Traumaticbrain injury (TBI) in the United States afflicts approximately 333 in 100,000 persons,1and more than 200,000 Americans are hospitalized each year after a TBI.2The prevalence of these injuries is biphasic in distribution, disproportionately affecting older adolescents and the elderly (> 65 years of age).3Outcomes after a TBI are influenced by several factors, such as the mechanism and severity of injury, the age of the patient and any comorbidities, and the use of anticoagulation. Prior studies have shown that patients on premorbid anticoagulation therapy experience worse outcomes after a TBI than those not on these medications.4–7Importantly, older patients are more likely to be on anticoagulants and experience worse outcomes after a TBI.4–7Amid an aging population, the prevalence of patients on anticoagulation, as well as of patients experiencing a TBI, is likely to rise.
There has been a sharp rise in the use of direct oral anticoagulants (DOACs) since their introduction in 2010.8The majority of prior studies have focused on the impact of vitamin K antagonists (VKAs) in TBI, whereas relatively few have evaluated the outcomes of TBI patients who use a DOAC. Unlike VKAs, in patients using DOACs who present after experiencing a TBI, the availability and cost of reversal agents can be prohibitive.
Clarifying the impact of anticoagulation on outcomes of patients with a TBI is critical to pre- and postinjury medical decision-making and patient counseling. VKAs and DOACs have overlapping indications, and understanding the risk of each class in the context of TBI may influence prescribing patterns. Outcome data in patients who use DOACs will guide postinjury decision-making for providers who care for and intervene on behalf of TBI patients. Death is not an uncommon outcome after a TBI and is even more common in the elderly and patients on anticoagulation.9–15We sought to compare the survival outcomes of TBI patients who were on DOACs or VKAs at the time of injury with those of patients who were not on an anticoagulation regimen and stratify risk based on underlying comorbidities, presenting symptomology, and injury mechanism. Similar to the existing data on VKAs, we postulated that patients on DOACs would experience worse outcomes than those not on anticoagulation medication but would have generally similar outcomes to patients using VKAs.
开云体育世界杯赔率
Patient Selection
Patients who experienced TBI with evidence of an intracranial hemorrhage (including epidural, subdural, subarachnoid, and intraparenchymal hemorrhages) from January 1, 2016, through December 30, 2022, were identified through review of a retrospective database at the University of Utah. Institutional review board approval for the database was provided without requirement of patient consent. Only adult patients (≥ 18 years) with radiologically confirmed acute intracranial hemorrhage at the time of trauma presentation were included.
Recorded Variables
从标识符相关的数据收集d patients included demographics, comorbidities, mechanism of injury, presenting Glasgow Coma Scale (GCS) score, Injury Severity Score (ISS), radiographic Marshall score, neurosurgical intervention (classified as bedside procedure or operative intervention), and intensive care and hospital length of stay (LOS). Premorbid anticoagulant or antiplatelet use and the use of reversal agents for anticoagulation were also recorded. Survival data were generated from date of known death or date of last follow-up.
Statistical Analysis
Data were collected using Excel version 16.73 (Microsoft Corporation). Statistical analyses were conducted primarily using the "survminer" package in R version 4.3.0 (The R Foundation for Statistical Computing). The chi-square or Fisher exact test was used for categorical variables where appropriate, and the one-way ANOVA test was used for continuous data. The Kaplan-Meier method was used to analyze survival, and a multivariable Cox proportional hazards model was used to determine covariate associations with risk of death.
To identify the effects of independent risk factors on mortality, we conducted data analysis in two phases. First, individual covariates were assessed using a univariable Cox proportional hazards model for death. Parameters independently predictive of death (p < 0.1) on bivariate analysis were tested for satisfaction of the proportional hazards assumption and were then combined into a multivariable Cox proportional hazards model, generating relevant hazard ratios (HRs) and 95% CIs. We conducted a similar analysis for 30-day mortality using a logistic regression model, generating relevant odds ratios (ORs) and 95% CIs.
The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines were used for this study.
