scholarly journals Extended Coagulation Profiling in Isolated Traumatic Brain Injury: A CENTER-TBI Analysis

2021 ◽  
Author(s):  
Julia K. Böhm ◽  
Victoria Schaeben ◽  
Nadine Schäfer ◽  
Helge Güting ◽  
Rolf Lefering ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Protein C ◽  
Thrombin Generation ◽  
Laboratory Data ◽  
Thrombin Time ◽  
Coagulation Assays ◽  
Depth Analysis ◽  
Fibrin Monomers ◽  
D Dimer

Abstract Background Trauma-induced coagulopathy in traumatic brain injury (TBI) remains associated with high rates of complications, unfavorable outcomes, and mortality. The underlying mechanisms are largely unknown. Embedded in the prospective multinational Collaborative European Neurotrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study, coagulation profiles beyond standard conventional coagulation assays were assessed in patients with isolated TBI within the very early hours of injury. Methods Results from blood samples (citrate/EDTA) obtained on hospital admission were matched with clinical and routine laboratory data of patients with TBI captured in the CENTER-TBI central database. To minimize confounding factors, patients with strictly isolated TBI (iTBI) (n = 88) were selected and stratified for coagulopathy by routine international normalized ratio (INR): (1) INR < 1.2 and (2) INR ≥ 1.2. An INR > 1.2 has been well adopted over time as a threshold to define trauma-related coagulopathy in general trauma populations. The following parameters were evaluated: quick’s value, activated partial thromboplastin time, fibrinogen, thrombin time, antithrombin, coagulation factor activity of factors V, VIII, IX, and XIII, protein C and S, plasminogen, D-dimer, fibrinolysis-regulating parameters (thrombin activatable fibrinolysis inhibitor, plasminogen activator inhibitor 1, antiplasmin), thrombin generation, and fibrin monomers. Results Patients with iTBI with INR ≥ 1.2 (n = 16) had a high incidence of progressive intracranial hemorrhage associated with increased mortality and unfavorable outcome compared with patients with INR < 1.2 (n = 72). Activity of coagulation factors V, VIII, IX, and XIII dropped on average by 15–20% between the groups whereas protein C and S levels dropped by 20%. With an elevated INR, thrombin generation decreased, as reflected by lower peak height and endogenous thrombin potential (ETP), whereas the amount of fibrin monomers increased. Plasminogen activity significantly decreased from 89% in patients with INR < 1.2 to 76% in patients with INR ≥ 1.2. Moreover, D-dimer levels significantly increased from a mean of 943 mg/L in patients with INR < 1.2 to 1,301 mg/L in patients with INR ≥ 1.2. Conclusions This more in-depth analysis beyond routine conventional coagulation assays suggests a counterbalanced regulation of coagulation and fibrinolysis in patients with iTBI with hemostatic abnormalities. We observed distinct patterns involving key pathways of the highly complex and dynamic coagulation system that offer windows of opportunity for further research. Whether the changes observed on factor levels may be relevant and explain the worse outcome or the more severe brain injuries by themselves remains speculative.

scholarly journals Prospective Analysis of Coagulopathy Associated with Isolated Traumatic Brain Injury and Clinical Outcome

2021 ◽  
Author(s):  
Gopal Krishna ◽  
Varun Aggarwal ◽  
Ishwar Singh
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Head Injury ◽  
Clinical Outcome ◽  
Road Traffic ◽  
Statistical Significance ◽  
Platelet Counts ◽  
Coagulation Abnormalities ◽  
The Mean ◽  
D Dimer

Abstract Introduction Traumatic brain injury (TBI) affects the coagulation pathway in a distinct way than does extracranial trauma. The extent of coagulation abnormalities varies from bleeding diathesis to disseminated thrombosis. Design Prospective study. Methods The study included 50 patients of isolated TBI with cohorts of moderate (MHI) and severe head injury (SHI). Coagulopathy was graded according to the values of parameters in single laboratory. The incidence of coagulopathy according to the severity of TBI and correlation with disseminated intravascular coagulation (DIC) score, platelets, prothrombin time (PT), activated partial thromboplastin time (APTT), D-dimer, and fibrinogen was observed. The comparison was also made between expired and discharged patients within each group. It also compared coagulation derailments with clinical presentation (Glasgow Coma Scale [GCS]) and outcome (Glasgow Outcome Scale [GOS]). Results Road traffic accident was the primary (72%) mode of injury. Fifty-two percent had MHI and rest had SHI. Eighty-four percent of cases were managed conservatively. The mean GCS was 12.23 and 5.75 in MHI and SHI, respectively. Sixty-two percent of MHI and 96% of the patients with SHI had coagulation abnormalities. On statistical analysis, DIC score (p < 0.001) strongly correlated with the severity of head injury and GOS. PT and APTT were also significantly associated with the severity of TBI. In patients with moderate TBI, D-dimer and platelet counts showed association with clinical outcome. Fibrinogen levels did not show any statistical significance. The mean platelet counts remained normal in both the groups of TBI. The mean GOS was 1.54 and 4.62 in SHI and MHI, respectively. Conclusion Coagulopathy is common in isolated TBI. The basic laboratory parameters are reliable predictors of coagulation abnormalities in TBI. Coagulopathy is directly associated with the severity of TBI, GCS, and poor outcome.

