Thromboelastometry-identified Haemostatic Changes in Isolated Traumatic Brain Injury

Study Overview
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Brief Summary
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A prospective open-label case-control study will be performed aiming to assess the utility of thromboelastometry (ROTEM) for identification of hemostatic changes, goal-directed coagulation management, and prognosis of intracranial hemorrhagic injury progression as well as clinical outcome in patients with isolated traumatic brain injury. Patients undergoing craniotomy to treat traumatic brain injury will be enrolled. All patients will undergo standard perioperative coagulation analysis (APTT, PT, INR, fibrinogen levels, platelet count), whereas ROTEM-guided group will additionally be tested with ROTEM. Cases will be managed according to a ROTEM-based algorithm, and Controls will be treated as usual (based on clinical judging). Comparative analysis of acquired demographic, clinical and laboratory data will be performed. The investigators believe that ROTEM results could provide better insight into perioperative coagulation changes, be beneficial to patient blood management, and result in better outcome.

Detailed Description
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Aim of the study: To assess the utility of thromboelastometry for identification of hemostatic changes, goal-directed coagulation management, and prognosis of intracranial hemorrhagic injury progression as well as clinical outcome in patients with isolated traumatic brain injury. Objectives: To evaluate perioperative prevalence and characteristics of thromboelastometry identified coagulopathy in neurosurgical patients with isolated traumatic brain injury; To assess the correlation between routine laboratory test results and thromboelastometric findings; To evaluate the influence of thromboelastometric findings and goal-directed coagulation management on the progression of intracranial hemorrhagic injury; To evaluate the utility of thromboelastometry for goal-directed coagulation management, and its possible influence on clinical outcome. Study background: Traumatic brain injury still accounts for a considerable proportion of preventable deaths worldwide. The prevalence of coagulation derangements among patients with traumatic brain injury (TBI) is high and approximates 30 % (1,2). The main hypothesis explaining the development of coagulopathy in the absence of massive bleeding is extensive release of tissue factor from the damaged brain tissue and subsequent over-activation of coagulation leading to consumption of coagulation substrates. The presence of coagulopathy in the setting of TBI is associated with high risk of intracranial hemorrhagic insult progression and death (3,4). Many authors investigating coagulopathy associated with traumatic brain injury have used routine coagulation tests, such as APTT, PT, INR, fibrinogen levels. However, those tests do not reflect the overall clot quality and reflect only separate parts of the coagulation process. Craniotomy for traumatic brain injury is an urgent high-risk procedure presenting a serious challenge for the anesthesiology team. Significant, diffuse bleeding is not infrequent, and the spectrum of neurosurgical hemostatic options is limited. Moreover, even small amounts of intracranial blood may be life-threatening. Therefore the maintenance of optimal physiologic clotting capacity is crucial. Literature data investigating the use of ROTEM in TBI patients is still limited (5,6). The investigators believe that thromboelastometry could provide novel insights into the dynamic coagulation changes of TBI patients. Moreover, it could serve as a clinical tool for targeted coagulation management in the perioperative period of patients undergoing craniotomies for intracranial traumatic hematomas, and prove beneficial for patient outcome. Materials and methods: A prospective open-label case-control study will be performed. Adult isolated traumatic brain injury patients undergoing craniotomy and will be enrolled. Required sample size was calculated based on the average number of craniotomies performed to treat traumatic brain injury during the past five years in a tertiary neurosurgical centre. The investigators plan to enroll 70 patients into the ROTEM-guided group (Cases), and 70 patients into the conventional therapy group (Controls). All patients will undergo standard coagulation analysis (APTT, PT, INR, fibrinogen levels, platelet count) preoperatively, and 3 days postoperatively, whereas ROTEM-guided group patients will additionally be tested with ROTEM (EXTEM, INTEM, FIBTEM, APTEM). Coagulation management decisions in the ROTEM-guided group will be made according to a ROTEM-based algorithm for goal-directed hemostatic therapy. Conventional therapy group will be treated as usual. Perioperative demographic, clinical and laboratory data of study patients will be registered. Early neurological state (on postoperative days 1,2,3,7, and until discharge) will be assessed according to the Glasgow coma scale. Late neurological outcome (6 and 12 months postoperatively) will be assessed according to Glasgow outcome scale. Comparative analysis of Case and Control groups will be performed. Perioperative prevalence and characteristics of coagulopathy in neurosurgical patients with isolated traumatic brain injury will be estimated. Correlation between routine laboratory test results and thromboelastometric findings will be assessed. The influence of thromboelastometric findings and goal-directed coagulation management on the progression of intracranial hemorrhagic injury will be assessed. The influence of goal-directed coagulation management on clinical outcome will be evaluated. Anticipated scientific and clinical benefits: The investigators believe that ROTEM results could provide better insight into perioperative coagulation changes, be beneficial to patient blood management, and result in better outcome.

Official Title
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The Influence of Thromboelastometry-identified Haemostatic Changes on Haemorrhagic Progression of Intracranial Injury and Clinical Outcome in Patients With Isolated Traumatic Brain Injury

Conditions
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Coagulation Disorder, Brain Injuries, Traumatic, Bleeding

Intervention / Treatment
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* Other: Thromboelastometry-guided haemostatic treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Isolated traumatic brain injury (within 48 hours) (AIS head >= 3) Urgent craniotomy is necessary A written informed consent is acquired from the patient or his/her representative Exclusion Criteria: Refusal / inability to acquire an informed consent Significant trauma to other body regions (AIS other regions >= 3) Data on significant chronic hepatic or hematologic illness Use of oral anticoagulants or antiplatelet agents Pregnancy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A case-control study. Conventional management patients are considered as controls whereas goal-directed management patients will be considered cases.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Conventional therapy<br>Intraoperative haemostatic treatment is based on conventional coagulation assays. | |
| Active Comparator: Goal-directed therapy<br>Thromboelastometry-guided haemostatic treatment is provided intraoperatively. | Other: Thromboelastometry-guided haemostatic treatment<br>* Administration of blood products and/or procoagulants is based on thromboelastometric assays.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality | Mortality of patients in both groups | 30 days | 
| Early neurological state according to Glasgow coma scale | Glasgow coma scale (GCS) is used to objectively assess the level of consciousness after neurological injury according to best eye (range 1 to 4), verbal (range 1 to 5) and motor (range 1 to 6) response of the patient. Eye, verbal and motor scores are summed to give the total Glasgow coma score (range 3 to 15). The lowest possible GCS (the sum) is 3 (deep coma or death), while the highest is 15 (fully awake person). | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Coagulation abnormalities on conventional coagulation assays and ROTEM | The number of patients with abnormal results of PT (prothrombin time), INR (international normalized ratio), APTT (activated partial thromboplastin time), fibrinogen concentration, platelet count and/or any abnormal thromboelastometric (ROTEM) parameter | 72 hours | 
| Progressive hemorrhagic injury | Evidence of new or increased intracranial hemorrhagic injury | 30 days | 
| Clinical outcome according to Glasgow outcome score | The Glasgow Outcome Score (GOS) is used to divide patients with traumatic brain injury into groups (range 1 to 5) that allow standardised descriptions of the objective degree of recovery as follows: Death Persistent vegetative state - Severe damage with prolonged state of unresponsiveness and a lack of higher mental functions Severe disability - Severe injury with permanent need for help with daily living Moderate disability - No need for assistance in everyday life, employment is possible but may require special equipment Low disability - Light damage with minor neurological and psychological deficits | Up to 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Traumatic brain injury, Craniotomy, Goal-directed treatment, Thromboelastometry