Results
Patient Characteristics
Among 1822 trauma patients treated in 2016–2022, 1186 were found to have acute intracranial hemorrhage. Of these, 86 (7.3%) patients were on anticoagulant monotherapy, 85 (7.2%) patients were on antiplatelet monotherapy, and 16 (1.3%) patients were on concomitant antiplatelet and anticoagulant therapy at the time of trauma presentation. Overall, the majority of our cohort was male (811 patients, 68%), with a mean age of 48.1 ± 20.7 years, mean BMI of 26.1 ± 10.2, and mean Charlson Comorbidity Index (CCI) of 2.2 ± 2.5. At presentation, the mean GCS score was 9.5 ± 4.7, the mean ISS was 18.6 ± 10.7, and the mean Marshall score was 2.7 ± 1.2. The mechanisms of injury consisted of primarily ground-level fall (533, 45%), followed by motor vehicle accident (218, 18%), motorcycle/bike accident (129, 11%), sporting accident (99, 8%), assault injury (94, 8%), pedestrian injury (72, 6%), gunshot wound (27, 2%), and other injuries (14, 1%). The mean follow-up time of our cohort was 19.5 months.
When comparing patients on anticoagulation (DOAC or VKA) with patients not on anticoagulation in our group, patients on anticoagulation were found to be significantly older at presentation (p < 0.001) (Table 1). Similarly, patients on anticoagulation carried a higher CCI (p < 0.001). Mechanisms of injury also differed among these groups. In the DOAC and VKA groups, 41 (84%) and 46 (87%) patients, respectively, presented with a fall, whereas 446 (41%) presented with a fall in the no-anticoagulation group (p < 0.001). Furthermore, patients not on anticoagulation were more likely to present with a lower GCS score (p < 0.001) and a higher ISS (p < 0.001) and experience longer intensive care unit (p = 0.004) and overall hospital (p < 0.001) LOS. Notably, patients who were using VKAs at the time of presentation were more likely to receive a reversal agent than those using DOACs (28 [53%] vs 15 [31%], p < 0.001). Reversal agents for patients using DOACs included 4-factor prothrombin complex concentrate (4F-PCC; 13 patients, 27%) and andexanet alfa (2 patients, 4%). In contrast, patients using VKAs received intravenous or oral vitamin K (10 patients, 19%), 4F-PCC (15 patients, 28%), or fresh-frozen plasma (3 patients, 6%). Patients within the anticoagulation and no-anticoagulation groups did not differ significantly in sex (p = 0.91), BMI (p = 0.06), Marshall score (p = 0.48), and rates of neurosurgical intervention (p = 0.25).
Patient characteristics by anticoagulation status
| Characteristic | Anticoagulation Status at Time of Trauma | p Value | ||
|---|---|---|---|---|
| None (n = 1084) | DOAC (n = 49) | VKA (n = 53) | ||
| Demographics | ||||
| Age, yrs* | 51.3 ± 20.1 | 78.1 ± 11.3 | 71.1 ± 12.4 | <0.001 |
| Male sex | 751 (69) | 30 (61) | 30 (57) | 0.91 |
| BMI* | 26.8 ± 10.6 | 26.7 ± 6.0 | 30.2 ± 7.8 | 0.06 |
| CCI | 1.9 ± 2.3 | 4.7 ± 1.9 | 5.1 ± 2.3 | <0.001 |
| Antiplatelet therapy | 0.02 | |||
| Aspirin | 50 (5) | 6 (12) | 6 (11) | |
| P2Y12 receptor antagonist | 33 (3) | 1 (2) | 3 (6) | |
| Mechanism of injury | <0.001 | |||
| Fall | 446 (41) | 41 (84) | 46 (87) | |
| Motor vehicle accident | 211 (19) | 4 (8) | 3 (6) | |
| Motorcycle/bike accident | 127 (12) | 1 (2) | 1 (2) | |
| Sporting accident | 97 (9) | 1 (2) | 1 (2) | |
| Assault | 92 (8) | 1 (2) | 1 (2) | |
| Pedestrian | 71 (7) | 0 | 1 (2) | |
| Gunshot wound | 26 (2) | 1 (2) | 0 | |
| Other | 14 (1) | 0 | 0 | |
| Scores at presentation | ||||
