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The pathophysiologic course of sepsis involves the release of cyto- and chemokines in addition to the activation of endothelial and neutrophil cells, initiating a cascade of cell-surface interactions. Activation of the coagulation system has been characterized by widespread intravascular fibrin deposition and platelet aggregation (disseminated intravascular coagulation, DIC) with subsequent microvascular and tissue injury, ultimately leading to multiple organ failure (MOF) and death. The contributing role of platelets in the pathophysiology of sepsis and related organ dysfunction is not entirely clear, although the degree and duration of thrombocytopenia, as well as the net change in the platelet count, are important determinants for survival [, ]. Of note, the involvement of platelets in sepsis-associated coagulopathy was already studied by many groups more than 25 years ago, focusing on the interaction of platelets with endotoxin, and the role of thrombin generation and DIC on platelet function [, ]. However, regarding the various pathogenic mechanisms that have recently been implicated in the activation of coagulation in sepsis, a reassessment of the role of platelets is needed.

Trauma is an increasingly common cause of death of modern society. Death caused by trauma is rapidly surpassing the number of deaths due to stroke or cardiovascular disease. Uncontrolled bleeding is the leading cause of early in-hospital mortality (within 48 h of admission) and the second leading cause of pre-hospital death, accounting for 40% and 45% of the fatalities, respectively []. Massive hemorrhage after traumatic injury is frequently a combination of surgical and coagulopathic bleeding. Coagulopathic bleeding results from impairments in platelet function, fibrin formation, or enhanced degradation, or combinations of all these mechanisms. Understanding the exact etiology is crucial for successful management of this pathology. Early coagulopathy post-injury is observed in 25 to 36% of trauma victims upon admission to the emergency department [, ] and correlates with the severity of trauma. It is associated with an increased risk of mortality beyond the expected figures from the severity of the injury []. Coagulopathy can develop during, and be the result of the ‘traditional aggressive’ fluid resuscitation of hemorrhagic shock. It can also develop late, due to surgical complications such as sepsis or multiple organ failure (MOF). This chapter describes the pathophysiology of coagulopathy in various phases of trauma and discusses the mechanisms that can contribute to it.

Trauma is a serious global health issue in Western Countries and the leading cause of death during the first four decades of life [,]. Because injury is frequent among the younger population, life-years lost are greater from injury (on average 36 years lost per death) than from cardiovascular or neoplastic disease [,]. In Italy, there are 1,143,305 trauma admissions every year (9.3% of all hospital admissions), with 25,038 (2.19%) trauma patients being admitted to intensive care units (ICUs) (data from Italian Ministry of Health). Trauma deaths before and after hospital admission are 18,000 per year. Acute blood loss has been reported to be the principal cause of immediate or early trauma death –. In an autopsy study on 255 consecutive trauma deaths [], hemorrhage alone or combined with severe head trauma, was the cause of death in 70% of cases. Significantly, most of these deaths occurred during the first phases of pre-hospital or hospital care. The length of time between injury and death was less than one hour in 66.5% and from 1 to 6 hours in 24.6% of cases. In European countries, owing to the prevalence of blunt trauma, causes of unstable hemodynamics are mainly pelvic ring and extremity fractures with extensive soft tissue destruction, followed by abdominal injuries (Fig. 1). Advances in trauma care, such as improved transportation systems, hypotensive resuscitation, strategies of damage control in emergency surgery, angiographic embolization procedures, all increase the chances of survival of the hemorrhagic patient. Nevertheless, hemodynamic instability often requires infusion of liters of crystalloid and colloid solutions and transfusion of several units of packed red cells, leading to consumption and dilution of clotting factors.

One in 10 deaths worldwide is the result of trauma and it is estimated that, by the year 2010, annual trauma-related mortality worldwide will increase to 8.4 million []. While resuscitation of trauma patients has improved dramatically in recent years, uncontrollable bleeding still accounts for 39% of trauma deaths and is considered to be the leading cause of potentially preventable death following major trauma []–[].