scholarly journals Correlation of D-Dimer level with outcome in traumatic brain injury

2016 ◽  
Vol 17 (1) ◽  
pp. 21-30
Author(s):  
Pradip Prasad Subedi ◽  
Sushil Krishna Shilpakar
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Hospital Stay ◽  
Glasgow Outcome Scale ◽  
Significant Proportion ◽  
Duration Of Hospital Stay ◽  
Icu Stay ◽  
The Mean ◽  
Hospital Stay Duration ◽  
D Dimer

Introduction: Traumatic brain injury (TBI) is a common neurosurgical emergency and a common public health problem with high mortality and long term morbidity. The cost incurred by TBI is immense. The major determinant of outcome following TBI is the severity of the primary injury. However, secondary injuries including coagulopathy are treatable prognostic factors. Many studies have revealed that coagulopathy of trauma depicted by increasing level of D-dimer is associated with poor prognosis in TBI. So, early dectection and correction of such abnormality is very important in management of TBI.Methods: This is a prospective observational study conducted at Department of Surgery TUTH (Tribhuvan University Teaching Hospital), Kathmandu,Nepal over a period of one year. One hundred and forty eight patients of TBI were included in the study. Clinical profile of the patients and D-dimer level were monitored during the hospital course. D-dimer level was correlated with outcome variables including duration of hospital stay, duration of Intensive care unit (ICU) stay and Glasgow outcome scale (GOS).Results: A total of 194 patients were admitted with the diagnosis of traumatic brain injury during the study period and out of them 148 patients were enrolled for the study. Out of 148 patients one hundred and twenty (81.1%) were males and twenty eight (18.9%) were females. The mean age was 29.71±18.07 and the age ranged from 1 to 78 years. Seventy (47.3%) patient were between 21 to 40 years of age. The mean duration of hospital stay was 9.83±13.58 days and the mean duration of ICU stay was 3.78±7.06 days. Contusion was the most common lesion in our patients. Of the patients studied 111 patients (75%)  had good recovery with GOS of 5, 9  patients (6.1%)  had GOS of 4, 6 patients (4.1%)  had GOS of 3, 1 patients (0.7%)  had GOS of 2 and 21 patients (14.1%)  had GOS of 1. Normal D-dimer was seen in 102 patients (68.9%) and elevated D-dimer in 46 patients (31.1%). Man –Whitney test shows higher D-dimer levels positively correlated with duration of hospital stay, duration of ICU stay and Glasgow Outcome Scale. Pearson chi-square test revealed higher levels of D-dimer correlated with grade of injury but not with mode of injury.Conclusion: D-dimer is elevated in significant proportion of patients with TBI and abnormal D-dimer level is associated with poor outcome in TBI.Journal of Society of Surgeons of Nepal Vol.17(1) 2014: 21-30

scholarly journals Age-Related Differences in the Time Course of Coagulation and Fibrinolytic Parameters in Patients with Traumatic Brain Injury

2020 ◽  
Vol 21 (16) ◽  
pp. 5613
Author(s):  
Ryuta Nakae ◽  
Yu Fujiki ◽  
Yasuhiro Takayama ◽  
Takahiro Kanaya ◽  
Yutaka Igarashi ◽  
...  
Keyword(s):  
Risk Factors ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Propensity Score ◽  
Older Patients ◽  
Multivariate Logistic Regression Analysis ◽  
The Elderly ◽  
Elderly Group ◽  
Post Injury ◽  
D Dimer

Coagulopathy and older age are common and well-recognized risk factors for poorer outcomes in traumatic brain injury (TBI) patients; however, the relationships between coagulopathy and age remain unclear. We hypothesized that coagulation/fibrinolytic abnormalities are more pronounced in older patients and may be a factor in poorer outcomes. We retrospectively evaluated severe TBI cases in which fibrinogen and D-dimer were measured on arrival and 3–6 h after injury. Propensity score-matched analyses were performed to adjust baseline characteristics between older patients (the “elderly group,” aged ≥75 y) and younger patients (the “non-elderly group,” aged 16–74 y). A total of 1294 cases (elderly group: 395, non-elderly group: 899) were assessed, and propensity score matching created a matched cohort of 324 pairs. Fibrinogen on admission, the degree of reduction in fibrinogen between admission and 3–6 h post-injury, and D-dimer levels between admission and 3–6 h post-injury were significantly more abnormal in the elderly group than in the non-elderly group. On multivariate logistic regression analysis, independent risk factors for poor prognosis included low fibrinogen and high D-dimer levels on admission. Posttraumatic coagulation and fibrinolytic abnormalities are more severe in older patients, and fibrinogen and D-dimer abnormalities are negative predictive factors.

