Subscribe to RSS
DOI: 10.1055/s-0044-1780494
Predicting Progressive Hemorrhagic Injury Following Traumatic Brain Injury by the Evaluation of D-Dimer/Fibrinogen Ratio
Abstract
Background Prognosis of traumatic brain injury (TBI) significantly depends on the incidence of progressive hemorrhagic injury (PHI). The present study was conducted to assess whether D-dimer/fibrinogen ratio can predict PHI among the patients with TBI.
Materials and Methods A total of 150 patients were included in this retrospective study; among them 72 had PHI and 78 did not have PHI. Demographic, clinical, radiological, and laboratory parameters including plasma D-dimer and plasma fibrinogen levels and subsequently D-dimer/fibrinogen ratio were evaluated. Independent t-test, Mann–Whitney U test, chi-square test, Fisher's exact test, and multivariate logistic regression were used for statistical analysis.
Results Age, injury time, first computed tomography time, Glasgow Coma Scale scores, unreactive pupils, abnormal cisterns, midline shift above 5 mm, skull base fracture, epidural hematoma, subdural hematoma, intraventricular hemorrhage, cerebral hematoma, brain contusion, plasma D-dimer concentration, plasma fibrinogen concentration, and D-dimer/fibrinogen ratio vary significantly between PHI and non-PHI groups (p < 0.05). Multivariate logistic regression showed that the Glasgow Coma Scale score (odds ratio [OR], 0.531; 95% confidence interval [CI], 0.436–0.648; p = 0.004) and D-dimer/fibrinogen ratio (OR, 3.784; 95% CI, 2.086–6.867; p = 0.027) were the two independent predictors for PHI.
Conclusion D-dimer/fibrinogen ratio is a useful parameter in predicting the incidence of PHI among the patients with TBI.
#
Keywords
D-dimer/fibrinogen ratio - Glasgow Coma Scale - plasma fibrinogen - traumatic brain injury - progressive hemorrhagic injuryIntroduction
Despite advancements in prevention and treatment, traumatic brain injury (TBI), a serious public health issue, remains a leading cause of disability and mortality in every part of the world. It has surpassed several diseases as the leading cause of death and disability due to its increasing incidence around the globe.[1] One-third to one-half of all trauma-related deaths are attributable to TBI.[2] [3] [4] One million people die and around 1.5 to 2.0 million people are reportedly injured each year in India.[5]
The imbalance between procoagulant and anticoagulant factors, platelets, endothelial function, and fibrinolysis has been documented to cause acquired coagulation disorders in TBI.[6] It has been found that aberrant coagulation factors, such as a high prothrombin time and a low platelet (PLT) count, can predict the outcome of a TBI.[7] The function of D-dimer, a byproduct of fibrinogen (Fg) breakdown, in TBI attracted a lot of attention in recent times. An abnormal D-dimer level may indicate an imbalance in the coagulation and fibrinolytic systems, which could change how TBI patients respond to treatment.[8] Researchers found that a greater D-dimer level was linked to a higher risk of progressive hemorrhagic injury (PHI); however, according to other experts the relationship was not statistically significant.[9] [10] [11] [12]
The present study aimed to investigate whether D-dimer/Fg ratio (D/F ratio) can predict PHI among the patients with TBI.
#
Materials and Methods
Study Population
After obtaining the approval from the institutional ethical committee, records of patients with TBI from January 2018 to December 2022 were assessed in a tertiary care hospital in North India. Patients who were admitted within 6 hours after trauma with a highest abbreviated injury score of 3 or less and at least two computed tomography (CT) scans within 24 hours of admission were included in the study. Patients with known coagulation disorders, such as deep venous thrombosis, pulmonary embolism (PE), and myocardial infarction, or under anticoagulant therapies and previous medical history of malignancy, uremia, and liver cirrhosis were excluded from the study. Initially, 186 patients were selected for the study but after excluding 36 patients as per the exclusion criteria, finally 150 patients were included in the study and their data were analyzed. Among them 72 had PHI and 78 did not have PHI.
