Microbleed prevalence and burden in anticoagulant-associated intracerebral bleed.
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ABSTRACT:
SUBMITTER: Lioutas VA
PROVIDER: S-EPMC6689674 | biostudies-literature | 2019 Aug
REPOSITORIES: biostudies-literature
Publications
Microbleed prevalence and burden in anticoagulant-associated intracerebral bleed.
Lioutas Vasileios-Arsenios VA Goyal Nitin N Katsanos Aristeidis H AH Krogias Christos C Zand Ramin R Sharma Vijay K VK Varelas Panayiotis P Malhotra Konark K Paciaroni Maurizio M Sharaf Aboubakar A Chang Jason J Kargiotis Odysseas O Pandhi Abhi A Schroeder Christoph C Tsantes Argyrios A Boviatsis Efstathios E Mehta Chandan C Mitsias Panayiotis D PD Selim Magdy H MH Alexandrov Andrei V AV Tsivgoulis Georgios G
Annals of clinical and translational neurology 20190710 8
Prior studies suggest an association between Vitamin K antagonists (VKA) and cerebral microbleeds (CMBs); less is known about nonvitamin K oral anticoagulants (NOACs). In this observational study we describe CMB profiles in a multicenter cohort of 89 anticoagulation-related intracerebral hemorrhage (ICH) patients. CMB prevalence was 51% (52% in VKA-ICH, 48% in NOAC-ICH). NOAC-ICH patients had lower median CMB count [2(IQR:1-3) vs. 7(4-11); P < 0.001]; ≥5 CMBs were less prevalent in NOAC-ICH (4% ...[more]
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Project description:The underlying pathology of cerebral microbleeds (CMBs) with mixed lobar and deep distribution remains contentious. The aim of this study was to correlate CMBs distribution to β-amyloid burden in patients with primary intracerebral hemorrhage (ICH). Fourty-seven ICH patients underwent magnetic resonance susceptibility-weighted imaging and 11C-Pittsburgh Compound B positron emission tomography. The amyloid burden was expressed as standardized uptake value ratio with reference to cerebellum, and presented as median (interquartile range). Patients were categorized into the lobar, mixed (both lobar and deep regions), and deep types of CMB. Comparing the lobar (17%), mixed (59.6%) and deep (23.4%) CMB types, the global amyloid burden was significantly higher in the mixed type than the deep type (1.10 [1.03-1.25] vs 1.00 [0.97-1.09], p = 0.011), but lower than in the lobar type (1.48 [1.18-1.50], p = 0.048). On multivariable analysis, the ratio of lobar to deep CMB number was positively correlated with global (p = 0.028) and occipital (p = 0.031) amyloid burden. In primary ICH, patients with lobar and mixed CMB types are associated with increased amyloid burden than patients with deep type. The ratio of lobar to deep CMB number is an independent indicator of cerebral β-amyloid deposition.
| S-EPMC5356186 | biostudies-literature
Project description:IntroductionDirect oral anticoagulant (DOAC)-associated intracerebral hemorrhage (ICH) is a catastrophic complication. The aim of this study was to investigate the association between computed tomography (CT)-based cerebrovascular small vessel disease (SVD) burden and DOAC-ICH as well as the DOAC concentration upon hospital admission and ICH outcome.Patients and methodsThe study included two cohorts: (1) DOAC-ICH: patients who suffered from DOAC-ICH and underwent drug level measurements upon admission; (2) DOAC-non-ICH: stable DOAC users who underwent head CT without ICH during treatment. We categorized the DOAC levels of the DOAC-ICH patients as low (<50 ng/mL), medium (50-300 ng/mL), and high (>300 ng/mL). The CT-based SVD burden (including white matter lesions [WML], lacunes, and cerebral atrophy) was evaluated, and SVD scores (range, 0-3) were used to evaluate SVD severity.ResultsA total of 43 DOAC-ICH patients and 177 DOAC-non-ICH patients were enrolled. DOAC-ICH patients were more likely to have WML, lacunes, or cerebral atrophy compared to DOAC-non-ICH patients. After adjustment, the SVD burden was associated with DOAC-ICH, with a higher risk of more severe SVD (SVD score of 2; odds ratio [OR], 10.3 [3.17, 33.3]; score of 3; OR, 16.8 [4.50, 62.6]). The proportions of patients with high, medium, and low drug levels in the DOAC-ICH group were 16.3%, 55.8%, and 27.9%, respectively. Additionally, the high-level group displayed a larger hematoma size and had worse functional outcomes at 3 months than the other two groups.Discussion and conclusionThe severity of SVD burden was associated with DOAC-ICH. Furthermore, high DOAC levels in ICH were associated with unfavorable clinical outcomes. To address the potential selection bias from these two cohorts, a prospective study to investigate the co-contribution of drug levels and SVD to DOAC-ICH is essential.