| GCS score | 10.9 ± 4.8 | 13.1 ± 3.4 | 13.6 ± 3.1 | <0.001 |
| ISS | 22.4 ± 10.7 | 17.3 ± 9.8 | 17.6±9.1 | <0.001 |
| Marshall score | 2.7 ± 1.2 | 2.7 ± 1.1 | 2.5 ± 1.1 | 0.48 |
| Intervention | 0.25 | |||
| Bedside procedure† | 104 (10) | 1 (2) | 1 (2) | |
| Op intervention | 139 (13) | 5 (10) | 6 (11) | |
| Bedside & op interventions | 86 (8) | 5 (10) | 4 (8) | |
| Anticoagulation reversal | — | 15 (31) | 28 (53) | <0.001 |
| Vitamin K | — | — | 10 (19) | |
| 4F-PCC | — | 13 (27) | 15 (28) | |
| Fresh-frozen plasma | — | — | 3 (6) | |
| Andexanet alfa | — | 2 (4) | — | |
| Hospital LOS | ||||
| ICU | 6.4 ± 8.0 | 3.0 ± 3.0 | 4.7 ± 5.9 | 0.004 |
| Overall | 11.0 ± 10.2 | 6.6 ± 4.6 | 7.6 ± 5.1 | <0.001 |
| 30-day mortality | 105 (10) | 13 (27) | 10 (19) | <0.001 |
| Median OS, yrs | 10.7 | 2.5 | 2.3 | <0.001 |
ICU = intensive care unit.
Values are expressed as the number of patients (%) or mean ± SD unless otherwise indicated. Boldface type indicates a statistically significant difference between anticoagulant use and no anticoagulant use (p < 0.05).
Statistically significant difference between DOAC and VKA groups (p < 0.05).
Bedside procedures include external ventricular drainage and intracranial pressure monitoring.
Within the anticoagulation group, patients using DOACs were older (p = 0.042) (Table 1) and had a lower BMI (p = 0.020) than patients using VKAs. However, these groups were similar (p > 0.05) in all other included factors. Notably, overall survival (OS) among these two groups was also not statistically significantly different (p = 0.290).
Effects on Short-Term and Overall Survival
In our cohort, 30-day mortality was found to be significantly higher in patients with DOAC (27%) and VKA (19%) use when compared with patients without anticoagulation use (10%; p < 0.001). In a logistic regression model adjusting for age, ISS, Marshall score, CCI, presenting GCS score, reversal agent usage, and concomitant antiplatelet use, DOAC use (OR 2.513, p = 0.045) but not VKA use (OR 2.223, p = 0.138) carried an increased risk of 30-day mortality compared with no anticoagulation use (Table 2). Greater age (OR 1.045, p < 0.001), ISS (OR 1.037, p < 0.001), and Marshall score (OR 1.316, p < 0.001) were associated with an increased risk of 30-day mortality in our cohort. Meanwhile, a higher GCS score at presentation (OR 0.859, p < 0.001) was significantly associated with a decreased risk of 30-day mortality. Antiplatelet use (aspirin or P2Y12 receptor blockers), CCI, and anticoagulation reversal were not associated with changes in risk of mortality (p > 0.05).
Multivariate logistic regression model for 30-day mortality of all patients
| Variable | Logistic Regression Model | |
|---|---|---|
| Multivariate OR (95% CI) | p Value | |
| Age at presentation* | 1.045 (1.028–1.064) | <0.001 |
| Anticoagulant use | ||
| No anticoagulation | Reference | |
| DOAC | 2.513 (1.021–6.186) | 0.045 |
| Oral VKA | 2.223 (0.773–6.394) | 0.138 |
| Antiplatelet use | ||
| No antiplatelets | Reference | |
| Aspirin | 1.221 (0.507–2.940) | 0.656 |
| P2Y12 receptor antagonist | 1.846 (0.716–4.759) | 0.205 |
| GCS score at presentation* | 0.859 (0.819 - -0.900) | <0.001 |
| Marshall score* | 1.316 (1.128–1.534) | <0.001 |
| ISS* | 1.037 (1.016–1.058) | <0.001 |
| CCI* | 0.959 (0.838–1.096) | 0.537 |
| Anticoagulation reversal | ||
| No | Reference | |
| Yes | 1.215 (0.419–3.523) | 0.72 |
Boldface type indicates a statistically significant difference (p < 0.05).