#
Methodology
Patients with TBI had their records examined. Demographic parameters like age, sex, habit of smoking, and alcoholism, comorbidities like hypertension and diabetes mellitus, and cause and duration of the injury were noted. During the clinical examination, light reflex of pupils, time from injury to first CT scan, time from first to second CT scan, and trauma-related positive radiological appearances (abnormal cisterns, midline shift, skull-cap fracture, skull base fracture, epidural hematoma, subdural hematoma, subarachnoid hemorrhage, intraventricular hemorrhage, cerebral hematoma, brain contusion, and pneumocephalus) and Glasgow Coma Scale (GCS) score were noted. PHI was defined as the development of additional lesions or a noticeably larger hemorrhagic lesion(s) compared to the initial postinjury CT scan, with a minimum increase of 25% and a maximum increase of 50%.[13] Following laboratory data were also collected: plasma D-dimer concentration and plasma Fg concentration at time of admission. The D/F ratio was calculated as plasma D-dimer concentration (mg/L) divided by plasma Fg concentration (g/L).
#
Statistical Analysis
Data were tabulated in Microsoft Excel and analyzed using the SPSS (SPSS, Inc., Chicago, Illinois, United States) software. Normality of the data was assessed using Kolmogorov–Smirnov and Shapiro–Wilk test. The continuous variables which were found to be normally distributed have been presented with mean and standard deviation and compared using the independent t-test. The continuous variables which were not found to be normally distributed have been presented with median with quartile range (25th, 75th) and compared using the Mann–Whitney U test. The categorical variables have been presented with frequency and percentage and compared using the Pearson chi-square test or Fisher's exact test. A binary logistic regression model was applied to determine the predictors for PHI. A p-value of 0.05 or less was considered as statistically significant.
#
#
Results
[Table 1] shows the details of the demographic, clinical, radiological, and laboratory parameters of PHI and non-PHI groups. Among the demographic parameters, only the age of the patients in the PHI group significantly vary from the non-PHI group (p = 0.041). Among the clinical parameters, injury time, first CT time, and GCS score were significantly lower ([Fig. 1]) and the incidence of unreactive pupils was significantly higher among the PHI group (p = 0.008, p = 0.019, p < 0.001, and p < 0.001, respectively). Among the radiological findings, incidences of abnormal cisterns, midline shift above 5 mm, epidural hematoma, subdural hematoma, cerebral hematoma, and brain contusion were significantly higher among the PHI group (p < 0.001, p < 0.001, p = 0.031, p = 0.044, p = 0.015, and p = 0.027, respectively).
Abbreviations: CT, computed tomography; NS, not significant; PHI, progressive hemorrhagic injury.
Therefore, the factors associated with PHI were found to be age, injury time, first CT time, GCS scores, unreactive pupils, abnormal cisterns, midline shift above 5 mm, skull base fracture, epidural hematoma, subdural hematoma, intraventricular hemorrhage, cerebral hematoma, brain contusion, plasma D-dimer concentration, plasma Fg concentration, and D/F ratio. [Table 2] shows the results of multivariate analysis where the aforementioned variables were analyzed which indicates that the GCS score and D/F ratio were independent risk factors for the incidence of PHI.
Abbreviations: CI, confidence interval; CT, computed tomography; NS, not significant; OR, odds ratio; PHI, progressive hemorrhagic injury.
#
Discussion
With high prevalence and mortality, the importance of timely diagnosis of PHI with good sensitivity and specificity is important. Several factors, such as older age, male gender, poor GCS, and the presence of spot sign on CT angiography and coagulopathy, have been implicated as impact factors of intracranial hemorrhage progression.[10] [13] [14] [15] [16] [17] [18] [19] [20] Repeat CT scan is time-consuming and costly, addressing the associations between the abnormal blood tests and PHI would be of great value for which these laboratory test become meaningful; these parameters carry the most important weight for predicting PHI.
