warfarin and Brain-Injuries

Venous thromboembolism is a life-threatening complication of traumatic brain injury. Consequently, knowledge of available screening, diagnostic, prophylactic, and treatment methods is critical to the management of the individual with traumatic brain injury. Venous thromboembolic risk varies among individuals, resulting in unique screening and prophylactic needs for each patient. In addition, anticoagulation, commonly employed for prophylaxis and treatment in other patient populations, may create an increased risk for intracranial hemorrhage when utilized following traumatic brain injury. The cost, sensitivity, specificity, efficacy, potential side effects, and alternatives for preventing, detecting, and treating venous thromboembolism are important considerations discussed in this article.

Topics: Acute Disease; Anticoagulants; Bandages; Brain Injuries; Heparin; Humans; Thromboembolism; Vena Cava Filters; Venous Thrombosis; Warfarin

Deep-venous thrombosis (DVT) of the lower extremity occurs frequently in a variety of patients, including those with traumatic brain injury (TBI), during their rehabilitation. Thrombosis of the major veins of the upper extremity is believed to be relatively rare, although it has increased in recent years due to the routine use of indwelling percutaneous central venous catheters. Upper extremity pain and swelling in a TBI patient is commonly attributed to heterotopic ossification, reflex sympathetic dystrophy, or occult fracture. Clinicians may not consider DVT in the differential diagnosis. No longer regarded as a benign disorder, we report the successful outcome in a 27-year-old with TBI who developed an upper extremity DVT after subclavian catheterization. The diagnostic findings, as well as treatment recommendations are reviewed.

Topics: Adult; Axillary Vein; Brain Injuries; Catheterization, Peripheral; Catheters, Indwelling; Heparin; Humans; Male; Subclavian Vein; Thrombosis; Warfarin

Brain injury from stroke and traumatic brain injury (TBI) may result in a persistent neuroinflammatory response in the injury penumbra. This response may include microglial activation and excess levels of tumour necrosis factor (TNF). Previous experimental data suggest that etanercept, a selective TNF inhibitor, has the ability to ameliorate microglial activation and modulate the adverse synaptic effects of excess TNF. Perispinal administration may enhance etanercept delivery across the blood-CSF barrier.. The objective of this study was to systematically examine the clinical response following perispinal administration of etanercept in a cohort of patients with chronic neurological dysfunction after stroke and TBI.. After approval by an independent external institutional review board (IRB), a chart review of all patients with chronic neurological dysfunction following stroke or TBI who were treated open-label with perispinal etanercept (PSE) from November 1, 2010 to July 14, 2012 at a group medical practice was performed.. The treated cohort included 629 consecutive patients. Charts of 617 patients following stroke and 12 patients following TBI were reviewed. The mean age of the stroke patients was 65.8 years ± 13.15 (range 13-97). The mean interval between treatment with PSE and stroke was 42.0 ± 57.84 months (range 0.5-419); for TBI the mean interval was 115.2 ± 160.22 months (range 4-537). Statistically significant improvements in motor impairment, spasticity, sensory impairment, cognition, psychological/behavioural function, aphasia and pain were noted in the stroke group, with a wide variety of additional clinical improvements noted in individuals, such as reductions in pseudobulbar affect and urinary incontinence. Improvements in multiple domains were typical. Significant improvement was noted irrespective of the length of time before treatment was initiated; there was evidence of a strong treatment effect even in the subgroup of patients treated more than 10 years after stroke and TBI. In the TBI cohort, motor impairment and spasticity were statistically significantly reduced.. Irrespective of the methodological limitations, the present results provide clinical evidence that stroke and TBI may lead to a persistent and ongoing neuroinflammatory response in the brain that is amenable to therapeutic intervention by selective inhibition of TNF, even years after the acute injury.. Excess TNF contributes to chronic neurological, neuropsychiatric and clinical impairment after stroke and TBI. Perispinal administration of etanercept produces clinical improvement in patients with chronic neurological dysfunction following stroke and TBI. The therapeutic window extends beyond a decade after stroke and TBI. Randomized clinical trials will be necessary to further quantify and characterize the clinical response.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Brain Injuries; Cohort Studies; Etanercept; Female; Humans; Immunoglobulin G; Injections, Spinal; Male; Middle Aged; Motor Skills; Muscle Spasticity; Nervous System Diseases; Pain Management; Receptors, Tumor Necrosis Factor; Recovery of Function; Sensation; Stroke; Treatment Outcome; Tumor Necrosis Factor-alpha; Walking; Warfarin; Young Adult

