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Figure1: Tissue thromboplastin activity in patients with head injury according to the severity of injury
Source publication
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 o...
Citations
... The brain parenchyma is rich in thromboplastin, and its secretion increases significantly in the case of an injury or stress. Consequently, when the brain parenchyma is exposed to plasma, thromboplastin or procoagulant tissue factor combines with factor VII of the extrinsic clotting cascade and activates the coagulation pathway [6,7]. ...
... The incidences of DVT, SVT, and VTE were 4.6%, 9.6%, and 12.2%, respectively. The logistic regression model did not find the indication for craniotomy/craniectomy to be significant in predicting VTE incidence, despite the relationships of TBI, brain tumors, and brain surgery with hypercoagulability proposed in the literature [6][7][8][9][10][11][12][13]. However, this model showed that increasing the number of days between surgery and the administration of anticoagulants significantly increased the risk of VTE incidence. ...
Background
Venous thromboembolism (VTE) is quite common among post-operative neurosurgical patients. This study aims to identify the incidence of deep vein thrombosis (DVT) and superficial vein thrombosis (SVT) among post-craniotomy/craniectomy patients and further evaluate established hypercoagulability risk factors such as trauma, tumors, and surgery.
Methodology
This single-center retrospective study investigated 197 patients who underwent a craniotomy/craniectomy. The incidences of DVT and SVT were compared, along with laterality and peripherally inserted central catheter (PICC) line involvement. A multivariate logistic regression analysis was conducted to identify risk factors for post-craniotomy/craniectomy VTE. This model included variables such as age, post-operative days before anticoagulant administration, female sex, indications for surgery such as tumor and trauma, presence of a PICC line, and anticoagulant administration.
Results
Among the 197 post-craniotomy/craniectomy patients (39.6% female; mean age 53.8±15.7 years), the incidences of DVT, SVT, and VTE were 4.6%, 9.6%, and 12.2%, respectively. The multivariate logistic regression analysis found that increasing the number of days between surgery and administration of anticoagulants significantly increased the risk of VTE incidence (odds ratio 1.183, 95% CI 1.068-1.311, p = 0.001).
Conclusions
Contrary to existing evidence, this study did not find trauma or the presence of tumors to be risk factors for VTE. Future prospective studies should assess VTE risk assessment models such as “3 Bucket” or “Caprini” to develop universal guidelines for administering anticoagulant therapy to post-craniotomy/craniectomy patients that consider the timing of post-operative therapy initiation.
... Prior studies have documented an increased INR after TBI, some suggesting an association with progressive hemorrhagic injury [12,13]. Although prior studies have not fully described the dynamic course of the post-TBI INR elevation, they have reported an increase in the tissue thromboplastin activity, primarily in the frontal, parietal, and temporal lobes [14]. Penetrating injuries to these regions can, therefore, trigger a significant and prolonged hematological response through a direct interaction between the damaged brain tissue and blood. ...
Introduction
Penetrating ballistic brain injury (gunshot traumatic brain injury or GTBI) is associated with a high mortality. Admission Glascow Coma Scale (GCS), injury severity score and neurological findings, cardiopulmonary instability, coagulopathy and radiological finding such as bullet trajectory and mass effect are shown to predict survival after GTBI. We aimed to examine the dynamics of the observed coagulopathy and its association with outcome.
Methods
In this single-centered retrospective cohort study, we examined 88 patients with GTBI between 2015 and 2021. Variables analyzed include patient age; temperature, hemodynamic and respiratory variables, admission Glasgow Coma Scale (GCS); injury severity score (ISS); head abbreviated injury scale (AIS); Marshall, Rotterdam, SPIN and Baylor scores, and laboratory data including PTT, INR and platelet count. Receiver operating characteristic analysis was conducted to evaluate the performance of the predictive models.
Results
The average age of our sample was 28.5 years and a majority were male subjects (92%). Fifty-four (62%) of the patients survived to discharge. The GCS score, as well as the motor, verbal, and eye-opening sub-scores were higher in survivors (P < 0.001). As was expected, radiologic findings including the Marshall and Rotterdam Scores were also associated with survival (P < 0.001). Although the ISS and Head AIS scores were higher (P < 0.001), extracranial injuries were not more prevalent in non-survivors (P= 0.567). Non-survivors had lower platelet counts and elevated PTT and INR (P < 0.001) on admission. PTT normalized within 24 h but INR continued to increase in non-survivors. SPIN score, which includes INR, was a better predictor for mortality than Rotterdam, Marshall, and Baylor etc.