Blood clotting happens physiologically when Fg is converted into fibrin, which binds to trapped cellular components. D-dimer, a breakdown product of cross-linked fibrin in the plasma, is produced as a result of thrombin activation and the hybrid impact of plasmin. In response to increased coagulation activity, fibrinolysis is upregulated, which raises the level of D-dimer. D-dimer has been demonstrated to rise in peripheral blood from patients with disorders that affect the central nervous system, such as subarachnoid hemorrhage, ischemic stroke, and intracerebral hemorrhage.[21] [22] [23] This increase causes the coagulation system to become activated. Elevated D-dimer level is seen with coagulation disorder and is a poor prognostic factor. High D- dimer level is associated with severe grade of head injury.[19] [20]
Systemic activation of coagulation leads to widespread intravascular fibrin deposition and consumption of PLTs and coagulation factors. So, we found in our study that the PLT count and Fg level degraded, and thrombocytopenia and low Fg level could to be predictors of PHI.
An increased D-dimer level is associated with poor clinical outcome of subarachnoid hemorrhage, ischemic stroke, and trauma.[21] [22] [23] Moreover, D-dimer level shows plasmin activity not only in blood but also during tissue degradation and remodeling. In addition to aiding in the diagnosis of disseminated intravascular coagulation, it is also of clinical use when a suspicion of deep vein thrombosis or PE exists; it is promising as an exclusion test for PE if the results are negative, while positive results are quite nonspecific.[24] [25] Nevertheless, whether D-dimer levels correlate with the incidence of posttraumatic cerebral infarction, which often develops in patients with moderate or severe TBI, has not been previously reported[26]
Routine D-dimer laboratory testing is supposed to be a useful clinical test to evaluate the severity of head injury. Monitoring of D-dimer level may be helpful in estimating prognosis in patients who are hospitalized early after injury and who may develop PHI and may worsen there clinical condition. Sometimes, patients with mild head injury who are under observation may deteriorate neurologically. Therefore, the blood D-dimer level can provide useful prognostic marker for physicians concerning whether to transfer patients to a facilitated hospital.
Although we found D-dimer level to be associated with PHI, the mechanisms that explain the association between D-dimer and PHI are not understood fully. D-dimer, a marker of fibrin turnover, reflects an impaired coagulation and fibrinolysis pathways. In TBI patients, this abnormal function may lead to greater intracranial hematoma volume and early hemorrhagic growth, as we observed. However, D-dimer is one of the markers of hemostatic function which are acute-phase reactants. Hence, it is possible that elevated D-dimer levels in patients with progressing hemorrhage are simply a marker of a more severe lesion, as part of a reactant inflammatory process. In addition, a rise in plasma D-dimer concentration was independently associated to the incidence of posttraumatic PHI.[27] [28] D/F ratio, as opposed to plasma D-dimer concentrations and plasma Fg concentration, emerged as a predictive factor which is independent in the current investigation, indicating that it is more likely to predict the incidence of PHI.
The finding that severely ill patients had a higher D-dimer level is fascinating. Proinflammatory states in critically ill hospitalized patients had elevated D-dimer levels via cytokine activation of the coagulation cascade.[29] When the blood is clotting, thrombin and other intermediate products are produced. Some of these products, and in particular thrombin, can activate the inflammatory cascade.[30] D-dimer as an end product of both coagulation and fibrinolysis may trigger some detrimental actions directly. D-dimer itself may stimulate monocyte synthesis and release of proinflammatory cytokines such as interleukin-6,[31] which causes both development of edema and hematoma progression. Thus, activated inflammation and activated blood coagulation are possibly related and both contribute to the occurrence of PHI. Additionally, severe head-injured patients with high D-dimer concentration may be associated with organ failure resulting from microthrombosis. Liver failure induce the reduction of blood coagulation factor generation and further bleeding and hematoma progression may result.[32]
Two studies[15] (Sun et al 2011[33])probed the potential effect of D-dimer. The retrospective study of isolated TBI with extended coagulation profiling of 598 patients shows patients with international normalized ratio (INR) greater than 1.2 had presented more with shock and lower GCS score at the time of presentation and had PIH more frequently on repeat CT compared to INR less than 1.2.