Variable is continuous and increasing.
Patients with DOAC and VKA use demonstrated significantly lower OS in our cohort, with median OS times of 30.9 and 27.7 months, respectively. In contrast, patients without anticoagulation use demonstrated a median OS of 128.7 months (p < 0.001) (Fig. 1). In a Cox proportional hazards model for death adjusting for age, ISS, Marshall score, CCI, presenting GCS score, reversal agent usage, and concomitant antiplatelet use, both DOAC (HR 1.973, p = 0.007) and VKA (HR 2.204, p = 0.003) use carried an increased risk of death compared with no anticoagulation use (Table 3). Greater age (HR 1.040, p < 0.001), ISS (HR 1.017, p = 0.01), and Marshall score (HR 1.186, p < 0.001) were associated with an increased risk of death in our cohort. In contrast, a higher GCS score at presentation (HR 0.912, p < 0.001) was significantly associated with a decreased risk of death. Antiplatelet use (aspirin or P2Y12 receptor blockers), CCI, and anticoagulation reversal were not associated with changes in risk of mortality (p > 0.05).
Kaplan-Meier survival analysis of TBI patients stratified by anticoagulation status at the time of trauma. anticoag = anticoagulation.
Cox proportional hazards multivariate regression model for mortality of all patients
| Variable | Cox Proportional Hazards Regression Model | |
|---|---|---|
| Multivariate HR (95% CI) | p Value | |
| Age at presentation* | 1.040 (1.028–1.051) | <0.001 |
| Anticoagulant use | ||
| No anticoagulation | Reference | |
| DOAC | 1.973 (1.209–3.219) | 0.007 |
| Oral VKA | 2.204 (1.314–3.696) | 0.003 |
| Antiplatelet use | ||
| No antiplatelets | Reference | |
| Aspirin | 1.543 (0.979–2.431) | 0.06 |
| P2Y12 receptor antagonist | 0.869 (0.480–1.571) | 0.64 |
| GCS score at presentation* | 0.912 (0.886–0.939) | <0.001 |
| Marshall score* | 1.186 (1.079–1.304) | <0.001 |
| ISS* | 1.017 (1.004–1.030) | 0.01 |
| CCI* | 1.058 (0.986–1.135) | 0.12 |
| Anticoagulation reversal | ||
| No | Reference | |
| Yes | 0.732 (0.408–1.312) | 0.29 |
Boldface type indicates a statistically significant difference (p < 0.05).
Variable is continuous and increasing.
Discussion
DOACs are considered an effective, safe, manageable, and overall well-tolerated form of anticoagulation, especially when compared with oral VKAs.16–20Before the introduction of DOACs, more than 10% of adults older than 65 years of age used VKAs.4Although some indications remain for the use of VKAs, such as prosthetic valves or antiphospholipid syndrome, DOACs are now preferred for most patients requiring anticoagulation. DOACs require less frequent monitoring than VKAs and reduce the risk of major bleeding and death;16however, despite their favorable risk profile in initial studies comparing the safety of DOACs and VKAs, DOAC use may lead to poor outcomes after head trauma. Clarifying the effect of these agents on patients with TBI is essential to pre- and postinjury medical decision-making.
Prior studies have evaluated the effects of preinjury VKA (specifically warfarin) use and found that the risks of mortality and adverse outcomes after a TBI were significantly higher than those for patients not on anticoagulation therapy.4,5,10,11,13–15Among the studies that have assessed the effect of preinjury DOAC use, some have demonstrated little difference in mortality between patients on DOACs and those on VKAs,21–26others have shown better outcomes for patients taking a DOAC,27–33and some have seen worse outcomes for patients with TBI using DOACs.34,35Our study seeks to further clarify this question and stratify risk based on presentation GCS score, comorbidities, and the use of anticoagulation reversal agents.