Conclusion
Progressively increasing INR after GTBI is associated with poor outcome and may indicate consumption coagu-lopathy from activation of the extrinsic pathway of coagulation and metabolic derangements that are triggered and sustained by the brain injury. The SPIN score, which incorporates INR as a major survival score component, outperforms other available prediction models for predicting outcome after GTBI.
... The brain contains high tissue factor (TF) which is a cofactor for factor VIIa in the extrinsic coagulation cascade [65], [66]. In TBI pathophysiology, TF is released following trauma and activate coagulation pathway [67], [68], [69]. Replacement of tissue thromboplastin activate extrinsic cascade to form fibrin clot [60], [70]. ...
BACKGROUND: Secondary traumatic brain injury (TBI) is injury to the brain following primary TBI because of neuroinflammation as consequences of neuronal and glial cell injury which cause release of various inflammation cytokine and chemokine. Biomarker examination to predict the severity of secondary TBI is important to provide appropriate treatment to the patient. This article reviews possibility several common laboratory parameter such as monocyte-to-lymphocyte ratio (MLR), mean platelet volume-to-platelet count (PC) ratio (MPV-PCR), c-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) to predict severity of secondary TBI. LITERATURE REVIEW: TBI activates microglia which increase infiltration and proliferation of monocyte. Neuroinflammation also increases thrombopoiesis which leads to increase megakaryocytes production. In the other hand, due to disruption of brain blood vessels because of trauma, coagulation cascade is also activated and leads to consumptive coagulopathy. These are reflected as high monocyte count, low PC, and high MPV. Lymphocyte count is reported low in TBI especially in poor outcome patients. CRP is an acute phase reactant that increased in inflammation condition. In TBI, increased production of Interleukin-6 leads to increase CRP production. In head injured patients, ESR level does not increase significantly in the acute phase of inflammation but last longer when compared to CRP. CONCLUSION: MLR, MPV-PCR, CRP, and ESR could be predictor of severity in secondary TBI.
... Typically expressed in vascular walls and astrocytes, stimulated and activated following injury [1]. Thromboplastin (tissue thromboplastin-TTF), an initiator of the coagulation cascade, is highly expressed in brain tissue and in vascular endothelial cells and the surface of leucocyte in head injury patients [2]. Brain is rich in PAF (platelet-activating factor). ...
Background
Post-traumatic cerebral venous sinus thrombosis (CVST) - incidence is rising during the last two decades, partly due to advanced imaging technologies and partly due to accidents caused by high-velocity vehicles.
Case series
During a period from January 2020 to September 2020, we had 264 cases of head injury patients. On average, we receive 30 head injury cases per month, among which 50 % would be severe head injury cases. We documented ten CVST cases among them.
Diagnosis and management
In severe head injuries with suspicion, CT brain with contrast done immediately to diagnose CVST. After 48 hours of admission, worsening of GCS, increased severity of headache despite adequate management, worsening of CT findings as an increase in edema, and hemorrhagic transformation are all indications for repeat CT brain with contrast. Management of CVST patients done with enoxaparin 40 mg twice a day/ 1.5 mg per kg in a day, for a duration of ten to fourteen days. Anticoagulants started only after 48 hours of trauma.
Conclusion
Early diagnosis of CVST in severe head injury patients and treatment started early(after 48 hours of trauma) will help to prevent morbidity and mortality.
... Intramural hemorrhage secondary to rupture of sinusoids at the site of entry of draining veins, and extension of thrombus from injured scalp and emissary veins and release of thromboplastin is also believed to contribute to a locally procoagulant state, which may predispose to venous thrombosis. 2,3 The clinical presentation of venous thrombosis is subacute and clinical features depend on the involvement of the sinus or cortical veins. Sinus involvement usually presents with features of raised intracranial pressure whereas cortical vein thrombosis may present with focal neurological deficits or seizures. ...
Post traumatic Sinus/cerebral venous thrombosis is a rare entity. A high index of suspicion is required as the prognosis is poor in this clinical setting, in view of the effects of the head injury. We report 2 cases of the patient worsening acutely after initial recovery from trauma. The etiology and pathogenesis in such cases are varied and hypothetical with no definite underlying cause identified. Cerebral venous thrombosis (CVT) as an etiology of headache is not always easy to diagnose unless suspected, and in any patient with head injury and delayed deterioration after initial recovery, post traumatic Cerebral venous thrombosis should be kept as a differential diagnosis.