Zhang et al meta-analysis of coagulation parameter and risk of PHI after TBI shows increased D-dimer with PHI in three studies and decreased Fg with PHI in three studies.
Our findings implied that abnormal D/F ratio might indicate occurrence of PHI, which might lead to focused monitoring among TBI patients, and thus save plenty of medical resources. Our interpretation form the basis for further studies exploring whether correcting these values would prevent PHI and moreover make for subsequent operation. However, there is no strong evidence that correcting laboratorial tests in this situation actually improves outcome.
The probability of PHI after TBI is highly associated with the GCS score, a traditional sign of a bad outcome following brain injury. Additionally, it is utilized to support clinical prediction of TBI.
#
Conclusion
We can conclude that D/F ratio can be used to predict the incidence of PHI within hours of TBI. Therefore, the patients with TBI who have a high D/F ratio should be further evaluated to rule out the possibility of PHI and prompt intervention can be initiated to avoid unwanted outcomes.
#
#
Conflict of Interest
None declared.
-
References
- 1 Kamal VK, Agrawal D, Pandey RM. Epidemiology, clinical characteristics and outcomes of traumatic brain injury: evidences from integrated level 1 trauma center in India. J Neurosci Rural Pract 2016; 7 (04) 515-525
- 2 Fleminger S, Ponsford J. Long term outcome after traumatic brain injury. BMJ 2005; 331 (7530): 1419-1420
- 3 Murray CJ, Lopez AD. Global Health Statistics: A Compendium of Incidence Prevalence and Mortality Estimates for over 200 Conditions. Cambridge, MA: Harvard University Press; 1996
- 4 Lopez AD, Murray CJ. The Global Burden of Disease: A Comprehensive Assessment of Mortality and Disability from Diseases, Injuries, and Risk Factors in 1990 and Projected to 2020. Cambridge, MA: Harvard University Press; 1996
- 5 Gururaj G. Epidemiology of traumatic brain injuries: Indian scenario. Neurol Res 2002; 24 (01) 24-28
- 6 Epstein DS, Mitra B, O'Reilly G, Rosenfeld JV, Cameron PA. Acute traumatic coagulopathy in the setting of isolated traumatic brain injury: a systematic review and meta-analysis. Injury 2014; 45 (05) 819-824
- 7 Van Beek JG, Mushkudiani NA, Steyerberg EW. et al. Prognostic value of admission laboratory parameters in traumatic brain injury: results from the IMPACT study. J Neurotrauma 2007; 24 (02) 315-328
- 8 Goldenberg NA, Jenkins S, Jack J. et al. Arteriopathy, D-dimer, and risk of poor neurologic outcome in childhood-onset arterial ischemic stroke. J Pediatr 2013; 162 (05) 1041-6.e1
- 9 Tian HL, Chen H, Wu BS. et al. D-dimer as a predictor of progressive hemorrhagic injury in patients with traumatic brain injury: analysis of 194 cases. Neurosurg Rev 2010; 33 (03) 359-365 , discussion 365–366
- 10 Yuan F, Ding J, Chen H. et al. Predicting progressive hemorrhagic injury after traumatic brain injury: derivation and validation of a risk score based on admission characteristics. J Neurotrauma 2012; 29 (12) 2137-2142
- 11 Juratli TA, Zang B, Litz RJ. et al. Early hemorrhagic progression of traumatic brain contusions: frequency, correlation with coagulation disorders, and patient outcome: a prospective study. J Neurotrauma 2014; 31 (17) 1521-1527
- 12 Wang K, Zhao DQ, Zhang JJ. et al. Risk factors of progressive brain contusion and relationship with outcome [in Chinese]. Zhejiang Da Xue Xue Bao Yi Xue Ban 2015; 44 (04) 410-416
- 13 Oertel M, Kelly DF, McArthur D. et al. Progressive hemorrhage after head trauma: predictors and consequences of the evolving injury. J Neurosurg 2002; 96 (01) 109-116
- 14 Stein SC, Spettell C, Young G, Ross SE. Delayed and progressive brain injury in closed-head trauma: radiological demonstration. Neurosurgery 1993; 32 (01) 25-30 , discussion 30–31