We determine the prevalence of significant intracranial injury among adults with blunt head trauma who are receiving preinjury anticoagulant or antiplatelet medications.. This was a multicenter, prospective, observational study conducted from December 2007 to December 2015. Patients were enrolled in 3 emergency departments (EDs) in the United States. Adults with blunt head trauma who underwent neuroimaging in the ED were included. Use of preinjury aspirin, clopidogrel, and warfarin was recorded. Data on direct oral anticoagulants were not specifically recorded. The primary outcome was prevalence of significant intracranial injury on neuroimaging. The secondary outcome was receipt of neurosurgical intervention.. Among 9,070 patients enrolled in this study, the median age was 53.8 years (interquartile range 34.7 to 74.3 years) and 60.7% were men. A total of 1,323 patients (14.6%) were receiving antiplatelet medications or warfarin, including 635 receiving aspirin alone, 109 clopidogrel alone, and 406 warfarin alone. Compared with that of patients without any coagulopathy, the relative risk of significant intracranial injury was 1.29 (95% confidence interval [CI] 0.88 to 1.87) for patients receiving aspirin alone, 0.75 (95% CI 0.24 to 2.30) for those receiving clopidogrel alone, and 1.88 (95% CI 1.28 to 2.75) for those receiving warfarin alone. The relative risk of significant intracranial injury was 2.88 (95% CI 1.53 to 5.42) for patients receiving aspirin and clopidogrel in combination.. Patients receiving preinjury warfarin or a combination of aspirin and clopidogrel were at increased risk for significant intracranial injury, but not those receiving aspirin alone. Clinicians should have a low threshold for neuroimaging when evaluating patients receiving warfarin or a combination of aspirin and clopidogrel.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Aspirin; Brain Injuries; Clopidogrel; Female; Head Injuries, Closed; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Prevalence; Prospective Studies; Risk Factors; Warfarin

This study examined warfarin usage for elderly Medicare beneficiaries with atrial fibrillation (AF) who suffered traumatic brain injury (TBI), hip fracture, or torso injuries. Using the 5% Chronic Condition Data Warehouse administrative claims data, this study included fee-for-service Medicare beneficiaries who had a single injury hospitalization (TBI, hip fracture, or major torso injury) between 1/1/2007 and 12/31/2009, with complete Medicare Parts A, B (no Medicare Advantage), and D coverage 6 months before injury, and who were aged 66 years or older and diagnosed with AF at least 1 year before injury. About 45% of the AF patients were using warfarin before TBI or torso injury, and 35% before hip fracture. After injury, there was a dramatic and persistent decrease in warfarin use in TBI and torso injury groups (30% for TBI and 37% for torso injury at 12 months after injury). Warfarin usage in hip fracture patients also dropped after injury but returned to pre-injury level within 4 months. TBI and torso injury lead to significant decreases in warfarin usage in elderly AF patients. Further research is needed to understand reasons for the pattern and to develop evidence-based management strategies in the post-acute setting.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Brain Injuries; Drug Utilization; Fee-for-Service Plans; Female; Hip Fractures; Humans; Male; Medicare; Torso; United States; Warfarin

Previous studies of traumatic brain injury (TBI) outcomes in elderly patients on oral antithrombotic (OAT) therapies have yielded conflicting results. Our objective was to examine the effect of premorbid OAT medications on outcomes among elderly TBI patients with intracranial hemorrhage.. We performed a retrospective analysis of elderly TBI patients (≥65 years) with closed head injury and evidence of brain hemorrhage on computed tomography scan from 2006 to 2010. Patient demographics, injury severity, clinical course, hospital and intensive care unit length of stay, and disposition were collected. Comparison of patients stratified by premorbid OAT use was performed using nonparametric Kruskal-Wallis and Fisher's exact tests. Multivariable logistic regression was used to compare groups and identify predictors of primary outcomes, including mortality, neurosurgical intervention, hemorrhage progression, complications, and infection.. A total of 1,552 patients were identified: 543 on aspirin only, 97 on clopidogrel only, 218 on warfarin only, 193 on clopidogrel and aspirin, and 501 on no antithrombotic agent. Blood products were administered to reverse coagulopathy in 77.3% of patients on antithrombotic medications. After adjusting for covariates, including medication reversal, OAT use was associated with increased mortality (p = 0.04). Warfarin use was identified as a key predictor (odds ratio, 2.27; p = 0.05), in contrast to the preinjury use of antiplatelet medications, which was not associated with increased risk of in-hospital death. Rates of neurosurgical intervention differed between groups, with patients on warfarin undergoing intervention more frequently. Survivor subset analysis demonstrated that hemorrhage progression was not associated with preinjury antithrombotic therapy, nor were rates of complication or infection, hospital and intensive care unit lengths of stay, or ventilator days.. Preinjury use of warfarin, but not antiplatelet medications, influences survival and need for neurosurgical intervention in elderly TBI patients with intracranial hemorrhage; hemorrhage progression and morbidity are not affected. The importance of antithrombotic therapy may lie in its impact on initial injury severity.. Epidemiologic study, level III.

