of a massive transfusion. Hemovigilance data collected in France since 1994 have included FLYP. Results indicate no reporting of infection related to the use of FLYP. Clinical monitoring with a focus on hemostasis was implemented in 2002 and expanded in 2010. The data, obtained from overseas operations, confirmed the indications, the safety and the clinical efficacy of FLYP. Further research is needed to determine specific indications for FLYP in the therapeutic management of civilian patients with severe hemorrhage.

Constant Challenges and Evolution of US Military Transfusion Medicine and Blood Operations in Combat

BACKGROUND: Blood operations are constrained by many limitations in combat settings. As a result there are many challenges that require innovative solutions.

Timing and location of blood product transfusion and outcomes in massively transfused combat casualties.

BACKGROUND Hemostatic resuscitation using blood components in a 1:1:1 ratio of platelets:fresh frozen plasma:red blood cells (RBCs) is based on analyses of massive transfusion (MT, ≥10 RBC units in 24 hours). These 24-hour analyses are weakened by survival bias and do not describe the timing and location of transfusions. Mortality outcomes associated with early (first 6 hours) resuscitation incorporating platelets, for combat casualties requiring MT, have not been reported. METHODS We analyzed records for 8,618 casualties treated at the United States military hospital in Baghdad, Iraq, between January 2004 and December 2006. Patients (n = 414) requiring MT, not receiving fresh whole blood, and surviving at least 1 hour (reducing survival bias) were divided into 6-hour apheresis platelet (aPLT) transfusion ratio groups: LOW (aPLT:RBC, ⩽0.1, n = 344) and HIGH (aPLT:RBC, >0.1, n = 70). Baseline characteristics of groups were compared. Factors influencing survival on univariate analysis were included in Cox proportional hazards models of 24-hour and 30-day survival. RESULTS Patients received aPLT in the emergency department (4%), operating room (45%), intensive care unit (51%). The HIGH group presented with higher (p < 0.05) admission International Normalized Ratio (1.6 vs. 1.4), base deficit (8 vs. 7), and temperature (36.7 vs. 36.4). Overall mortality was 27%. At 24 hours, the HIGH group showed lower mortality (10.0% vs. 22.1%, p = 0.02). Absolute differences in 30-day mortality were not significant (HIGH, 18.6%; LOW, 28.8%, p = 0.08). On adjusted analysis, the HIGH group was independently associated with increased survival: LOW group mortality hazard ratios were 4.1 at 24 hours and 2.3 at 30 days compared with HIGH group (p = 0.03 for both). Increasing 6-hour FFP:RBC ratio was also independently associated with increased survival. CONCLUSION Early (first 6 hours) hemostatic resuscitation incorporating platelets and plasma is associated with improved 24-hour and 30-day survival in combat casualties requiring MT. LEVEL OF EVIDENCE Therapeutic study, level III.

Mechanisms of early trauma-induced coagulopathy: The clot thickens or not?

Abstract Traumatic-induced coagulopathy (TIC) is a hemostatic disorder that is associated with significant bleeding, transfusion requirements, morbidity and mortality. A disorder similar or analogous to TIC was reported around 70 years ago in patients with shock, hemorrhage, burns, cardiac arrest or undergoing major surgery, and the condition was referred to as a “severe bleeding tendency,” “defibrination syndrome,” “consumptive disorder,” and later by surgeons treating US Vietnam combat casualties as a “diffuse oozing coagulopathy.” In 1982, Moore’s group termed it the “bloody vicious cycle,” others “the lethal triad,” and in 2003 Brohi and colleagues introduced “acute traumatic coagulopathy” (ATC). Since that time, early TIC has been cloaked in many names and acronyms, including a “fibrinolytic form of disseminated intravascular coagulopathy (DIC).” A global consensus on naming is urgently required to avoid confusion. In our view, TIC is a dynamic entity that evolves over time and no single hypothesis adequately explains the different manifestations of the coagulopathy. However, early TIC is not DIC because an increased thrombin-generating potential in vitro does not imply a clinically relevant thrombotic state in vivo as early TIC is characterized by excessive bleeding, not thrombosis. DIC with its diffuse anatomopathologic fibrin deposition appears to be a latter phase progression of TIC associated with unchecked inflammation and multiple organ dysfunction.

Emergency whole-blood use in the field: a simplified protocol for collection and transfusion.

ABSTRACT Military experience and recent in vitro laboratory data provide a biological rationale for whole-blood use in the treatment of exsanguinating hemorrhage and have renewed interest in the reintroduction of fresh whole blood and cold-stored whole blood to patient care in austere environments. There is scant evidence to support, in a field environment, that a whole blood–based resuscitation strategy is superior to a crystalloid/colloid approach even when augmented by a limited number of red blood cell (RBC) and plasma units. Recent retrospective evidence suggests that, in this setting, resuscitation with a full compliment of RBCs, plasma, and platelets may offer an advantage, especially under conditions where evacuation is delayed. No current evacuation system, military or civilian, is capable of providing RBC, plasma, and platelet units in a prehospital environment, especially in austere settings. As a result, for the vast minority of casualties, in austere settings, with life-threatening hemorrhage, it is appropriate to consider a whole blood–based resuscitation approach to provide a balanced response to altered hemostasis and oxygen debt, with the goal of reducing the risk of death from hemorrhagic shock. To optimize the successful use of fresh whole blood/cold-stored whole blood in combat field environments, proper planning and frequent training to maximize efficiency and safety will be required. Combat medics will need proper protocol-based guidance and education if whole-blood collection and transfusion are to be successfully and safely performed in austere environments. In this article, we present the Norwegian Naval Special Operation Commando unit–specific remote damage control resuscitation protocol, which includes field collection and transfusion of whole blood. This protocol can serve as a template for others to use and adjust for their own military or civilian unit–specific needs and capabilities for care in austere environments.

Whole blood for hemostatic resuscitation of major bleeding.

Recent combat experience reignited interest in transfusing whole blood (WB) for patients with life‐threatening bleeding. US Army data indicate that WB transfusion is associated with improved or comparable survival compared to resuscitation with blood components. These data complement randomized controlled trials that indicate that platelet (PLT)‐containing blood products stored at 4°C have superior hemostatic function, based on reduced bleeding and improved functional measures of hemostasis, compared to PLT‐containing blood products at 22°C.