scholarly journals Probability of Soluble Tissue Factor Release Lead to the Elevation of D-dimer as a Biomarker for Traumatic Brain Injury

2019 ◽  
Vol 59 (2) ◽  
pp. 63-67 ◽  
Author(s):  
Eiichi SUEHIRO ◽  
Yuichi FUJIYAMA ◽  
Miwa KIYOHIRA ◽  
Yukari MOTOKI ◽  
Junzo NOJIMA ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Tissue Factor ◽  
D Dimer ◽  
Factor Release

scholarly journals Translational Insights into Traumatic Brain Injury Occurring during Dabigatran or Warfarin Anticoagulation

2014 ◽  
Vol 34 (5) ◽  
pp. 870-875 ◽  
Author(s):  
Jan Hendrik Schaefer ◽  
Wendy Leung ◽  
Limin Wu ◽  
Elizabeth M Van Cott ◽  
Josephine Lok ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Intracerebral Hemorrhage ◽  
Oral Anticoagulants ◽  
International Normalized Ratio ◽  
Thrombin Time ◽  
Limited Data ◽  
Hemorrhage Volume ◽  
Post Hoc ◽  
Safety Advantage

To date, only limited data are available on the effects of pretreatment with novel oral anticoagulants in the event of traumatic brain injury (TBI). We determined intracerebral hemorrhage volume and functional outcome in a standardized TBI model in mice treated with warfarin or dabigatran. Additionally, we investigated whether excess concentrations of dabigatran could increase bleeding and whether this was preventable by using prothrombin complex concentrate (PCC). C57 mice were treated orally with warfarin or dabigatran; sham-treated mice served as controls. Effective anticoagulation was verified by measurement of international normalized ratio and diluted thrombin time, and TBI was induced by controlled cortical impact (CCI). Twenty-four hours after CCI, intracerebral hemorrhage volume was larger in warfarin-pretreated mice than in controls (10.1 ± 4.9 vs 4.1 ± 1.7 μL; analysis of variance post hoc P = 0.001), but no difference was found between controls and dabigatran-pretreated mice (5.3 ± 1.5 μL). PCC applied 30 minutes after CCI did not reliably reduce intracerebral hemorrhage induced by excess dabigatran concentration compared with saline (10.4 ± 11.2 vs 8.7 ± 7.1 μL). Our data suggest pathophysiological differences in TBI occurring during warfarin and dabigatran anticoagulation. The reduced hemorrhage formation under dabigatran therapy could present a safety advantage compared with warfarin. An excess dabigatran concentration, however, can increase hemorrhage.

scholarly journals Diagnostic Accuracy in Acute Venous Thromboembolism: Comparing D-Dimer, Thrombin Generation, Overall Hemostatic Potential, and Fibrin Monomers

TH Open ◽  
2020 ◽  
Vol 04 (03) ◽  
pp. e178-e188
Author(s):  
Maria Farm ◽  
Aleksandra Antovic ◽  
David E. Schmidt ◽  
Niklas Bark ◽  
Nida Soutari ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Venous Thrombosis ◽  
Thrombin Generation ◽  
Medical Emergency ◽  
Diagnostic Study ◽  
Healthy Controls ◽  
Clinical Biomarkers ◽  
Acute Venous Thromboembolism ◽  
Fibrin Monomers ◽  
D Dimer

Abstract Introduction For acute venous thromboembolism (VTE), a biomarker with higher specificity than D-dimer would be of great clinical use. Thrombin generation and overall hemostatic potential (OHP) reflect the hemostatic balance by globally assessing multiple coagulation factors and inhibitors. These tests discriminate between healthy controls and patients with a prothrombotic tendency but have yet to be established as clinical biomarkers of VTE. Objective This study compares endogenous thrombin potential (ETP) and OHP to D-dimer and fibrin monomers (FM) in outpatients with suspected VTE. Methods A cross-sectional diagnostic study where 954 patients with suspected pulmonary embolism or deep venous thrombosis were recruited consecutively from the medical emergency department at Karolinska University Hospital. D-dimer, FM, OHP, and ETP were analyzed in a subpopulation of 60 patients with VTE and 98 matched controls without VTE. VTE was verified either by ultrasonography or computed tomography and clinical data were collected from medical records. Results Compared with healthy controls, both VTE and non-VTE patients displayed prothrombotic profiles in OHP and ETP. D-dimer, FM, ETP area under the curve (AUC), and ETP Tlag were significantly different between patients with VTE and non-VTE. The largest receiver-operating characteristic AUCs for discrimination between VTE and non-VTE, were found in D-dimer with 0.94, FM 0.77, and ETP AUC 0.65. No useful cutoff could be identified for the ETP or the OHP assay. Conclusion Compared with D-dimer, neither ETP nor OHP were clinically viable biomarkers of acute venous thrombosis. The data indicated that a large portion of the emergency patients with suspected VTE were in a prothrombotic state.