Topics: Administration, Oral; Aged; Anticoagulants; Aspirin; Brain Injuries; Clopidogrel; Female; Humans; Intracranial Hemorrhages; Length of Stay; Male; Platelet Aggregation Inhibitors; Retrospective Studies; Survival Rate; Ticlopidine; Tomography, X-Ray Computed; Trauma Severity Indices; Warfarin

Despite recent progress, prognosis for the elderly (defined as aged ≥70 years) afflicted by traumatic brain injury (TBI) is unfavorable and surgical intervention remains controversial. Research during the past decade on the mortality rates or prognostic factors for survival in the elderly is limited.. We analyzed 97 patients aged ≥70 years who were treated surgically for closed TBI at our neurosurgical unit between January 1, 2003 and December 31, 2012. In addition, we analyzed 22 patients aged ≥70 years who had sustained a closed TBI and on whom no neurosurgical intervention was performed. Outcome in both groups was measured as 30-, 90- and 180-day mortality.. Surgically treated patients: median age, 76 years' 30-day overall mortality rate, 36%. Higher mortality was seen with lower level of consciousness, high energy trauma, one pupil fixed and dilated, and more extensive intracranial pathology. Presence of warfarin, more advanced age, or degree of midline shift were not associated with worsened outcome. Patients not treated neurosurgically: median age. 81.5 years; 30-day overall mortality rate, 23%. Mortality for patients with Glasgow coma scale (GCS) 10-15 was 6%, GCS 6-9 67%, and GCS 3-5 100%.. Selected patients aged ≥70 years can benefit from surgical intervention for closed TBI. Level of consciousness, radiologic type of injury, mechanism of injury, and pupil abnormalities should be carefully evaluated. There also seems to exist a group of patients in whom surgical intervention offers little benefit, as mortality rate is low without surgical intervention.

Topics: Acute Disease; Age Factors; Aged; Aged, 80 and over; Anticoagulants; Brain Injuries; Craniotomy; Female; Glasgow Coma Scale; Head Injuries, Closed; Hematoma, Subdural; Humans; Male; Prognosis; Retrospective Studies; Risk Factors; Sweden; Treatment Outcome; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Brain Injuries; Female; Hemorrhage; Humans; Male; Risk Assessment; Thrombosis; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Brain Injuries; Female; Hemorrhage; Humans; Male; Risk Assessment; Thrombosis; Warfarin

Current literature estimates the risk of delayed intracranial hemorrhage as between 0.6 and 6% after mild head injury for patients on warfarin. Due to resource allocation issues, the need to actually diagnose delayed intracranial haemorrhage has been questioned, especially if it does not require surgery. The purpose of our case report is to consider the functional implications during the six months following a mild traumatic brain injury complicated by delayed intracranial hemorrhage in a patient undergoing warfarin therapy. To the best of our knowledge, the rehabilitative and functional considerations of delayed intracranial haemorrhage in head injury have not been previously described in the literature.. A previously independent 74-year-old Lebanese man living in Australia sustained mild traumatic brain injury following an unwitnessed fall from the height of two meters while on warfarin therapy, with an international normalized ratio of 4.2. He was found to have amnesia of the event and extensive facial bruising. His Glasgow Coma Scale score was 14 to 15 throughout observation. Following a non-diagnostic initial computerised tomography scan, a repeat scan at 24 hours from the injury identified large intracerebral, subdural and subarachnoid hemorrhages. A detailed examination demonstrated visuospatial and cognitive impairments. He required inpatient rehabilitation for three weeks, and outpatient rehabilitation for two months. By six months, he had returned to his pre-injury level of functioning, but was unable to resume driving.. We describe rehabilitation outcomes of delayed intracranial haemorrhage and mild traumatic brain injury, with diminishing disability over six months. In our case report, the complication of the delayed intracranial haemorrhage resulted in significant activity limitations and participation restrictions, which affected the clinical management, including the need for multidisciplinary rehabilitation. The risk of delayed intracranial haemorrhage in mild head injury remains a significant problem requiring further research.