The present study reveals that among patients with TBI, the risk of death was relatively similar in patients who were on VKAs and DOACs, after adjusting for age, comorbidities, and injury mechanism, although our findings are consistent with prior studies that found that increasing age, injury severity, and comorbidities led to worse outcomes. Patients who experience TBI are at a higher risk of all-cause mortality following hospitalization. We found that preinjury DOAC use led to a shorter median OS after a TBI than was seen in patients not on anticoagulation. However, the median OS was only marginally higher for patients on DOACs than for those on VKAs.
重要的是,患者创伤性脑损伤的while on either a VKA or DOAC more frequently experienced a mild mechanism of injury and had a higher initial GCS score. The majority of motor vehicle accidents, assaults, sporting accidents, and gunshot wounds were experienced by younger patients not on anticoagulation. Falls are currently the leading cause of head trauma and most often occur in the elderly, who are also more likely to be on anticoagulation medication.7Patients who are older, receiving anticoagulation therapy, and more prone to a TBI after minor injuries are more likely to have a higher CCI. In our cohort, antiplatelet use failed to demonstrate a significant impact on OS, which aligns with prior literature.5Also, in our study, patients with a higher Marshall score more often experienced death after a TBI. As the indications for VKA and DOAC use diverge, further studies clarifying the impact of specific comorbidities in each patient population may elucidate novel treatment strategies and management approaches.
Prior literature has evaluated the use of reversal agents in patients on anticoagulation who experience a TBI and found opposing outcomes, with some claiming benefit36,37and others demonstrating equivocal or worse outcomes22,26,38with their use. Most current literature evaluating the use of reversal agents in these patients focuses on laboratory evidence of anticoagulation status such as the international normalized ratio and radiographic evidence of intracranial hemorrhage progression rather than clinical outcome.37,39–43In our cohort, patients on VKAs were more likely to undergo reversal, which is consistent with the current literature. At present, the benefits and indications for use of DOAC reversal agents (such as andexanet alfa) after a TBI are still relatively unclear. This, in combination with limited availability and prohibitive cost, leads to infrequent use in many clinical settings. We found that anticoagulation reversal was associated with a decreased rate of death, but the decrease was not statistically significant. The interpretation of our results, and that of previous research, is limited by a variable treatment pattern among physicians, timing of reversal, and clinical indication. Many physicians choose to use reversal agents depending on the severity of injury, imaging characteristics, age, anticoagulant, and time to presentation rather than applying reversal agents universally in the presence of anticoagulation. Additional prospective studies are needed to clarify the role of reversal agents in TBI patients on anticoagulation and to assess the potential effect of reversal on clinical outcome and death, specifically.
Limitations
这项工作包括retrospec的局限性tive nature of the study. In addition, our sample consisted of patients treated at a level I trauma center in the Intermountain West and thus may not be reflective of a more heterogeneous population treated in a different region of the United States or internationally. Many patients in our cohort were transferred from surrounding states and, as a result, had limited records for follow-up after discharge, which impacted our overall follow-up time. In addition, the criteria for reversal of anticoagulation varied widely among transfer centers, thereby adding inherent heterogeneity in patient management, which could impact overall outcomes. Furthermore, restarting anticoagulation for many patients was decided through collaboration among the neurosurgery, trauma surgery, and consulting team physicians. This collaboration introduced variation in clinical care that could impact short- and long-term mortality, but we believe that this is beyond the scope of this present work. Our anticoagulation and non-anticoagulation cohorts differed significantly in size, which could impact our ability to detect small differences between these groups. Although we did attempt to control for factors that may independently influence survival (such as age and comorbidity burden), there are potential frailty metrics that were not captured in our study that may have impacted outcomes significantly. Finally, as reversal agents for DOACs are becoming more available, the administration of these medications may become more widespread and lead to improved outcomes.
