thromboplastin and Brain-Injuries

Polytraumatic injury results in tissue factor (TF) release from damaged cells. The acute coagulopathy of trauma (ACT) occurs early and results from significant tissue injury and tissue hypoperfusion. ACT is augmented by therapies resulting in acidemia, hypothermia, and hemodilution contributing to trauma-induced coagulopathy. Coagulopathy associated with traumatic brain injury (TBI) results from the interplay of numerous variables. Because of the high concentration of TF in brain tissue, TBI has been believed to be associated with a greater degree of coagulopathy compared with injury in other body systems. TBI has also recently been shown to cause platelet dysfunction. Platelet receptor inhibition prevents cellular initiation and amplification of the clotting cascade, limiting thrombin incorporation, and stabilization of clot to stop hemorrhage. Therefore, head injury in the presence of polytrauma does appear to augment ACT and warrants close monitoring and appropriate intervention.

Topics: Blood Coagulation Disorders; Brain; Brain Hemorrhage, Traumatic; Brain Injuries; Humans; Models, Biological; Multiple Trauma; Signal Transduction; Thromboplastin

The interaction of coagulation factors with the perivascular environment affects the development of disease in ways that extend beyond their traditional roles in the acute hemostatic cascade. Key molecular players of the coagulation cascade like tissue factor, thrombin, and fibrinogen are epidemiologically and mechanistically linked with diseases with an inflammatory component. Moreover, the identification of novel molecular mechanisms linking coagulation and inflammation has highlighted factors of the coagulation cascade as new targets for therapeutic intervention in a wide range of inflammatory human diseases. In particular, a proinflammatory role for fibrinogen has been reported in vascular wall disease, stroke, spinal cord injury, brain trauma, multiple sclerosis, Alzheimer's disease, rheumatoid arthritis, bacterial infection, colitis, lung and kidney fibrosis, Duchenne muscular dystrophy, and several types of cancer. Genetic and pharmacologic studies have unraveled pivotal roles for fibrinogen in determining the extent of local or systemic inflammation. As cellular and molecular mechanisms for fibrinogen functions in tissues are identified, the role of fibrinogen is evolving from a marker of vascular rapture to a multi-faceted signaling molecule with a wide spectrum of functions that can tip the balance between hemostasis and thrombosis, coagulation and fibrosis, protection from infection and extensive inflammation, and eventually life and death. This review will discuss some of the main molecular links between coagulation and inflammation and will focus on the role of fibrinogen in inflammatory disease highlighting its unique structural properties, cellular targets, and signal transduction pathways that make it a potent proinflammatory mediator and a potential therapeutic target.

Topics: Alzheimer Disease; Animals; Arthritis, Rheumatoid; Bacterial Infections; Blood Coagulation; Brain Injuries; Colitis; Fibrinogen; Humans; Inflammation; Kidney Diseases; Multiple Sclerosis; Muscular Dystrophy, Duchenne; Neoplasms; Pulmonary Fibrosis; Spinal Cord Injuries; Stroke; Thrombin; Thromboplastin; Vascular Diseases

Traumatic injury is a common cause of coagulopathy, primarily due to blood loss and hemodilution secondary to fluid resuscitation. Traumatic injury-associated coagulopathy often follows a course of transition from hyper- to hypocoagulable state exemplified in disseminated intravascular coagulation. The incidence of coagulopathy is significantly higher in patients with traumatic brain injury (TBI), especially those with penetrating trauma compared to injury to the trunk and limbs. This occurs despite the fact that patients with isolated TBI bleed less and receive restricted volume load of fluids. TBI-associated coagulopathy is extensively documented to associate with poor clinical outcomes, but its pathophysiology remains poorly understood. Studies in the past have shown that brain tissue is highly enriched in key procoagulant molecules. This review focuses on the biochemical and cellular characteristics of these molecules and pathways that could make brain uniquely procoagulant and prone to coagulopathy. Understanding this unique procoagulant environment will help to identify new therapeutic targets that could reverse a state of coagulopathy with minimal impacts on hemostasis, a critical requirement for neurosurgical treatments of TBI.