Topics: Aged; Anticoagulants; Brain Injuries; Glasgow Coma Scale; Humans; Intracranial Hemorrhages; Male; Time Factors; Tomography, X-Ray Computed; Warfarin

To determine the percentage of patients with correction of their first international normalized ratio (INR) less than 1.5 after administration of moderate-dose three-factor prothrombin complex concentrate (PCC), 35 IU/kg compared with low-dose PCC, 25 IU/kg.. Retrospective review.. Community teaching hospital.. A total of 42 adult patients diagnosed with warfarin-associated traumatic brain injury (TBI) presented with an INR of 1.5 or more and received at least one dose of PCC during a 19-month study period. The low-dose group received PCC 25 IU/kg from November 2011-July 2012 and the moderate-dose group received PCC 35 IU/kg from August 2012-May 2013.. Of the 42 patients, 25 were in the low-dose group and 17 were in the moderate-dose group. Baseline characteristics were similar between both groups in regard to age, sex, weight, creatinine clearance, weekly warfarin dose, initial INR, initial Glasgow Coma Score, and injury severity score. Of the patients in the low-dose group, 12% achieved INR reversal with first measured INR after PCC administration compared with 69% in the moderate-dose group (p<0.001). The median time to INR reversal was 6.9 hours in the low-dose PCC group and 1.9 hours in the moderate-dose PCC group (p=0.04). There were no differences between the groups in other secondary end points, including stabilization of TBI, days in the intensive care unit, total days of hospitalization, blood product administration, and adverse events.. Moderately dosed PCC at 35 IU/kg compared with a lower dosage of 25 IU/kg was associated with a higher percentage of INR reversal and more rapid time to INR normalization in patients with TBI. Future randomized controlled studies to further investigate this novel dose and the impact on potential reductions in the use of fresh frozen plasma are warranted.

Topics: Aged; Aged, 80 and over; Anticoagulants; Blood Coagulation Factors; Brain Injuries; Dose-Response Relationship, Drug; Female; Humans; International Normalized Ratio; Male; Pilot Projects; Retrospective Studies; Warfarin

Anticoagulation agents are proven risk factors for intracranial hemorrhage (ICH) in traumatic brain injury (TBI). The aim of our study is to describe the epidemiology of prehospital coumadin, aspirin, and Plavix (CAP) patients with ICH and evaluate the use of repeat head computed tomography (CT) in this group. We performed a retrospective study from our trauma registry. All patients with intracranial hemorrhage on initial CT with prehospital CAP therapy were included. Demographics, CT scan findings, number of repeat CT scans, progressive findings, and neurosurgical intervention were abstracted. A comparison between prehospital CAP and no-CAP patients was done using χ(2) and Mann-Whitney U test. A total of 1606 patients with blunt TBI charts were reviewed of whom 508 patients had intracranial bleeding on initial CT scan and 72 were on prehospital CAP therapy. CAP patients were older (P < 0.001), had higher Injury Severity Score and head Abbreviated Injury Scores on admission (P < 0.001), were more likely to present with an abnormal neurologic examination (P = 0.004), and had higher hospital and intensive care unit lengths of stay (P < 0.005). Eighty-four per cent of patients were on antiplatelet therapy and 27 per cent were on warfarin. The CAP patients have a threefold increase in the rate of worsening repeat head CT (26 vs 9%, P < 0.05). Prehospital CAP therapy is high risk for progression of bleeding on repeat head CT. Routine repeat head CT remains an important component in this patient population and can provide useful information.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Aspirin; Brain Injuries; Clopidogrel; Cohort Studies; Disease Progression; Female; Head Injuries, Closed; Humans; Intracranial Hemorrhages; Logistic Models; Male; Middle Aged; Multivariate Analysis; Registries; Retrospective Studies; Risk Factors; Ticlopidine; Tomography, X-Ray Computed; Warfarin

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.

Topics: Animals; Anticoagulants; Benzimidazoles; beta-Alanine; Blood Coagulation; Blood Coagulation Factors; Brain; Brain Injuries; Cerebral Hemorrhage; Dabigatran; Hemorrhage; Mice; Mice, Inbred C57BL; Warfarin