- 15 Tong WS, Zheng P, Zeng JS. et al. Prognosis analysis and risk factors related to progressive intracranial haemorrhage in patients with acute traumatic brain injury. Brain Inj 2012; 26 (09) 1136-1142
- 16 Wan X, Fan T, Wang S. et al. Progressive hemorrhagic injury in patients with traumatic intracerebral hemorrhage: characteristics, risk factors and impact on management. Acta Neurochir (Wien) 2017; 159 (02) 227-235
- 17 Allard CB, Scarpelini S, Rhind SG. et al. Abnormal coagulation tests are associated with progression of traumatic intracranial hemorrhage. J Trauma 2009; 67 (05) 959-967
- 18 Cepeda S, Gómez PA, Castaño-Leon AM, Martínez-Pérez R, Munarriz PM, Lagares A. Traumatic intracerebral hemorrhage: risk factors associated with progression. J Neurotrauma 2015; 32 (16) 1246-1253
- 19 Kuo JR, Lin KC, Lu CL, Lin HJ, Wang CC, Chang CH. Correlation of a high D-dimer level with poor outcome in traumatic intracranial hemorrhage. Eur J Neurol 2007; 14 (10) 1073-1078
- 20 Kuo JR, Chou TJ, Chio CC. Coagulopathy as a parameter to predict the outcome in head injury patients–analysis of 61 cases. J Clin Neurosci 2004; 11 (07) 710-714
- 21 Barber M, Langhorne P, Rumley A, Lowe GD, Stott DJ. Hemostatic function and progressing ischemic stroke: D-dimer predicts early clinical progression. Stroke 2004; 35 (06) 1421-1425
- 22 Delgado P, Alvarez-Sabín J, Abilleira S. et al. Plasma d-dimer predicts poor outcome after acute intracerebral hemorrhage. Neurology 2006; 67 (01) 94-98
- 23 Juvela S, Siironen J. D-dimer as an independent predictor for poor outcome after aneurysmal subarachnoid hemorrhage. Stroke 2006; 37 (06) 1451-1456
- 24 Rathbun SW, Whitsett TL, Vesely SK, Raskob GE. Clinical utility of D-dimer in patients with suspected pulmonary embolism and nondiagnostic lung scans or negative CT findings. Chest 2004; 125 (03) 851-855
- 25 Wells PS, Anderson DR, Rodger M. et al. Evaluation of D-dimer in the diagnosis of suspected deep-vein thrombosis. N Engl J Med 2003; 349 (13) 1227-1235
- 26 Tian HL, Geng Z, Cui YH. et al. Risk factors for posttraumatic cerebral infarction in patients with moderate or severe head trauma. Neurosurg Rev 2008; 31 (04) 431-436 , discussion 436–437
- 27 Zhang J, He M, Song Y, Xu J. Prognostic role of D-dimer level upon admission in patients with traumatic brain injury. Medicine (Baltimore) 2018; 97 (31) e11774
- 28 Yuan Q, Sun YR, Wu X. et al. Coagulopathy in traumatic brain injury and its correlation with progressive hemorrhagic injury: a systematic review and metaanalysis. J Neurotrauma 2016; 33 (14) 1279-1291
- 29 Williams MT, Aravindan N, Wallace MJ, Riedel BJ, Shaw AD. Venous thromboembolism in the intensive care unit. Crit Care Clin 2003; 19 (02) 185-207
- 30 Lee KR, Kawai N, Kim S, Sagher O, Hoff JT. Mechanisms of edema formation after intracerebral hemorrhage: effects of thrombin on cerebral blood flow, blood-brain barrier permeability, and cell survival in a rat model. J Neurosurg 1997; 86 (02) 272-278
- 31 Robson SC, Shephard EG, Kirsch RE. Fibrin degradation product D-dimer induces the synthesis and release of biologically active IL-1 beta, IL-6 and plasminogen activator inhibitors from monocytes in vitro. Br J Haematol 1994; 86 (02) 322-326
- 32 Levi M, Ten Cate H. Disseminated intravascular coagulation. N Engl J Med 1999; 341 (08) 586-592
- 33 Sun YR, Xi CH, Wang E. et al. Disseminated intravascular coagulation scores as predictors for progressive hemorrhage and neurological prognosis following traumatic brain injury. Neural Regen Res 2011; 6 (02) 136-141
Address for correspondence
Publication History
Article published online:
03 October 2024
© 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)
Thieme Medical and Scientific Publishers Pvt. Ltd.