| S-EPMC10916812 | biostudies-literature
Project description:Intracerebral haemorrhage (ICH) is a life-threatening emergency, the incidence of which has increased in part due to an increase in the use of oral anticoagulants. A blood-fluid level within the haematoma, as revealed by computed tomography (CT), has been suggested as a marker for oral anticoagulant-associated ICH (OAC-ICH), but the diagnostic specificity and prognostic value of this finding remains unclear. In 855 patients with CT-confirmed acute ICH scanned within 48 h of symptom onset, we investigated the sensitivity and specificity of the presence of a CT-defined blood-fluid level (rated blinded to anticoagulant status) for identifying concomitant anticoagulant use. We also investigated the association of the presence of a blood-fluid level with six-month case fatality. Eighteen patients (2.1%) had a blood-fluid level identified on CT; of those with a blood-fluid level, 15 (83.3%) were taking anticoagulants. The specificity of blood-fluid level for OAC-ICH was 99.4%; the sensitivity was 4.2%. We could not detect an association between the presence of a blood-fluid level and an increased risk of death at six months (OR = 1.21, 95% CI 0.28-3.88, p = 0.769). The presence of a blood-fluid level should alert clinicians to the possibility of OAC-ICH, but absence of a blood-fluid level is not useful in excluding OAC-ICH.
| S-EPMC7511300 | biostudies-literature
Project description:ImportanceAlthough the use of factor Xa (FXa) inhibitors has increased substantially over the past decade, there are limited data on characteristics and outcomes of FXa inhibitor-associated intracerebral hemorrhage (ICH).ObjectiveTo investigate the association between prior oral anticoagulant use (FXa inhibitors, warfarin, or none) and in-hospital outcomes among patients with nontraumatic ICH.Design, setting, and participantsThis is a cohort study of 219 701 patients with nontraumatic ICH admitted to 1870 hospitals in the Get With The Guidelines-Stroke registry between October 2013 and May 2018. Data analysis was performed in December 2019.ExposuresAnticoagulation therapy before ICH.Main outcomes and measuresThe primary outcome was in-hospital mortality. Secondary outcomes were a composite measure of in-hospital mortality or discharge to hospice, discharge home, independent ambulation, and modified Rankin Scale (mRS) score at discharge.ResultsOf 219 701 patients (mean [SD] age, 68.2 [15.3] years; 104 940 women [47.8%]), 9202 (4.2%) were taking FXa inhibitors, 21 430 (9.8%) were taking warfarin, and 189 069 (86.0%) were not taking any oral anticoagulant before ICH. Patients taking FXa inhibitors or warfarin were older and had higher prevalence of cardiovascular risk factors. Compared with those not taking an oral anticoagulant (42 660 of 189 069 patients [22.6%]), the in-hospital mortality risk was higher for both FXa inhibitors (2487 of 9202 patients [27.0%]; adjusted odds ratio [aOR], 1.27; 95% CI, 1.20-1.34; P < .001) and warfarin (7032 of 21 430 patients [32.8%]; aOR, 1.67; 95% CI, 1.60-1.74; P < .001). Both FXa inhibitors (3478 of 9202 patients [37.8%]; aOR, 1.19; 95% CI, 1.13-1.26; P < .001) and warfarin (9151 of 21 430 patients [42.7%]; aOR, 1.50; 95% CI, 1.44-1.56; P < .001) were associated with higher odds of death or discharge to hospice compared with not taking oral anticoagulation (58 022 of 189 069 patients [30.7%]). Although the rates of discharge home, independent ambulation, mRS scores of 0 or 1, and mRS scores of 0 to 2 were numerically lower among patients taking FXa inhibitors, these differences were not significant compared with patients not taking oral anticoagulants. In contrast, patients taking FXa inhibitors were less likely to die (aOR, 0.76; 95% CI, 0.72-0.81; P < .001) or to experience death or discharge to hospice (aOR, 0.79; 95% CI, 0.75-0.84; P < .001), more likely to be discharged home (aOR, 1.18; 95% CI, 1.10-1.26; P < .001), and had better mRS scores at discharge (eg, mRS scores of 0-1: aOR, 1.24; 95% CI, 1.09-1.40; P < .001) than those treated with warfarin. Concomitant warfarin and antiplatelet therapy (either single or dual) was associated with worse outcomes compared with taking warfarin alone (eg, in-hospital mortality for dual-antiplatelet agents: aOR, 2.07; 95% CI, 1.72-2.50; P < .001). However, such incremental risk was not significant in patients taking FXa inhibitors.Conclusions and relevanceIn this cohort study, FXa inhibitor-associated ICH was associated with higher risk of mortality or death or discharge to hospice than not taking an oral anticoagulant, but patients taking FXa inhibitors had better outcomes than those with warfarin-related ICH.