The increased risk of hemorrhage associated with anticoagulant therapy following traumatic brain injury creates a serious dilemma for medical management of older patients: Should anticoagulant therapy be resumed after traumatic brain injury, and if so, when?. To estimate the risk of thrombotic and hemorrhagic events associated with warfarin therapy resumption following traumatic brain injury.. Retrospective analysis of administrative claims data for Medicare beneficiaries aged at least 65 years hospitalized for traumatic brain injury during 2006 through 2009 who received warfarin in the month prior to injury (n = 10,782).. Warfarin use in each 30-day period following discharge after hospitalization for traumatic brain injury.. The primary outcomes were hemorrhagic and thrombotic events following discharge after hospitalization for traumatic brain injury. Hemorrhagic events were defined on inpatient claims using International Classification of Diseases, Ninth Revision, Clinical Modification codes and included hemorrhagic stroke, upper gastrointestinal bleeding, adrenal hemorrhage, and other hemorrhage. Thrombotic events included ischemic stroke, pulmonary embolism, deep venous thrombosis, and myocardial infarction. A composite of hemorrhagic or ischemic stroke was a secondary outcome.. Medicare beneficiaries with traumatic brain injury were predominantly female (64%) and white (92%), with a mean (SD) age of 81.3 (7.3) years, and 82% had atrial fibrillation. Over the 12 months following hospital discharge, 55% received warfarin during 1 or more 30-day periods. We examined the lagged effect of warfarin use on outcomes in the following period. Warfarin use in the prior period was associated with decreased risk of thrombotic events (relative risk [RR], 0.77 [95% CI, 0.67-0.88]) and increased risk of hemorrhagic events (RR, 1.51 [95% CI, 1.29-1.78]). Warfarin use in the prior period was associated with decreased risk of hemorrhagic or ischemic stroke (RR, 0.83 [95% CI, 0.72-0.96]).. Results from this study suggest that despite increased risk of hemorrhage, there is a net benefit for most patients receiving anticoagulation therapy, in terms of a reduction in risk of stroke, from warfarin therapy resumption following discharge after hospitalization for traumatic brain injury.

Topics: Adrenal Gland Diseases; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Brain Injuries; Brain Ischemia; Female; Gastrointestinal Hemorrhage; Hemorrhage; Humans; Intracranial Hemorrhages; Male; Myocardial Infarction; Pulmonary Embolism; Retrospective Studies; Risk Assessment; Stroke; Thrombosis; Venous Thrombosis; Warfarin

Warfarin-associated intracranial hemorrhage is associated with a high mortality rate. Ongoing coagulopathy increases the likelihood of hematoma expansion and can result in catastrophic hemorrhage if surgery is performed without reversal. The current standard of care for emergency reversal of warfarin is with fresh frozen plasma (FFP). In April 2013, the USA Food and Drug Administration approved a new reversal agent, 4-factor prothrombin complex concentrate (PCC), which has the potential to more rapidly correct coagulopathy. We sought to determine the feasibility and outcomes of using PCC for neurosurgical patients. A prospective, observational study of all patients undergoing coagulopathy reversal for intracranial hemorrhage from April 2013 to December 2013 at a single, tertiary care center was undertaken. Thirty three patients underwent emergent reversal of coagulopathy using either FFP or PCC at the discretion of the treating physician. Intracranial hemorrhage included subdural hematoma, intraparenchymal hematoma, and subarachnoid hemorrhage. FFP was used in 28 patients and PCC was used in five patients. International normalized ratio at presentation was similar between groups (FFP 2.9, PCC 3.1, p=0.89). The time to reversal was significantly shorter in the PCC group (FFP 256 minutes, PCC 65 minutes, p<0.05). When operations were performed, the time delay to perform operations was also significantly shorter in the PCC group (FFP 307 minutes, PCC 159 minutes, p<0.05). In this preliminary experience, PCC appears to provide a rapid reversal of coagulopathy. Normalization of coagulation parameters may prevent further intracranial hematoma expansion and facilitate rapid surgical evacuation, thereby improving neurological outcomes.

Topics: Anticoagulants; Antidotes; Blood Coagulation Factors; Brain Injuries; Hemorrhage; Humans; International Normalized Ratio; Intracranial Hemorrhages; Plasma; Practice Guidelines as Topic; Prospective Studies; Randomized Controlled Trials as Topic; Spinal Diseases; Subarachnoid Hemorrhage; Tertiary Care Centers; Warfarin

Patients on warfarin who have traumatic intracranial haemorrhage have a high mortality. The procoagulant recombinant factor VIIa (rFVIIa) is widely used off-label to treat intracranial haemorrhaging in patients taking warfarin to try to improve these adverse outcomes, but its effectiveness is unknown. In this study, medical records from 2002 to 2010 were reviewed for 27 warfarin patients who received rFVIIa for their traumatic intracranial haemorrhage and were compared with a matched control group of 27 warfarin patients who did not receive rFVIIa. The two groups were matched for sex, age and Injury Severity Score. The rFVIIa patients had 33.3% mortality compared with the 37% for the control patients, but this was not a statistically significant difference. There was also no significant difference in plasma unit use between the groups. However, the rFVIIa group had a significantly higher number of subdural haemorrhages, which carry a better prognosis. The initial international normalized ratios (INRs) of the rFVIIa patients were higher, and the decrease of INR was more pronounced than in the control patients. From the data, it appears that although the INRs of rFVIIa patients did improve compared with the control group, there was no reduction in plasma use or mortality.