Plasma hemostasis in patients with coronavirus infection caused by SARS-CoV-2.

2020 ◽  
Author(s):  
О.Ю. Матвиенко ◽  
Н.Е. Корсакова ◽  
А.А. Лернер ◽  
Т.Н. Шведова ◽  
Л.П. Папаян
Keyword(s):  
Von Willebrand Factor ◽  
Protein C ◽  
Thrombin Generation ◽  
Disease Course ◽  
Anticoagulant Treatment ◽  
Coronavirus Infection ◽  
High Level ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
D Dimer

Введение. Пандемия COVID-19 стала глобальной проблемой мирового сообщества. Основным патогенетическим механизмом заболевания представляется развитие иммунного тромбоза, результатом которого являются нарушение микроциркуляции, артериальные и венозные тромбозы, респираторный дистресс-синдром, полиорганная недостаточность. Изучение механизмов развития гиперкоагуляционных изменений у пациентов с COVID-19 вызывает огромный интерес и позволит улучшить исходы заболевания. Цель исследования: оценка состояния плазменного звена гемостаза у пациентов с коронавирусной инфекцией в остром периоде заболевания. Материалы и методы. Обследованы 59 пациентов с тяжелым и среднетяжелым течением коронавирусной инфекции, получавшие антикоагулянтную профилактику. Определяли следующие параметры системы гемостаза: активированное парциальное тромбопластиновое время, протромбиновый тест, концентрацию фибриногена, активность фактора VIII, антитромбина, протеинов C и S, содержание D-димера, фактора Виллебранда и гомоцистеина, а также генерацию тромбина методом калиброванной автоматизированной тромбинографии. Результаты. У пациентов с COVID-19 по сравнению со здоровыми лицами было выявлено увеличение концентрации фибриногена, уровня фактора Виллебранда, гомоцистеина и D-димера, значительное снижение уровня свободного протеина S, усиление генерации тромбина, снижение чувствительности к тромбомодулину. Была выявлена прямая корреляция между тяжестью состояния пациентов и уровнями фактора Виллебранда и гомоцистеина. Заключение. Несмотря на проводимую антикоагулянтную терапию, у пациентов с коронавирусной инфекцией отмечены выраженные признаки активации системы гемостаза, которые характеризуются как повышением отдельных маркеров гиперкоагуляции, так и значимым усилением генерации тромбина на фоне угнетения работы системы протеина С. Повышенный уровень гомоцистеина плазмы крови является дополнительным фактором риска, ухудшающим течение заболевания. Значительное повышение уровня фактора Виллебранда может быть неблагоприятным прогностическим признаком течения заболевания. Background. The COVID-19 pandemic is a global health care challenge. The concept of immunothrombosis has established as a central pathogenic factor leading to thrombosis complications, respiratory insufficiency and multiple organ failure. The study of hypercoagulability mechanisms in patients with COVID-19 may be useful for improving disease’s outcomes. Objectives: to evaluate plasma hemostasis in patients with coronavirus infection at the acute period of the disease. Patients / Methods. We examined 59 patients with severe and moderate coronavirus infection who received anticoagulant treatment. The following hemostasis parameters were determined: activated partial thromboplastin time, prothrombin test, fibrinogen, factor VIII, von Willebrand factor, D-dimer, protein C and S, homocysteine, and thrombin generation. Results. Fibrinogen, von Willebrand factor, D-dimer, homocysteine, and thrombin generation were higher in patients with COVID-19 than in healthy people, protein S was reduced. The direct correlation between the severity of the patient’s condition and the levels of von Willebrand factor and homocysteine was found. Conclusions. Patients with COVID-19 had significant hypercoagulability despite of the anticoagulant treatment. Signs of hemostasis activation are characterized by both increasing of hypercoagulation individual markers and thrombin generation with inhibition of protein C system. High level of plasma homocysteine is an additional risk factor that worsens the disease course. High level of von Willebrand factor may be an unfavorable prognostic sign of the disease course.

scholarly journals Serum D-Dimer Concentrations Are Increased after Pediatric Traumatic Brain Injury

2015 ◽  
Vol 166 (2) ◽  
pp. 383-388 ◽  
Author(s):  
Rachel P. Berger ◽  
Janet Fromkin ◽  
Pam Rubin ◽  
John Snyder ◽  
Rudolph Richichi ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Pediatric Traumatic Brain Injury ◽  
D Dimer
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