| S-EPMC7887660 | biostudies-literature
Project description:ObjectiveTo determine associations between cerebral microbleed (CMB) burden with recurrent ischemic stroke (IS) and intracerebral hemorrhage (ICH) risk after IS or TIA.MethodsWe identified prospective studies of patients with IS or TIA that investigated CMBs and stroke (ICH and IS) risk during ≥3 months follow-up. Authors provided aggregate summary-level data on stroke outcomes, with CMBs categorized according to burden (single, 2-4, and ≥5 CMBs) and distribution. We calculated absolute event rates and pooled risk ratios (RR) using random-effects meta-analysis.ResultsWe included 5,068 patients from 15 studies. There were 115/1,284 (9.6%) recurrent IS events in patients with CMBs vs 212/3,781 (5.6%) in patients without CMBs (pooled RR 1.8 for CMBs vs no CMBs; 95% confidence interval [CI] 1.4-2.5). There were 49/1,142 (4.3%) ICH events in those with CMBs vs 17/2,912 (0.58%) in those without CMBs (pooled RR 6.3 for CMBs vs no CMBs; 95% CI 3.5-11.4). Increasing CMB burden increased the risk of IS (pooled RR [95% CI] 1.8 [1.0-3.1], 2.4 [1.3-4.4], and 2.7 [1.5-4.9] for 1 CMB, 2-4 CMBs, and ≥5 CMBs, respectively) and ICH (pooled RR [95% CI] 4.6 [1.9-10.7], 5.6 [2.4-13.3], and 14.1 [6.9-29.0] for 1 CMB, 2-4 CMBs, and ≥5 CMBs, respectively).ConclusionsCMBs are associated with increased stroke risk after IS or TIA. With increasing CMB burden (compared to no CMBs), the risk of ICH increases more steeply than that of IS. However, IS absolute event rates remain higher than ICH absolute event rates in all CMB burden categories.
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Project description:ObjectiveTo obtain precise estimates of age, haematoma volume, secondary haematoma expansion (HE) and mortality for patients with intracerebral haemorrhage (ICH) taking oral anticoagulants [Vitamin K antagonists (VKA-ICH) or non-Vitamin K antagonist oral anticoagulants (NOAC-ICH)] and those not taking oral anticoagulants (non-OAC ICH) at ICH symptom onset.MethodsWe conducted a systematic review and meta-analysis of studies comparing VKA-ICH or NOAC-ICH or both with non-OAC ICH. Primary outcomes were haematoma volume (in ml), HE, and mortality (in-hospital and 3-month). We calculated odds ratios (ORs) using the Mantel-Haenszel random-effects method and corresponding 95% confidence intervals (95%CI) and determined the mean ICH volume difference.ResultsWe identified 19 studies including data from 16,546 patients with VKA-ICH and 128,561 patients with non-OAC ICH. Only 2 studies reported data on 4943 patients with NOAC-ICH. Patients with VKA-ICH were significantly older than patients with non-OAC ICH (mean age difference: 5.55 years, 95%CI 4.03-7.07, p?<?0.0001, I2?=?92%, p?<?0.001). Haematoma volume was significantly larger in VKA-ICH with a mean difference of 9.66 ml (95%CI 6.24-13.07 ml, p?<?0.00001; I2?=?42%, p?=?0.05). HE occurred significantly more often in VKA-ICH (OR 2.96, 95%CI 1.74-4.97, p?<?0.00001; I2?=?65%). VKA-ICH was associated with significantly higher in-hospital mortality (VKA-ICH: 32.8% vs. non-OAC ICH: 22.4%; OR 1.83, 95%CI 1.61-2.07, p?<?0.00001, I2?=?20%, p?=?0.27) and 3-month mortality (VKA-ICH: 47.1% vs. non-OAC ICH: 25.5%; OR 2.24, 95%CI 1.52-3.31, p?<?0.00001, I2?=?71%, p?=?0.001). We did not find sufficient data for a meta-analysis comparing NOAC-ICH and non-OAC-ICH.ConclusionThis meta-analysis confirms, refines and expands findings from prior studies. We provide precise estimates of key prognostic factors and outcomes for VKA-ICH, which has larger haematoma volume, increased rate of HE and higher mortality compared to non-OAC ICH. There are insufficient data on NOACs.