Topics: Aged; Anticoagulants; Brain Injuries; Case-Control Studies; Coagulants; Factor VIIa; Female; Humans; Injury Severity Score; Intracranial Hemorrhage, Traumatic; Male; Recombinant Proteins; Retrospective Studies; Survival Analysis; Treatment Outcome; Warfarin

Relatively few pharmacological agents are part of routine care for neural injury, although several are used or under consideration in acute stroke, chronic stroke, traumatic brain injury and secondary stroke prevention. Tissue plasminogen activator is approved for the treatment of acute ischemic stroke, and genetic variants may impact the efficacy and safety of this drug. In the chronic phase of stroke, several drugs such as L-dopa, fluoxetine and donepezil are under investigation for enhancing rehabilitation therapy, with varying levels of evidence. One potential reason for the mixed efficacy displayed by these drugs may be the influence of genetic factors that were not considered in prior studies. An understanding of the genetics impacting the efficacy of dopaminergic, serotonergic and cholinergic drugs may allow clinicians to target these potential therapies to those patients most likely to benefit. In the setting of stroke prevention, which is directly linked to neural injury recovery, the most highly studied pharmacogenomic interactions pertain to clopidogrel and warfarin. Incorporating pharmacogenomics into neural injury recovery has the potential to maximize the benefit of several current and potential pharmacological therapies and to refine the choice of pharmacological agent that may be used to enhance benefits from rehabilitation therapy.

Topics: Anticoagulants; Brain Injuries; Clopidogrel; Humans; Pharmacogenetics; Platelet Aggregation Inhibitors; Recovery of Function; Stroke; Ticlopidine; Warfarin

The rapid reversal of warfarin in the setting of traumatic brain injury (TBI) has been associated with improved outcomes. Until now, remote reversal of hypocoagulable states has not been possible in the prehospital environment. This manuscript describes the development and analysis of a prehospital plasma transfusion protocol to reverse warfarin at the earliest possible moment after TBI.. A retrospective review of all TBI patients receiving plasma transfusion(s) in the prehospital environment for warfarin reversal between February 2009 and September 2010 was conducted. Thawed plasma was carried on every air ambulance flight centered at the main campus.. A total of 2836 flights carried over 2500 units of thawed plasma throughout the study period. During this time, 16 patients received prehospital plasma resuscitation, five of who were on warfarin with a concurrent TBI. The median Injury Severity Score was 17 (8.5-27.5) with a median Glasgow Coma Score of 13 (8-15) and a mortality rate of 40%. A median of 2 (1.5-2.0) units of thawed plasma and 0 (0-0) units of RBCs were transfused en route. The pretransfusion point-of-care international normalized ratio improved from 3.1 (2.3-4.0) to 1.9 (1.3-3.6) upon trauma center admission (serum sample). One hundred percent of the transported, but unused, thawed plasma underwent subsequent transfusion prior to expiration.. Remote prehospital plasma transfusions effectively reverse anticoagulation secondary to warfarin administration in TBI patients. It is feasible to transfuse thawed plasma in the prehospital setting via remote damage control techniques without increasing waste. Prospective studies are needed to determine if this practice can improve outcomes in this population.

Topics: Adult; Air Ambulances; Anticoagulants; Blood Coagulation Disorders; Brain Injuries; Emergency Medical Services; Feasibility Studies; Humans; Plasma; Resuscitation; Retrospective Studies; Warfarin

The number of patients who are on long-term anticoagulation therapy while experiencing traumatic brain injury (TBI) is rising. This experimental study evaluated whether warfarin pre-treatment increases brain hemorrhage and worsens functional outcome after TBI, and whether the rapid reversal of anticoagulation after TBI prevents warfarin-exacerbated brain damage. Normal CD-1 mice (C) and mice pre-treated with warfarin (W) to an International Normalized Ratio of 3.5±0.9 underwent TBI using a controlled cortical impact model. Mean hemorrhage volume 24 h after TBI was 1.2±0.4 μL in C mice and 10.9±6.9 μL in W mice (p=0.029, n=4 per group). In a second study, anticoagulated mice received either saline (W-S) or prothrombin complex concentrate (W-PCC, 100 U/kg) intravenously 60 min after TBI. Anticoagulation reversal using PCC (W-PCC mice) reduced hemorrhage volumes as compared to W-S animals (7.3±6.0 versus 19.8±14.0 μL, p=0.045, n=8 per group). In a third study, we examined motor deficits and lesion volume in C, W-S, and W-PCC mice until 33 days after injury. Functional outcome and lesion volume were no different between groups (n=10 per group). In conclusion, we characterized an experimental model of TBI occurring during warfarin anticoagulation. Anticoagulation led to higher intracerebral blood volumes, but did not significantly worsen functional outcome. The rapid reversal of anticoagulation may be effective in preventing excess bleeding.