... In addition, tissue have a prognostic value in traumatic brain injury [25,26]. In our study, thromboplastin activity was significantly increased in r-OBI group compared with control in both cortex and cerebellum (P < 0.01, P < 0.05, respectively) (Fig. 3D, H) indicating an increased susceptibility for bleeding. ...
Background & aim:
Overpressure blast-wave induced brain injury (OBI) and its long-term neurological outcome pose significant concerns for military personnel. Our aim is to investigate the mechanism of injury due to OBI.
Methods:
Rats were divided into 3 groups: 1) Control, 2) OBI (exposed 30psi peak pressure, 2-2.5ms), 3) Repeated OBI (r-OBI) (three exposures over one-week period). Lung and brain (cortex and cerebellum) tissues were collected at 24h post injury.
Results:
The neurological examination score was worse in OBI and r-OBI (4.2±0.6 and 3.7±0.5, respectively) versus controls (0.7±0.2). A significant positive correlation between lung and brain edema was found. Malondialdehyde (index for lipid peroxidation), significantly increased in OBI and r-OBI groups in cortex (p <0.05) and cerebellum (p <0.01-0.001). The glutathione (endogenous antioxidant) level decreased in cortex (p <0.01) and cerebellum (p <0.05) of r-OBI group when compared with the controls. Myeloperoxidase activity indicating neutrophil infiltration, was significantly (p <0.01-0.05) elevated in r-OBI. Additionally, tissue thromboplastin activity, a coagulation marker, was elevated, indicating a tendency to bleed. NGF and NF-ĸB proteins along with Iba-1 and GFAP immunoreactivity significantly augmented in the frontal cortex demonstrating microglial activation. Serum biomarkers of injury, NSE, TNF-alpha and leptin, were also elevated.
Conclusion:
OBI triggers both inflammation and oxidative injury in the brain. This data in conjunction with our previous observations suggests that OBI triggers a cascade of events beginning with impaired cerebral vascular function leading to ischemia and chronic neurological consequences.
... In patients with severe ischemic brain damage, the blood-brain barrier is disrupted, 51 and massive amounts of TF are released into systemic circulation, resulting in activation of the extrinsic pathway of blood coagulation. [52][53][54] It has been shown that the level of brain damage is associated with the amount of TF that is released. 55,56 Also, ischemic stroke patients have increased TF-bearing microparticles 57 and TF expression on monocytes. ...
Objective:
Obstructive thrombi or thrombotic emboli are the pathogenic basis of ischemic stroke. In vitro blood clots and in vivo thrombi can undergo platelet-driven contraction (retraction), resulting in volume shrinkage. Clot contraction can potentially reduce vessel occlusion and improve blood flow past emboli or thrombi. The aim of this work was to examine a potential pathogenic role of clot contraction in ischemic stroke.
Approach and results:
We used a novel automated method that enabled us to quantify time of initiation and extent and rate of clot contraction in vitro. The main finding is that clot contraction from the blood of stroke patients was reduced compared with healthy subjects. Reduced clot contraction correlated with a lower platelet count and their dysfunction, higher levels of fibrinogen and hematocrit, leukocytosis, and other changes in blood composition that may affect platelet function and properties of blood clots. Platelets from stroke patents were spontaneously activated and displayed reduced responsiveness to additional stimulation. Clinical correlations with respect to severity and stroke pathogenesis suggest that the impaired clot contraction has the potential to be a pathogenic factor in ischemic stroke.
Conclusions:
The changeable ability of clots and thrombi to shrink in volume may be a novel unappreciated mechanism that aggravates or alleviates the course and outcomes of ischemic stroke. The clinical importance of clot or thrombus transformations in vivo and the diagnostic and prognostic value of this blood test for clot contraction need further exploration.
... 151,152 It is postulated that the widespread injury to brain parenchyma leads to a massive release of TF, which promotes DIC. 153 Another theory suggests that activated platelets shed procoagulant microparticles, which provide a surface for coagulation and may promote both hyper-and hypocoagulability 154 from activation of coagulation followed by factor consumption. 150,155 Another contributing mechanism is platelet activation and dysfunction, which can occur despite a normal platelet count. ...
