by Diffuse activation of the extrinsic coagulation pathway may lead to disseminated intravascular coagulation (DIC). to continued bleeding of microvessels fractured at the time of primary injury. This concept has given rise to the notion Oxantel Pamoate that continued bleeding might be due to overt or latent coagulopathy, prompting attempts to normalize coagulation with brokers such as recombinant factor VIIa. Recently, a novel mechanism was postulated to account for HPC that involves delayed, progressive microvascular failure initiated by the impact. Here we review the topic of HPC, we examine data relevant to the concept of a coagulopathy, and we detail emerging data elucidating the mechanism of progressive microvascular failure that predisposes to HPC after head trauma. Key words:coagulopathy, contusion, hemorrhage, traumatic brain injury == Introduction == Traumatic brain injury (TBI)is the most disabling of traumatic injuries, often leading to lifelong physical, cognitive, behavioral, and emotional impairments (Langlois et al.,2006; Selassie et al.,2008; Thurman et al.,1999). Nearly half of hospitalized survivors of TBI experience long-term disabilities (Selassie et al.,2008; Thurman et al.,1999; Zaloshnja et al.,2008). The lifetime costs of TBI in the United States, including Oxantel Pamoate medical costs and costs due to lost productivity, total an estimated $60 billion annually, constituting one of the largest expenditures in the health care system (Langlois et al.,2006; Selassie et al.,2008; Thurman et al.,1999). TBI encompasses numerous types of insults to the brain, with one of the most severe being a hemorrhagic cerebral contusion. TBI associated with cerebral contusion is usually a frequent cause of death and disability in trauma victims who reach the hospital alive (Alahmadi et al.,2010). Excellent reviews around the natural history of cerebral contusions have been published (Alahmadi et al.,2010), but our purpose is different. Here we focus specifically around the phenomenon of hemorrhagic progression of a contusion (HPC), a secondary injury process that designates the Oxantel Pamoate enlargement or new appearance of a parenchymal hemorrhagic contusion due to delayed bleeding. Not only does HPC greatly exacerbate an already grave situation, but most frustrating to healthcare providers and patients, it does so during the several hours or early days after trauma when patients are already hospitalized. Ample opportunity would be available to intervene if proper intervention could be devised. In this review, we begin by documenting the characteristic features of HPC. Then we examine two mechanisms that have been implicated in its development. First, we consider the conventional explanation, that an explicit or latent coagulopathy leads to continued or delayed bleeding of microvessels fractured at the time of primary injury. Next we consider a novel, recently discovered mechanism postulating that microvessels in the region of injury (penumbra) receive kinetic energy from the impact that is not sufficient to fracture them, but is sufficient to induce a series of maladaptive molecular events that eventually results in their structural failure, leading to delayed formation of petechial hemorrhages which then coalesce to produce hemorrhagic progression. Distinguishing between these two mechanisms is usually important, because the implications for treatment are quite different. For the first mechanism, treatment must be aimed at normalizing coagulation, whereas for the second, treatment must block the maladaptive molecular events in microvascular endothelial cells. == Primary versus secondary injury == MGC102762 Tissue damage after head trauma is due to primary injury plus secondary injury. Primary injury refers to the physical destruction of tissues that occurs within moments of impact. Kinetic energy deposited by the impact causes shearing of the tissues. The primary injury ruptures neurons, astrocytes, and oligodendrocytes, causing their immediate necrotic death. Necrotic cell death releases intracellular substances (e.g., excitatory amino acids and heat-shock proteins) that incite secondary injury responses. The primary injury also ruptures microvessels, causing extravasation of blood and the loss of function of those vessels, which leads to ischemia. Breakdown products of extravasated blood are extremely toxic to central nervous system (CNS) cells and also incite secondary injury responses. Secondary injury responses are numerous (Table 1). All lead, Oxantel Pamoate more or less, to further tissue injury that worsens the primary injury. Many secondary injury responses are simply the natural consequence of primary tissue damage, such as the release of excitotoxic substances, free radical damage from blood breakdown products, and ischemia due to loss of microvessels. Other.