A-12, 2nd Floor, Sector 2, Noida-201301 UP, India
-
References
- 1 Kamal VK, Agrawal D, Pandey RM. Epidemiology, clinical characteristics and outcomes of traumatic brain injury: evidences from integrated level 1 trauma center in India. J Neurosci Rural Pract 2016; 7 (04) 515-525
- 2 Fleminger S, Ponsford J. Long term outcome after traumatic brain injury. BMJ 2005; 331 (7530): 1419-1420
- 3 Murray CJ, Lopez AD. Global Health Statistics: A Compendium of Incidence Prevalence and Mortality Estimates for over 200 Conditions. Cambridge, MA: Harvard University Press; 1996
- 4 Lopez AD, Murray CJ. The Global Burden of Disease: A Comprehensive Assessment of Mortality and Disability from Diseases, Injuries, and Risk Factors in 1990 and Projected to 2020. Cambridge, MA: Harvard University Press; 1996
- 5 Gururaj G. Epidemiology of traumatic brain injuries: Indian scenario. Neurol Res 2002; 24 (01) 24-28
- 6 Epstein DS, Mitra B, O'Reilly G, Rosenfeld JV, Cameron PA. Acute traumatic coagulopathy in the setting of isolated traumatic brain injury: a systematic review and meta-analysis. Injury 2014; 45 (05) 819-824
- 7 Van Beek JG, Mushkudiani NA, Steyerberg EW. et al. Prognostic value of admission laboratory parameters in traumatic brain injury: results from the IMPACT study. J Neurotrauma 2007; 24 (02) 315-328
- 8 Goldenberg NA, Jenkins S, Jack J. et al. Arteriopathy, D-dimer, and risk of poor neurologic outcome in childhood-onset arterial ischemic stroke. J Pediatr 2013; 162 (05) 1041-6.e1
- 9 Tian HL, Chen H, Wu BS. et al. D-dimer as a predictor of progressive hemorrhagic injury in patients with traumatic brain injury: analysis of 194 cases. Neurosurg Rev 2010; 33 (03) 359-365 , discussion 365–366
- 10 Yuan F, Ding J, Chen H. et al. Predicting progressive hemorrhagic injury after traumatic brain injury: derivation and validation of a risk score based on admission characteristics. J Neurotrauma 2012; 29 (12) 2137-2142
- 11 Juratli TA, Zang B, Litz RJ. et al. Early hemorrhagic progression of traumatic brain contusions: frequency, correlation with coagulation disorders, and patient outcome: a prospective study. J Neurotrauma 2014; 31 (17) 1521-1527
- 12 Wang K, Zhao DQ, Zhang JJ. et al. Risk factors of progressive brain contusion and relationship with outcome [in Chinese]. Zhejiang Da Xue Xue Bao Yi Xue Ban 2015; 44 (04) 410-416
- 13 Oertel M, Kelly DF, McArthur D. et al. Progressive hemorrhage after head trauma: predictors and consequences of the evolving injury. J Neurosurg 2002; 96 (01) 109-116
- 14 Stein SC, Spettell C, Young G, Ross SE. Delayed and progressive brain injury in closed-head trauma: radiological demonstration. Neurosurgery 1993; 32 (01) 25-30 , discussion 30–31
- 15 Tong WS, Zheng P, Zeng JS. et al. Prognosis analysis and risk factors related to progressive intracranial haemorrhage in patients with acute traumatic brain injury. Brain Inj 2012; 26 (09) 1136-1142
- 16 Wan X, Fan T, Wang S. et al. Progressive hemorrhagic injury in patients with traumatic intracerebral hemorrhage: characteristics, risk factors and impact on management. Acta Neurochir (Wien) 2017; 159 (02) 227-235