Topics: Animals; Blood Coagulation Disorders; Brain Hemorrhage, Traumatic; Brain Injuries; Endothelium, Vascular; Humans; Phosphatidylserines; Phospholipids; Platelet Activating Factor; Platelet Count; Thromboplastin

Topics: Adult; Anemia; Blood Transfusion, Autologous; Brain Injuries; Central Nervous System Neoplasms; Cesarean Section; Female; Humans; Intraoperative Period; Leukemia; Male; Neurosurgical Procedures; Plasmacytoma; Pregnancy; Prostatic Hyperplasia; Thromboplastin

Traumatic brain injury (TBI) initiates interrelated inflammatory and coagulation cascades characterized by wide-spread cellular activation, induction of leukocyte and endothelial cell adhesion molecules and release of soluble pro/antiinflammatory cytokines and thrombotic mediators. Resuscitative care is focused on optimizing cerebral perfusion and reducing secondary injury processes. Hypertonic saline is an effective osmotherapeutic agent for the treatment of intracranial hypertension and has immunomodulatory properties that may confer neuroprotection. This study examined the impact of hypertonic fluids on inflammatory/coagulation cascades in isolated head injury.. Using a prospective, randomized controlled trial we investigated the impact of prehospital resuscitation of severe TBI (GCS < 8) patients using 7.5% hypertonic saline in combination with 6% dextran-70 (HSD) vs 0.9% normal saline (NS), on selected cellular and soluble inflammatory/coagulation markers. Serial blood samples were drawn from 65 patients (30 HSD, 35 NS) at the time of hospital admission and at 12, 24, and 48-h post-resuscitation. Flow cytometry was used to analyze leukocyte cell-surface adhesion (CD62L, CD11b) and degranulation (CD63, CD66b) molecules. Circulating concentrations of soluble (s)L- and sE-selectins (sL-, sE-selectins), vascular and intercellular adhesion molecules (sVCAM-1, sICAM-1), pro/antiinflammatory cytokines [tumor necrosis factor (TNF)-alpha and interleukin (IL-10)], tissue factor (sTF), thrombomodulin (sTM) and D-dimers (D-D) were assessed by enzyme immunoassay. Twenty-five healthy subjects were studied as a control group.. TBI provoked marked alterations in a majority of the inflammatory/coagulation markers assessed in all patients. Relative to control, NS patients showed up to a 2-fold higher surface expression of CD62L, CD11b and CD66b on polymorphonuclear neutrophils (PMNs) and monocytes that persisted for 48-h. HSD blunted the expression of these cell-surface activation/adhesion molecules at all time-points to levels approaching control values. Admission concentrations of endothelial-derived sVCAM-1 and sE-selectin were generally reduced in HSD patients. Circulating sL-selectin levels were significantly elevated at 12 and 48, but not 24 h post-resuscitation with HSD. TNF-alpha and IL-10 levels were elevated above control throughout the study period in all patients, but were reduced in HSD patients. Plasma sTF and D-D levels were also significantly lower in HSD patients, whereas sTM levels remained at control levels.. These findings support an important modulatory role of HSD resuscitation in attenuating the upregulation of leukocyte/endothelial cell proinflammatory/prothrombotic mediators, which may help ameliorate secondary brain injury after TBI.. NCT00878631.

Topics: Adult; Analysis of Variance; Antigens, CD; Blood Coagulation; Brain Injuries; Cytokines; Dextrans; Enzyme-Linked Immunosorbent Assay; Female; Fibrin Fibrinogen Degradation Products; Glasgow Coma Scale; Humans; Inflammation; Leukocytes; Male; Middle Aged; Resuscitation; Saline Solution, Hypertonic; Statistics, Nonparametric; Thrombomodulin; Thromboplastin; Time Factors; Vascular Cell Adhesion Molecule-1

The potential pathophysiological role of circulating microparticles (MPs) has been recognized in various conditions, such as cardiovascular and thrombotic diseases. Traumatic brain injury (TBI) has a complex pathophysiology that involves coagulopathy and inflammation. We investigated endothelial-, platelet-, and leukocyte-derived microparticles (EMPs, PMPs, and LMPs, respectively) in 16 patients with severe isolated TBI. Arterial and cerebrovenous samples were taken repeatedly, during 1-72 h after injury. Subpopulations of MPs, exposing tissue factor (TF) and P-selection, were also studied. MP counts in cerebrovenous samples, irrespective of cellular origin, were higher in TBI cases, compared to healthy controls (peak levels of EMPs were approximately 7 times higher, PMPs 1.4 times higher, and LMPs 2 times higher, respectively; p<0.001 for all). MP counts declined sharply from high levels shortly after the trauma toward slightly elevated levels 72 h later. EMPs and PMPs exposing TF, as well as PMPs exposing P-selection, showed a transcranial gradient with higher concentration in cerebrovenous, compared to arterial, samples. In contrast, LMPs exposing TF were higher in arterial samples, suggesting accumulation of LMPs in the brain. We conclude that the pattern of circulating MPs is altered after TBI. PMPs exposing P-selection and EMPs exposing TF seem to be generated in the injured brain, whereas LMPs exposing TF are accumulated. The pathophysiological significance of these changes in MP pattern in TBI should be further investigated. Including MPs exposing brain-specific antigens in the assessment of brain injury would give further information of origin and likely give additional information of the size of the injury, given that the MP phenotypes investigated in the present study are not brain-specific markers.