Topics: Animals; Anticoagulants; Brain Injuries; Disease Models, Animal; Hemorrhage; Intracranial Hemorrhages; Male; Mice; Recovery of Function; Warfarin

Practice-based research plays a pivotal role for improving patient care as its primary intent is to solve a clinical dilemma or problem encountered in clinical practice. Its results are immediately applicable to day-to-day clinical practice and essential to the growth of an evidence-based clinical practice. This review emphasizes the importance of this type of research. In addition, it serves to identify common sources for project conception and gives examples based on personal experiences of the author as a clinical practitioner, educator, and researcher. Common barriers to practice-based research are discussed as well as potential solutions offered for consideration.

Topics: Brain Injuries; Calcium; Enteral Nutrition; Evidence-Based Medicine; Food-Drug Interactions; Humans; Hypocalcemia; Insulin; Obesity; Pancreatitis; Phosphorus; Renal Insufficiency, Chronic; Research; Treatment Outcome; Warfarin

Of the 500,000 brain injuries in the United States annually, 80% are considered mild (mild traumatic brain injury). Unfortunately, 2% to 3% of them will subsequently deteriorate and result in severe neurologic dysfunction. Intracerebral changes in the elderly, chronic oral anticoagulation, and platelet inhibition may contribute to the development of intracranial bleeding after minor head injury. We sought to investigate the association of age and the use of anticoagulation and antiplatelet therapy with neurologic deterioration and the need for neurosurgical intervention in patients presenting with mild traumatic brain injury.. A retrospective review of all adult (>14 years) patients admitted to our Level I trauma service with a Glasgow Coma Scale (GCS) score of 14 to 15 who underwent neurosurgical intervention during their hospital stay was performed. Patients were stratified into two groups, age <65 years and age ≥ 65 years. Each group was then further stratified by the use of anticoagulants: warfarin, aspirin, clopidogrel, or a combination. Mechanism of injury, prehospital complaints, admission GCS, type of neurosurgical intervention, intensive care unit length of stay, hospital length of stay, and discharge disposition were evaluated. Z test and logistic regression were used to compare proportions or percentages from different groups.. Of the 7,678 patients evaluated during the study period, 101 (1.3%) required neurosurgical intervention. The ≥ 65 years population underwent significantly more interventions as did those patients on anticoagulants.. All patients aged 65 years or older who present with a GCS score of >13 after head trauma should undergo a screening computed tomography of the head regardless of prehospital use of anticoagulation. Patients younger than 65 years can be selectively screened based on presenting complaints and mechanism of injury provided they are not on anticoagulation.

Topics: Age Factors; Aged; Anticoagulants; Aspirin; Brain Injuries; Clopidogrel; Craniotomy; Decompressive Craniectomy; Glasgow Coma Scale; Humans; Intracranial Hemorrhages; Middle Aged; Retrospective Studies; Ticlopidine; Time Factors; Tomography, X-Ray Computed; Warfarin

Patients are living longer with cardiovascular disease managed with antiplatelet drugs. These seniors are asked to be more physically active and are prone to falls or injuries. Few have studied the mortality or morbidity from anticoagulants in patients with traumatic brain injuries (TBI). With the increasing use of clopidogrel in the elderly, studies on the consequences of TBI are warranted.. This is a retrospective case-controlled study using a trauma data registry of 3,817 closed head trauma cases (2001-2005). Patients with preinjury use of clopidogrel, aspirin or warfarin, and evidence of traumatic intracranial bleeding were identified (n = 131). These were compared with a frequency-matched control group (n = 178) with similar age, gender, Glasgow Coma Scale, and Injury Severity Scores. Main outcome measure included mortality, hospital or intensive care unit duration, and discharge disposition.. Of 131 patients on anticoagulants, patients on clopidogrel (n = 21) were more likely to die (OR = 14.7; 95% CI: 2.3-93.6) and be discharged to an inpatient long-term facility (OR = 3.25; 95%CI: 1.06-9.96). Length of hospital stay and intensive care unit stay were not different from control. Mortality in aspirin patients (n = 90) and warfarin patients (n = 20) did not differ from control. Warfarin patients had increased hospital and ICU stay (10.6 and 5.3 days) when compared with the control (4.7 and 0.9 days, respectively).. TBI patients on clopidogrel may have increased long-term disability and fatal consequences when compared with patients who are not on these drugs or on other anticoagulants. Patients on clopidogrel should be advised of safety when engaging in potentially dangerous activities to avoid the consequences of TBI.