- 17 Allard CB, Scarpelini S, Rhind SG. et al. Abnormal coagulation tests are associated with progression of traumatic intracranial hemorrhage. J Trauma 2009; 67 (05) 959-967
- 18 Cepeda S, Gómez PA, Castaño-Leon AM, Martínez-Pérez R, Munarriz PM, Lagares A. Traumatic intracerebral hemorrhage: risk factors associated with progression. J Neurotrauma 2015; 32 (16) 1246-1253
- 19 Kuo JR, Lin KC, Lu CL, Lin HJ, Wang CC, Chang CH. Correlation of a high D-dimer level with poor outcome in traumatic intracranial hemorrhage. Eur J Neurol 2007; 14 (10) 1073-1078
- 20 Kuo JR, Chou TJ, Chio CC. Coagulopathy as a parameter to predict the outcome in head injury patients–analysis of 61 cases. J Clin Neurosci 2004; 11 (07) 710-714
- 21 Barber M, Langhorne P, Rumley A, Lowe GD, Stott DJ. Hemostatic function and progressing ischemic stroke: D-dimer predicts early clinical progression. Stroke 2004; 35 (06) 1421-1425
- 22 Delgado P, Alvarez-Sabín J, Abilleira S. et al. Plasma d-dimer predicts poor outcome after acute intracerebral hemorrhage. Neurology 2006; 67 (01) 94-98
- 23 Juvela S, Siironen J. D-dimer as an independent predictor for poor outcome after aneurysmal subarachnoid hemorrhage. Stroke 2006; 37 (06) 1451-1456
- 24 Rathbun SW, Whitsett TL, Vesely SK, Raskob GE. Clinical utility of D-dimer in patients with suspected pulmonary embolism and nondiagnostic lung scans or negative CT findings. Chest 2004; 125 (03) 851-855
- 25 Wells PS, Anderson DR, Rodger M. et al. Evaluation of D-dimer in the diagnosis of suspected deep-vein thrombosis. N Engl J Med 2003; 349 (13) 1227-1235
- 26 Tian HL, Geng Z, Cui YH. et al. Risk factors for posttraumatic cerebral infarction in patients with moderate or severe head trauma. Neurosurg Rev 2008; 31 (04) 431-436 , discussion 436–437
- 27 Zhang J, He M, Song Y, Xu J. Prognostic role of D-dimer level upon admission in patients with traumatic brain injury. Medicine (Baltimore) 2018; 97 (31) e11774
- 28 Yuan Q, Sun YR, Wu X. et al. Coagulopathy in traumatic brain injury and its correlation with progressive hemorrhagic injury: a systematic review and metaanalysis. J Neurotrauma 2016; 33 (14) 1279-1291
- 29 Williams MT, Aravindan N, Wallace MJ, Riedel BJ, Shaw AD. Venous thromboembolism in the intensive care unit. Crit Care Clin 2003; 19 (02) 185-207
- 30 Lee KR, Kawai N, Kim S, Sagher O, Hoff JT. Mechanisms of edema formation after intracerebral hemorrhage: effects of thrombin on cerebral blood flow, blood-brain barrier permeability, and cell survival in a rat model. J Neurosurg 1997; 86 (02) 272-278
- 31 Robson SC, Shephard EG, Kirsch RE. Fibrin degradation product D-dimer induces the synthesis and release of biologically active IL-1 beta, IL-6 and plasminogen activator inhibitors from monocytes in vitro. Br J Haematol 1994; 86 (02) 322-326
- 32 Levi M, Ten Cate H. Disseminated intravascular coagulation. N Engl J Med 1999; 341 (08) 586-592
- 33 Sun YR, Xi CH, Wang E. et al. Disseminated intravascular coagulation scores as predictors for progressive hemorrhage and neurological prognosis following traumatic brain injury. Neural Regen Res 2011; 6 (02) 136-141