Topics: Adult; Aged; Brain; Brain Injuries; Cell-Derived Microparticles; Female; Humans; Male; Middle Aged; P-Selectin; Thromboplastin; Young Adult

Topics: Antifibrinolytic Agents; Brain Injuries; Disseminated Intravascular Coagulation; Hemorrhage; Humans; Thromboplastin

Tissue thromboplastin (TTP) is an integral membrane protein contributing to coagulopathy after trauma of brain, which is a rich source of TTP.. A study was undertaken to establish the TTP content of various areas of normal brain and estimate the changes in TTP activity of brain in response to varying degrees of trauma.. Samples from different areas of brain of ten cadavers were used as controls and they were compared with contused brain tissue obtained after surgery in 25 head injury (HI) patients of varying severity.. In the study group, the TTP activity of the frontal, parietal, and temporal lobes after HI was significantly raised in contrast to that of the control group. The TTP activity was also significantly higher in the severe HI patients than those having moderate HI. The mode of injury and the time lapse after HI had no significant bearing on the TTP activity. Subjects above 40 years of age demonstrated a higher mean TTP activity after HI, though it was not statistically significant.. The study provides quantitative data on TTP activity of normal brain and highlights the role of TTP in coagulopathy following HI through its increased activity after HI, more so in the severe HI group.

Topics: Adolescent; Adult; Aged; Brain Chemistry; Brain Injuries; Craniocerebral Trauma; Female; Humans; Male; Middle Aged; Neurosurgical Procedures; Thromboplastin; Tomography, X-Ray Computed

A case is described of acute defibrination following blunt head injury in a patient with a Spitz-Holter drain. The cause of the disseminated intravascular coagulation is thought to be due to brain thromboplastins entering the systemic circulation through the Spitz-Holter drain, thus bypassing the blood-brain barrier.

Topics: Accidents, Traffic; Adolescent; Afibrinogenemia; Brain Injuries; Cerebrospinal Fluid Shunts; Disseminated Intravascular Coagulation; Female; Humans; Thromboplastin; Wounds, Nonpenetrating

This is an investigation into thromboplastin time, partial thromboplastin time, plasma thrombin time, fibrinogen, and platelets in 30 patients with severe brain injury over 7--14 days. Platelets showed a very marked initial decrease and a slow return to normal around the seventh day. Fibrinogen was initially lowered in most of the cases, and raised from the second day onward. Changes in the other laboratory values were less definite. Latent signs of consumption coagulopathy were not accompanied by bleeding disorders, or by disseminated intravascular coagulation at autopsy. The severity of laboratory value changes clearly correlated with the extent of brain damage, and was significantly higher when the patient did not survive the first week after injury.

Topics: Blood Cell Count; Blood Coagulation; Blood Platelets; Brain Injuries; Disseminated Intravascular Coagulation; Female; Fibrinogen; Humans; Male; Protease Inhibitors; Skull; Thrombin; Thromboplastin

Topics: Adult; Animals; Blood Coagulation; Brain; Brain Injuries; Brain Mapping; Cerebral Ventricle Neoplasms; Disseminated Intravascular Coagulation; Dogs; Factor VIII; Female; Humans; Oligodendroglioma; Postoperative Complications; Thromboplastin

Disseminated intravascular coagulation (DIC) developed in two patients following head trauma. Brain parenchyma and highly vascular connective tissue of the choroid plexus and meninges are important pools of systemic coagulation components. This is an important consideration in the treatment of head injury.

Topics: Accidents, Traffic; Adolescent; Autopsy; Brain; Brain Edema; Brain Injuries; Craniocerebral Trauma; Disseminated Intravascular Coagulation; Hematoma, Epidural, Cranial; Humans; Male; Prothrombin Time; Subarachnoid Hemorrhage; Thromboplastin

Topics: Blood Coagulation Disorders; Blood Coagulation Tests; Brain Injuries; Ethanol; Factor V; Fibrinogen; Fibrinolysis; Gels; Humans; Platelet Aggregation; Syndrome; Thromboplastin

Topics: Blood Coagulation Tests; Brain; Brain Injuries; Craniocerebral Trauma; Disseminated Intravascular Coagulation; Hemostasis; Humans; Thromboplastin

Topics: Blood Coagulation Tests; Blood Transfusion; Brain; Brain Injuries; Debridement; Disseminated Intravascular Coagulation; Heparin; Humans; Male; Middle Aged; Thromboplastin; Wounds, Gunshot