Topics: Aged; Aspirin; Brain Damage, Chronic; Brain Injuries; Cardiovascular Diseases; Case-Control Studies; Clopidogrel; Disability Evaluation; Female; Glasgow Coma Scale; Humans; Length of Stay; Male; Platelet Aggregation Inhibitors; Prognosis; Registries; Retrospective Studies; Ticlopidine; Warfarin

The relationship between preinjury warfarin use and outcomes after traumatic brain injury in elderly trauma patients remains controversial. We hypothesized that, among elderly warfarin users, the degree of anticoagulation, rather than warfarin therapy itself, would predict the severity of traumatic brain injury.. Retrospective study (2004-2006) of all elderly trauma patients (age >/=65 years) who were evaluated by the trauma service at a Level I trauma center and underwent computed tomography of the head for suspicion of an intracranial injury was performed. Three cohorts were grouped: (1) warfarin users with an admission International Normalized Ratio >/=2 (therapeutic group), (2) warfarin users with an admission International Normalized Ratio <2 (nontherapeutic group), and (3) warfarin nonusers. Main outcome variables were presenting with a Glasgow Coma Scale (GCS) score

Topics: Aged; Aged, 80 and over; Analysis of Variance; Anticoagulants; Brain Injuries; Chi-Square Distribution; Female; Glasgow Coma Scale; Humans; International Normalized Ratio; Intracranial Hemorrhages; Male; Predictive Value of Tests; Retrospective Studies; Statistics, Nonparametric; Tomography, X-Ray Computed; Warfarin

Coumadin is widely used in the elderly population. Despite its widespread use, little is known about its effect on the outcome of elderly traumatic brain-injured patients. This study was undertaken to describe the outcomes of such a cohort.. Clinical material was identified from a Level I trauma center prospective head injury database, and a database obtained from the American College of Surgeons Committee on Trauma Verification and Review Committee from 1999 to 2002. Both databases contain many relevant variables, including age, sex, Glasgow Coma Scale (GCS) score, mechanism of injury, Injury Severity Score, International Normalized Ratio (INR), computed tomography (CT) findings, operative procedure, time to operating room, complications, length of stay, and outcome at hospital discharge.. For patients with GCS scores less than 8, average INR was 6.0, with almost 50% having an initial value greater than 5.0. Overall mortality was 91.5%. For the 77 patients with GCS scores of 13 to 15, average INR was 4.4. Overall mortality for this group was 80.6%. A subset of patients deteriorated to a GCS score of less than 10 just hours after injury, despite most having normal initial CT scans. Mortality in this group was 84%.. All patients on warfarin should have an INR performed, and a CT scan should be done in most anticoagulated patients. All supratherapeutically anticoagulated patients, as well as any anticoagulated patient with a traumatic CT abnormality, should be admitted for neurologic observation and consideration given to short term reversal of anticoagulation. Routine repeat CT scanning at 12 to 18 hours or when even subtle signs of neurologic worsening occur is a strong recommendation. A multi-institutional, prospective trial using these guidelines would be a first step toward demonstrating improved outcomes in the anticoagulated patient population after head trauma.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Brain Hemorrhage, Traumatic; Brain Injuries; Cohort Studies; Female; Glasgow Coma Scale; Hospital Mortality; Humans; Injury Severity Score; International Normalized Ratio; Length of Stay; Male; Middle Aged; Neurologic Examination; Outcome Assessment, Health Care; Patient Admission; Prognosis; Risk Factors; Survival Analysis; Tomography, X-Ray Computed; Warfarin

To determine the incidence of clinically significant intracranial injury in the anticoagulated patient suffering minor head trauma without loss of consciousness (LOC) or acute neurologic abnormality.. A retrospective chart review was performed based on a computerized search of electronic patient records from six community hospital EDs, one of which is a trauma center. Patients taking warfarin who sustained minor head trauma without LOC having no acute neurologic abnormalities treated from January 1994 to January 1996 were identified using a search of electronic ED records. Charts were reviewed for mechanism of injury, physical examination findings of head injury, and concomitant injury. Prothrombin time and head CT results were recorded if obtained. For those patients not receiving a head CT on ED evaluation, telephone follow-up was performed to determine outcome.. There were 65 patients meeting inclusion criteria. Thirty-eight patients had prothrombin times obtained, with ranges from 12.0 sec to 30.7 sec. There was no intracranial injury found in any of the 39 patients having a head CT. Additionally, follow-up on the 26 patients who did not undergo CT scanning revealed no evidence of complications related to their head injuries.. The incidence of clinically significant intracranial injury is extremely low in the anticoagulated patient suffering minor blunt head trauma without LOC or acute neurologic abnormality. CT scanning may not be necessary in these patients. Larger prospective studies are needed to confirm these findings.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Brain Injuries; Female; Humans; Male; Middle Aged; Retrospective Studies; Tomography, X-Ray Computed; Ultrasonography; Warfarin