Coagulopathy, defined as impaired clot formation, is common in intensive care units (ICUs). Many physiological derangements lead to dysfunctional hemostasis in the ICU; most of these are acquired rather than congenital. Coagulopathies in the ICU are often related to systemic diseases, autoimmune dysfunction, acute infection, organ dysfunction, therapeutic medications, and/or other medical treatments. A significant complication of coagulopathy in the critically ill is major bleeding, defined as fatal hemorrhage, hemodynamic instability, transfusion requirement, or intracranial hematomas. Coagulopathy in the ICU often poses complex management dilemmas, especially when coagulopathy coexists with a thrombotic state. Coagulopathy associated with intracerebral hemorrhage (ICH) bears directly on neurologic prognosis and functional outcome. There is a paucity of high-quality evidence for the management of coagulopathies in neurocritical care; however, data derived from studies of patients with ICH may inform treatment decisions. This article focuses on acquired conditions such as pharmacological therapies, organ failure, and platelet dysfunction that are often associated with defective clot formation in the ICU that result in or exacerbate ICH.
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... This activation of tissue factors affects the blood coagulation disorder by inducing changes in blood coagulation factors. 22) Factor X is involved in intrinsic and extrinsic pathways, and factor V acts as a cofactor. In this study, factor V and factor X were reduced in group A. It appeared that factor V and factor X were reduced due to induction of a localized wasting blood coagulation disorder from the excessive coagulation state induced by intracerebral hemorrhage in group A. Thus, the size of the hematoma increased due to failure to carry out appropriate coagulation. ...
Objective
The objective of this study was to determine the correlations between changes in thrombogenesis or thrombolysis related factors, and the acute increase of a spontaneous intracerebral hemorrhage (sICH).
Materials and Methods
From January 2009 to October 2011, 225 patients with sICH were admitted to our hospital within 24 hours of onset. Among them, 111 patients with hypertensive sICH were enrolled in this study. Thrombogenic or thrombolytic factors were checked at admission. The authors checked computed tomography (CT) scans at admission and followed up the next day (between 12-24 hours) or at any time when neurologic signs were aggravated. Cases in which the hematoma was enlarged more than 33% were defined as Group A and the others were defined as Group B.
Results
Group A included 30 patients (27%) and group B included 81 patients (73%). Factors including activated partial thromboplastin time, prothrombin time, fibrinogen, and D-dimer showed a greater increase in group A than in group B. Factors including antithrombin III, factor V, and factor X showed a greater increase in group A than in group B.
Conclusion
Based on the results of this study, it seems that the risk of increase in hematoma size can be predicted by serum thrombogenic or thrombolytic factors at admission.
... The mean PTT was prolonged to 41.1 seconds and the mean prothrombin ratio was reduced to 66.5%. One possible explanation is that a severe head injury caused a coagulopathy because of expression of tissue thromboplastin and tissue factor from the injured brain [19][20][21]. Another explanation could be that elderly patients are more likely to be taking anticoagulant medication. ...
Demographic change is expected to result in an increase in cases of severely injured elderly patients. To determine special considerations in treatment and outcome, patients aged 75 years and older were studied.
All patients in the included age group with an Injury Severity Score (ISS) ≥ 16 upon primary admission to hospital between July 2002 and December 2011 were included in this mortality analysis. The data used for this study was gained partly from data submitted to the German Trauma Register and partly from patients’ hospital records. A comparison between survivors and decedents was performed, as well as age-adjusted and ISS-adjusted analyses. The odds ratio and relative risk were used to determine predictors for mortality.
One-hundred eight patients met the inclusion criteria. The overall mortality proportion was 57.4%. The decedents were more severely injured (ISS 26 vs. 20, p < 0.001) and suffered more severe head traumas (GCS 4 vs. 12, p < 0.001; AIS head 5 vs. 4, p = 0.006). No differences were found in vital parameters measured at the accident scene or trauma room. Decedents had deranged coagulation with a prolonged PTT (41.1 sec vs. 27.6 sec, p = 0.008) and reduced prothrombin ratio (66.5% vs. 82.8%, p = 0.016).
Only 17.1% of patients presenting an ISS > 25 survived, suggesting that an injury of such severity is hardly survivable in the subject age group.
Predictors for mortality were: ISS > 25, GCS < 9, PTT > 32.4 seconds, prothrombin ratio < 70%, AIS head > 3, and Hb < 12 g/dl.
The treatment of severely injured elderly patients is challenging. The most common cause of accident is falling from less than 3 m with head injuries being determinant. We identified deranged coagulopathy as an important predictor for mortality, suggesting rapid normalization of coagulation might be a key to reducing mortality.