| S-EPMC6851029 | biostudies-literature
Project description:ObjectiveTo compare intracerebral hemorrhage (ICH) volume and clinical outcome of non-vitamin K oral anticoagulants (NOAC)-associated ICH to warfarin-associated ICH.MethodsIn this multicenter cross-sectional observational study of patients with anticoagulant-associated ICH, consecutive patients with NOAC-ICH were compared to those with warfarin-ICH selected from a population of 344 patients with anticoagulant-associated ICH. ICH volume was measured by an observer blinded to clinical details. Outcome measures were ICH volume and clinical outcome adjusted for confounding factors.ResultsWe compared 11 patients with NOAC-ICH to 52 patients with warfarin-ICH. The median ICH volume was 2.4 mL (interquartile range [IQR] 0.3-5.4 mL) for NOAC-ICH vs 8.9 mL (IQR 4.0-21.3 mL) for warfarin-ICH (p = 0.0028). In univariate linear regression, use of warfarin (difference in cube root volume 1.61; 95% confidence interval [CI] 0.69 to 2.53) and lobar ICH location (compared with nonlobar ICH; difference in cube root volume 1.52; 95% CI 2.20 to 0.85) were associated with larger ICH volumes. In multivariable linear regression adjusting for confounding factors (sex, hypertension, previous ischemic stroke, white matter disease burden, and premorbid modified Rankin Scale score [mRS]), warfarin use remained independently associated with larger ICH (cube root) volumes (coefficient 0.64; 95% CI 0.24 to 1.25; p = 0.042). Ordered logistic regression showed an increased odds of a worse clinical outcome (as measured by discharge mRS) in warfarin-ICH compared with NOAC-ICH: odds ratio 4.46 (95% CI 1.10 to 18.14; p = 0.037).ConclusionsIn this small prospective observational study, patients with NOAC-associated ICH had smaller ICH volumes and better clinical outcomes compared with warfarin-associated ICH.
| S-EPMC4776084 | biostudies-literature
Project description:BackgroundAtrial fibrillation (AF) is associated with an increased risk of stroke. Anticoagulant (AC) therapies are effective at treating AF, but carry with them an increased risk of bleed. Research suggests that a large proportion of AF patients who have high risk of stroke and low risk of bleeding are not currently receiving AC treatment. The goal of this study was to understand the reasons why these patients do not engage in this potentially life-saving treatment.MethodThrough a self-report online survey, using validated instruments, 1,184 US adults who self-reported a diagnosis of AF were screened for the risk of stroke and bleed. Of these patients, 230 (19.4%) were at high risk of stroke, low risk of bleed, and not currently using an AC treatment, and were asked follow-up questions to assess their reasons for nontreatment, attitudes toward treatment, and attitudes toward dosing regimens.ResultsThe most common reasons patients stopped AC treatment were concerns regarding bleeding (27.8%) and other medical concerns (26.6%), whereas the most common reason cited for not being prescribed an AC in the first place was the use of antiplatelet therapy as an alternative (57.1%). In both cases, potentially erroneous decisions regarding perceived stoke and/or bleeding risk were also a factor. Finally, the largest factors regarding attitudes toward treatment and dosing regimen were instructions from an authority figure (eg, physician, pharmacist) and ease of use, respectively.ConclusionResults suggest that many AF patients who are at high risk of stroke but at low risk of bleed may not be receiving AC due to potentially inaccurate beliefs about risk. This study also found that AF patients place trust in physicians above other factors such as cost when making treatment decisions. Increased education of patients by physicians on the risks and benefits may be a simple strategy to improve outcomes.