Advances in surgical and critical care medicine frequently parallel the course of armed conflict. Indeed, surgery is a specialty born of warfare and will continue to drive advancements as mankind finds new and more lethal methods of combat. As hemorrhage is far and away the leading cause of potentially survivable death on the battlefield, the methods of resuscitation and blood transfusion continue to evolve. The critical role that blood plays in resuscitation of the critically injured patient was first explored during World War I for the treatment of ‘wound shock’. Type O whole blood was collected in sterile glass bottles containing citrate and transfused into patients prior to surgery. During the years following World War I, blood component fractionation became available, blood banking was initiated, and the transfusion of packed red blood cells (RBCs), fresh frozen plasma (FFP) and platelets became a mainstay of the trauma management paradigm. However, in times of war the variable availability of short-lived platelets, FFP, and cryoprecipitate inevitably leads back to the resurrection of fresh whole blood transfusion. Fresh whole blood, though not without some risk, restores the hemostatic mechanism and provides volume and oxygen-carrying capacity.

Plasma substitutes, such as crystalloid or colloid solutions are frequently used in bleeding patients or in situations with a high risk of bleeding such as trauma or during surgery. There is ample evidence that these agents may affect blood coagulation and platelet function [], although some authors, referring to thromboelastography studies, have suggested that hemodilution results in a hypercoagulable state []. These findings, however, have been disputed. In particular, all three distinct classes of artificial colloids (i.e., dextrans, hydroxyethyl starches [HES], and gelatins) have been associated with derangements of the hemostatic system, although the clinical significance of these derangements is a matter of debate []. In this chapter, we will focus on the anti-hemostatic effects of various volume replacement fluids on platelet function and blood coagulation.

Transfusions are regularly employed in the care of the critically ill. While the transmission of infectious agents and clerical errors have long been major concerns, a more common non-infectious complication of transfusion, namely acute lung injury/acute respiratory distress syndrome (ALI/ARDS), has been neglected. Indeed, during the past several years, post-transfusion ALI/ARDS (transfusion-related acute lung injury — TRALI) has become the leading cause of transfusion-related death in the United States []. It likely occurs much more frequently than previously estimated. With skyrocketing health care costs and the continuous emphasis on improvement in patient care, it is of paramount importance to better define this transfusion-related phenomenon and to design effective strategies for its prevention. Several investigator groups have been on the leading edge in the quest to clearly elucidate this disease entity and define its prevalence.

Anemia is a common pathology in critically ill patients and about one third of intensive care unit (ICU) patients receive a red blood cell (RBC) transfusion at some point during their ICU stay []. At ICU admission, the mean hemoglobin concentration of critically ill patients is 11 g/dL, while in 60% and 30% of such patients, the mean hemoglobin concentration is less than 12 and 10 g/dL, respectively [, ].

Hospitalized patients who experience sudden, or unanticipated, physiological deterioration and subsequent cardiorespiratroy arrest have very poor outcomes. Studies have reported varying results in mortality following cardiac arrest, but most have historically placed the level of survival to discharge at around 15%, with some recent studies placing the figure closer to 30% [, ]. In addition, the institutional and patient costs of an arrest event are quite high []. Patients who undergo an unexpected arrest consume extensive personnel resources, receive more medications and other therapies, and spend more time in intensive care units (ICUs). One study has estimated that in-hospital cardiopulmonary resuscitation (CPR) programs cost $ 400,000 per life saved []. Other investigations have concluded that much of the morbidity and mortality associated with such events is preventable . Studies have estimated that up to 84% of patients who go on to a cardiorespiratory arrest have measurable evidence of deterioration in the eight hours prior to their event []. If these symptoms and signs could be correctly identified and acted upon, a portion of these less than optimal outcomes might be avoided.

A new approach to resuscitation of individuals with out-of-hospital cardiac arrest due to ventricular fibrillation or pulseless ventricular tachycardia was implemented in Tucson Arizona in 2003 and in 2004 this approach was further modified and implemented in the Rock and Walworth counties of Wisconsin []–[]. This approach is now called Cardiocerebral Resuscitation. At the time of its development, it was a dramatic departure from the then traditional technique of cardiopulmonary resuscitation (CPR) endorsed by the American Heart Association and the international community in “Guidelines 2000” []. This new approach to out-of-hospital cardiac arrest is extremely important, for when the principles of cardiocerebral resuscitation were utilized in the pre-hospital care of adults with a witnessed arrest and an initially shockable rhythm, a marked and statistically significant improvement in survival was observed (Kellum et al. personal communication).