Conclusions
我们的研究结果表明,反的受伤前使用coagulation medications portends a worse outcome after a TBI, although patients with a higher initial GCS score and a lower ISS and Marshall score experienced death less often after a TBI. In the context of conflicting literature, we draw attention to the fact that patients on oral VKAs had overall similar outcomes to patients on DOACs after adjusting for injury mechanism, age, and comorbidities. Additional prospective and multicenter studies will bolster the current body of evidence and clarify the risks of anticoagulation and use of reversal agents in patients after a TBI.
Disclosures
作者报告无利益冲突问题ing the materials or methods used in this study or the findings specified in this paper.
Author Contributions
Conception and design: Grandhi, Botros. Acquisition of data: Botros, Gautam, Nguyen, Cortez. Analysis and interpretation of data: Grandhi, Botros, Hamrick, Nguyen, Young, McCrum. Drafting the article: Botros, Gautam, Hamrick, Young. Critically revising the article: Grandhi, Botros, Hamrick, Young, Lombardo, McCrum, Menacho. Reviewed submitted version of manuscript: Grandhi, Botros, Gautam, Hamrick, Nguyen, Young, Lombardo, McCrum, Menacho. Approved the final version of the manuscript on behalf of all authors: Grandhi. Statistical analysis: Botros. Administrative/technical/material support: Grandhi. Study supervision: Grandhi.
Supplemental Information
Videos
Video Abstract.https://vimeo.com/861637683.
References
-
1 ↑
Global, regional, and national burden of traumatic brain injury and spinal cord injury, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016.Lancet Neurol.2019;18(1):56–87.
-
2 ↑
Surveillance Report of Traumatic Brain Injury-related Hospitalizations and Deaths by Age Group, Sex, and Mechanism of Injury—United States, 2016 and 2017. Centers for Disease Control and Prevention,.US Department of Health and Human Services;2021.Accessed August 4, 2023.https://www.cdc.gov/traumaticbraininjury/pdf/TBI-surveillance-report-2016-2017-508.pdf
-
3 ↑
CorriganJD,SelassieAW,OrmanJA.The epidemiology of traumatic brain injury.J Head Trauma Rehabil.2010;25(2):72–80.
-
4 ↑
DossettLA,RieselJN,GriffinMR,CottonBA.Prevalence and implications of preinjury warfarin use: an analysis of the National Trauma Databank.Arch Surg.2011;146(5):565–570.
-
5 ↑
GrandhiR,HarrisonG,VoronovichZ,et al.Preinjury warfarin, but not antiplatelet medications, increases mortality in elderly traumatic brain injury patients.J Trauma Acute Care Surg.2015;78(3):614–621.
-
6
FrankoJ,KishKJ,O’ConnellBG,SubramanianS,YuschakJV.Advanced age and preinjury warfarin anticoagulation increase the risk of mortality after head trauma.J Trauma.2006;61(1):107–110.
-
7 ↑
RoozenbeekB,MaasAI,MenonDK.Changing patterns in the epidemiology of traumatic brain injury.Nat Rev Neurol.2013;9(4):231–236.
-
8 ↑
AlalwanAA,VoilsSA,HartzemaAG.Trends in utilization of warfarin and direct oral anticoagulants in older adult patients with atrial fibrillation.Am J Health Syst Pharm.2017;74(16):1237–1244.
-
9 ↑
BatchelorJS,GraysonA.A meta-analysis to determine the effect of preinjury antiplatelet agents on mortality in patients with blunt head trauma.Br J Neurosurg.2013;27(1):12–18.
-
10 ↑
CollinsCE,WitkowskiER,FlahiveJM,AndersonFAJr,SantryHP.Effect of preinjury warfarin use on outcomes after head trauma in Medicare beneficiaries.Am J Surg.2014;208(4):544–549.e1.
-
11 ↑
InamasuJ,NakatsukasaM,MiyatakeS,HiroseY.Influence of warfarin and low-dose aspirin on the outcomes of geriatric patients with traumatic intracranial hemorrhage resulting from ground-level fall.Geriatr Gerontol Int.2012;12(4):667–672.
-
12
PeckKA,CalvoRY,SchechterMS,et al.The impact of preinjury anticoagulants and prescription antiplatelet agents on outcomes in older patients with traumatic brain injury.J Trauma Acute Care Surg.2014;76(2):431–436.