| S-EPMC4876102 | biostudies-literature
Project description:Background and Purpose- The aim of this study was to prospectively validate our prior findings of smaller hematoma volume and lesser neurological deficit in nonvitamin K oral anticoagulant (NOAC) compared with Vitamin K antagonist (VKA)-related intracerebral hemorrhage (ICH). Methods- Prospective 12-month observational study in 15 tertiary stroke centers in the United States, Europe, and Asia. Consecutive patients with premorbid modified Rankin Scale score of <2 with acute nontraumatic anticoagulant-related ICH divided into 2 groups according to the type of anticoagulant: NOAC versus VKA. We recorded baseline ICH volume, significant hematoma expansion (absolute [12.5 mL] or relative [>33%] increase), neurological severity measured by National Institutes of Health Stroke Scale score, 90-day mortality, and functional status (modified Rankin Scale score). Results- Our cohort comprised 196 patients, 62 NOAC related (mean age, 75.0±11.4 years; 54.8% men) and 134 VKA related (mean age, 72.3±10.5; 73.1% men). There were no differences in vascular comorbidities, antiplatelet, and statin use; NOAC-related ICH patients had lower median baseline hematoma volume (13.8 [2.5-37.6] versus 19.5 [6.6-52.0] mL; P=0.026) and were less likely to have severe neurological deficits (National Institutes of Health Stroke Scale score of >10 points) on admission (37% versus 55.3%, P=0.025). VKA-ICH were more likely to have significant hematoma expansion (37.4% versus 17%, P=0.008). NOAC pretreatment was independently associated with smaller baseline hematoma volume (standardized linear regression coefficient:-0.415 [95% CI, -0.780 to -0.051]) resulting in lower likelihood of severe neurological deficit (odds ratio, 0.44; 95% CI, 0.22-0.85) in multivariable-adjusted models. Conclusions- Patients with NOAC-related ICH have smaller baseline hematoma volumes and lower odds of severe neurological deficit compared with VKA-related ICH. These findings are important for practicing clinicians making anticoagulation choices.
| S-EPMC6386175 | biostudies-literature
Project description:BackgroundCognitive impairment seems to be frequent in intracerebral hemorrhage (ICH) survivors, but remains widely understudied. In this study, we investigated the frequency and patterns of vascular cognitive disorders (VCDs) in patients with cerebral amyloid angiopathy (CAA)-related and deep ICH compared to patients with mild cognitive impairment due to Alzheimer's disease (MCI-AD) and healthy controls.MethodsWe prospectively recruited 20 patients with CAA-related lobar ICH, 20 with deep ICH, 20 with MCI-AD and 17 healthy controls. Patients with cognitive decline pre-ICH were excluded from the analysis. Each participant underwent a comprehensive neuropsychological assessment and a structural brain MRI. Cognitive assessment was performed at a median delay of 4 months after the acute phase in ICH patients, and more than 6 months after the first complaint in MCI-AD patients. Cognitive profiles were compared between groups. The prevalence of VCDs in the ICH groups was estimated using the recent VASCOG criteria.Results"Mild" and "major VCDs" were respectively observed in 87.5% and 2.5% of all ICH patients. Every patient in the CAA group had mild VCDs. No significant difference was observed in cognitive functioning between CAA-related and deep ICH patients. The most impaired process in the CAA group was naming, with a mean (±standard deviation) z-score of -5.2 ±5.5, followed by processing speed (-4.1±3.3), executive functioning (-2.6 ±2.5), memory (-2.4 ±3.5) and attention (-0.9 ±1.3). This cognitive pattern was different from the MCI-AD patients, but the groups were only different in gestural praxis, and by construction, in memory processes.ConclusionsVCDs are frequent after ICH. Cognitive patterns of patients with deep or CAA-related ICH did not differ, but there was impaired performance in specific domains distinct from the effects of Alzheimer's disease.Clinical trial registrationURL: http://www.clinicaltrials.gov. Unique identifier: NCT01619709.
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