-
13 ↑
NarumS,BrørsO,StoklandO,KringenMK.Mortality among head trauma patients taking preinjury antithrombotic agents: a retrospective cohort analysis from a Level 1 trauma centre.BMC Emerg Med.2016;16(1):29.
-
14
BoltzMM,PodanyAB,HollenbeakCS,ArmenSB.Injuries and outcomes associated with traumatic falls in the elderly population on oral anticoagulant therapy.Injury.2015;46(9):1765–1771.
-
15 ↑
QiuL,HanJX,SeeAAQ,KingNKK.Effects of anticoagulant and antiplatelet agents in severe traumatic brain injury in an Asian population—a matched case-control study.J Clin Neurosci.2019;70:61–66.
-
16 ↑
VinogradovaY,CouplandC,HillT,Hippisley-CoxJ.Risks and benefits of direct oral anticoagulants versus warfarin in a real world setting: cohort study in primary care.BMJ.2018;362:k2505.
-
17
WelanderF,RenlundH,DiményE,HolmbergH,SjälanderA.Direct oral anticoagulants versus warfarin in patients with non-valvular atrial fibrillation and CKD G3-G5D.Clin Kidney J.2023;16(5):835–844.
-
18
ZengS,ZhengY,JiangJ,MaJ,ZhuW,CaiX.Effectiveness and safety of DOACs vs. warfarin in patients with atrial fibrillation and frailty: a systematic review and meta-analysis.Front Cardiovasc Med.2022;9:907197.
-
19
WadsworthD,SullivanE,JackyT,SpragueT,FeinmanH,KimJ.A review of indications and comorbidities in which warfarin may be the preferred oral anticoagulant.J Clin Pharm Ther.2021;46(3):560–570.
-
20 ↑
XianY,XuH,O’BrienEC,et al.直接口服anticoagulan临床疗效ts vs warfarin in older patients with atrial fibrillation and ischemic stroke: findings from the Patient-Centered Research Into Outcomes Stroke Patients Prefer and Effectiveness Research (PROSPER) study.JAMA Neurol.2019;76(10):1192–1202.
-
21 ↑
HechtJP,LaDukeZJ,Cain-NielsenAH,HemmilaMR,WahlWL.Effect of preinjury oral anticoagulants on outcomes following traumatic brain injury from falls in older adults.Pharmacotherapy.2020;40(7):604–613.
-
22 ↑
KobayashiL,BarmparasG,BosargeP,et al.Novel oral anticoagulants and trauma: the results of a prospective American Association for the Surgery of Trauma Multi-Institutional Trial.J Trauma Acute Care Surg.2017;82(5):827–835.
-
23
ScottiP,SéguinC,LoBWY,de GuiseE,TroquetJM,MarcouxJ.Antithrombotic agents and traumatic brain injury in the elderly population: hemorrhage patterns and outcomes.J Neurosurg.2020;133(2):486–495.
-
24
AntoniA,WedrichL,SchauperlM,et al.Management of traumatic brain injury in patients with DOAC therapy—are the "new" oral anticoagulants really safer?J Clin Med.2022;11(21):6268.
-
25
BarlettaJF,HallS,SucherJF,DzanduJK,HaleyM,MangramAJ.The impact of pre-injury direct oral anticoagulants compared to warfarin in geriatric G-60 trauma patients.Eur J Trauma Emerg Surg.2017;43(4):445–449.
-
26 ↑
MyersSP,DadashzadehER,CheungJ,et al.Management of anticoagulation with rivaroxaban in trauma and acute care surgery: complications and reversal strategies as compared to warfarin therapy.J Trauma Acute Care Surg.2017;82(3):542–549.
-
27 ↑
PrexlO,BruckbauerM,VoelckelW,et al.The impact of direct oral anticoagulants in traumatic brain injury patients greater than 60-years-old.Scand J Trauma Resusc Emerg Med.2018;26(1):20.
-
28
HughesPG,AlterSM,GreavesSW,et al.Acute and delayed intracranial hemorrhage in head-injured patients on warfarin versus direct oral anticoagulant therapy.J Emerg Trauma Shock.2021;14(3):123–127.
-
29
GrewalK,AtzemaCL,AustinPC,et al.Intracranial hemorrhage after head injury among older patients on anticoagulation seen in the emergency department: a population-based cohort study.CMAJ.2021;193(40):E1561–E1567.
-
30
FeeneyJM,SantoneE,DiFioriM,KisL,JayaramanV,MontgomerySC.Compared to warfarin, direct oral anticoagulants are associated with lower mortality in patients with blunt traumatic intracranial hemorrhage: a TQIP study.J Trauma Acute Care Surg.2016;81(5):843–848.
-
31
RiccardiA,SpinolaB,MinutoP,et al.小脑袋后颅内并发症injury (MHI) in patients taking vitamin K antagonists (VKA) or direct oral anticoagulants (DOACs).Am J Emerg Med.2017;35(9):1317–1319.
-
32
CiprianoA,PecoriA,BiondaAE,et al.Intracranial hemorrhage in anticoagulated patients with mild traumatic brain injury: significant differences between direct oral anticoagulants and vitamin K antagonists.Intern Emerg Med.2018;13(7):1077–1087.
-
33 ↑
ShinSS,MarshEB,AliH,NyquistPA,HanleyDF,ZiaiWC.Comparison of traumatic intracranial hemorrhage expansion and outcomes among patients on direct oral anticoagulants versus vitamin k antagonists.Neurocrit Care.2020;32(2):407–418.
-
34 ↑
WonSY,DubinskiD,BruderM,CattaniA,SeifertV,KonczallaJ.Acute subdural hematoma in patients on oral anticoagulant therapy: management and outcome.Neurosurg Focus.2017;43(5):E12.
-
35 ↑
ZeeshanM,JehanF,O’KeeffeT,et al.The novel oral anticoagulants (NOACs) have worse outcomes compared with warfarin in patients with intracranial hemorrhage after TBI.J Trauma Acute Care Surg.2018;85(5):915–920.
-
36 ↑
IvascuFA,HowellsGA,JunnFS,BairHA,BendickPJ,JanczykRJ.Rapid warfarin reversal in anticoagulated patients with traumatic intracranial hemorrhage reduces hemorrhage progression and mortality.J Trauma.2005;59(5):1131–1139.
-
37 ↑
HuttnerHB,SchellingerPD,HartmannM,et al.Hematoma growth and outcome in treated neurocritical care patients with intracerebral hemorrhage related to oral anticoagulant therapy: comparison of acute treatment strategies using vitamin K, fresh frozen plasma, and prothrombin complex concentrates.Stroke.2006;37(6):1465–1470.
-
38 ↑
SantingJAL,LeeYX,van der NaaltJ,van den BrandCL,JellemaK.Mild traumatic brain injury in elderly patients receiving direct oral anticoagulants: a systematic review and meta-analysis.J Neurotrauma.2022;39(7-8):458–472.
-
39 ↑
LeeSB,MannoEM,LaytonKF,WijdicksEF.Progression of warfarin-associated intracerebral hemorrhage after INR normalization with FFP.Neurology.2006;67(7):1272–1274.
-
40
PrestonFE,LaidlawST,SampsonB,KitchenS.Rapid reversal of oral anticoagulation with warfarin by a prothrombin complex concentrate (Beriplex): efficacy and safety in 42 patients.Br J Haematol.2002;116(3):619–624.
-
41
YasakaM,SakataT,MinematsuK,NaritomiH.Correction of INR by prothrombin complex concentrate and vitamin K in patients with warfarin related hemorrhagic complication.Thromb Res.2002;108(1):25–30.
-
42
YasakaM,SakataT,NaritomiH,MinematsuK.Optimal dose of prothrombin complex concentrate for acute reversal of oral anticoagulation.Thromb Res.2005;115(6):455–459.
-
43 ↑
RabinsteinAA,WijdicksEF.Determinants of outcome in anticoagulation-associated cerebral hematoma requiring emergency evacuation.Arch Neurol.2007;64(2):203–206.
