Intracerebral hemorrhage (ICH) is the most devastating adverse event in patients receiving oral anticoagulation. There is only sparse evidence regarding ICH related to the use of non-vitamin K ...antagonist oral anticoagulant (NOAC) agents.
To evaluate the early clinical and radiological course, acute management, and outcome of ICH related to NOAC use.
Prospective investigator-initiated, multicenter observational study. All diagnostic and treatment decisions, including administration of hemostatic factors (eg, prothrombin complex concentrate), were left to the discretion of the treating physicians. The setting was 38 stroke units across Germany (February 1, 2012, to December 31, 2014). The study included 61 consecutive patients with nontraumatic NOAC-associated ICH, of whom 45 (74%) qualified for the hematoma expansion analysis.
Hematoma expansion, intraventricular hemorrhage, and reversal of anticoagulation during the acute phase. Recorded were the 3-month functional outcome, factors associated with an unfavorable outcome (modified Rankin Scale score, 3-6), any new intraventricular extension or an increase in the modified Graeb score by at least 2 points, and the frequency of substantial hematoma expansion (defined as relative ≥ 33% or absolute ≥ 6-mL volume increase).
In total, 41% (25 of 61) of patients with NOAC-associated ICH were female, and the mean (SD) patient age was 76.1 (11.6) years. At admission, the median National Institutes of Health Stroke Scale score was 10 (interquartile range, 4-18). The mean (SD) baseline hematoma volume was 23.7 (31.3) mL. In patients with sequential imaging for the hematoma expansion analysis, substantial hematoma expansion occurred in 38% (17 of 45). New or increased intraventricular hemorrhage was observed in 18% (8 of 45). Overall mortality was 28% (17 of 60 follow-up data were missing in 1 patient) at 3 months, and 65% (28 of 43) of survivors had an unfavorable outcome (modified Rankin Scale score, 3-6). Overall, 57% (35 of 61) of the patients received prothrombin complex concentrate, with no statistically significant effect on the frequency of substantial hematoma expansion (43% 12 of 28 for prothrombin complex concentrate vs 29% 5 of 17 for no prothrombin complex concentrate, P = .53), or on the occurrence of an unfavorable outcome (modified Rankin Scale score, 3-6) (odds ratio, 1.20; 95% CI, 0.37-3.87; P = .76).
Non-vitamin K antagonist oral anticoagulant-associated ICH has a high mortality and an unfavorable outcome, and hematoma expansion is frequent. Larger-scale prospective studies are needed to determine whether the early administration of specific antidotes can improve the poor prognosis of NOAC-associated ICH.
Cardioembolism in paroxysmal atrial fibrillation (pxAF) is a frequent cause of ischemic stroke. Sensitive detection of pxAF after stroke is crucial for adequate secondary stroke prevention; the ...optimal diagnostic modality to detect pxAF on stroke units is unknown. We compared 24-hour Holter electrocardiography (ECG) with continuous stroke unit ECG monitoring (CEM) for pxAF detection.
Patients with acute ischemic stroke or transient ischemic attack were prospectively enrolled. After a 12-channel ECG on admission, all patients received 24-hour Holter ECG and CEM. Additionally, ECG monitoring data underwent automated analysis using dedicated software to identify pxAF. Patients with a history of atrial fibrillation or with atrial fibrillation on the admission ECG were excluded.
Four hundred ninety-six patients (median age, 69 years; 61.5% male) fulfilled all inclusion criteria (ischemic stroke: 80.4%; transient ischemic attack: 19.6%). Median stroke unit stay lasted 88.8 hours (interquartile range, 65.0-122.0). ECG data for automated CEM analysis were available for a median time of 64.0 hours (43.0-89.8). Paroxysmal AF was documented in 41 of 496 patients (8.3%). Of these, Holter detected pxAF in 34.1%; CEM in 65.9%; and automated CEM in 92.7%. CEM and automated CEM detected significantly more patients with pxAF than Holter (P<0.001), and automated CEM detected more patients than CEM (P<0.001).
Automated analysis of CEM improves pxAF detection in patients with stroke on stroke units compared with 24-hour Holter ECG. The comparative usefulness of prolonged or repetitive Holter ECG recordings requires further evaluation.
Plasma concentrations of direct oral anticoagulants (DOACs) vary largely between individuals, and they correlate well with desired and adverse outcomes. Although regular concentration monitoring of ...DOACs is not recommended, information on DOAC exposure could be useful in situations when multiple DOAC-clearance pathways are impaired or nonadherence is suspected. Self-sampling techniques, like the use of dried-blood spots (DBSs), would be particularly useful because they enable the collection of information in ambulatory patients at relevant points in time of the dosing interval (e.g., trough). We developed and validated a DBS-based assay to quantify all currently marketed DOACs (apixaban, dabigatran, edoxaban, and rivaroxaban) in a single ultraperformance-liquid-chromatography–tandem-mass-spectrometry assay. It fulfilled all validation standards within a hematocrit range of 0.33–0.65 and was linear over the calibration ranges of 2.5–750 ng/mL (apixaban and rivaroxaban), 4.4–750 ng/mL (dabigatran), and 9.3–750 ng/mL (edoxaban). Only minor ion suppression (matrix effect ≤13%) was present, inter- and intra-assay precision was ≤13%, and inter- and intra-assay accuracies ranged between 88 and 110%. All DOACs were stable in DBSs up to 52 days at room temperature, if the DBSs were protected from light and humidity. The correlation between (whole blood) DBS and plasma concentrations was assessed in 33 patients under regular DOAC therapy. Deming-regression coefficients between simultaneously collected capillary DBSs and plasma samples were used to predict plasma concentrations from DBSs. Bland–Altman plots revealed a strong agreement between predicted and observed plasma concentrations, thus confirming the suitability of DBSs for DOAC monitoring as an important step toward the important aim of self-sampling at home.
Whether newly diagnosed atrial fibrillation (nAF) after stroke reflects underlying heart disease and represents an increased risk of cardioembolic stroke, or whether it is triggered by neurogenic ...mechanisms remains uncertain. We investigated, whether cardiovascular risk factors and echocardiographic parameters in patients with nAF are similar to patients with known AF (kAF) and differ from patients without AF.
Consecutive acute ischemic stroke patients were enrolled into a prospective stroke database. All patients with echocardiography were included and univariable and multivariable testing was applied to compare clinical characteristics and echocardiographic findings among patients with nAF, kAF, and no AF.
A total of 1397 patients were included (male, 62.3%; median age, 71 years). AF was present in 320 (22.9%) patients. Of those, nAF was present in 36.2% (116/320) and kAF in 63.8% (204/320). No clinical or echocardiographic factor was independently associated with detection of nAF compared with kAF but a trend toward larger left atrial diameters in patients with kAF was observed (P=0.070). In contrast, patients with nAF were more often female (P<0.001), older (P<0.001) and had a larger left atrial diameters (P<0.001) compared with patients without AF. While stroke severity in patients with nAF and kAF was similar, patients without AF had less severe strokes.
Stroke patients with nAF and with kAF share common cardiovascular risk factors, have similar echocardiographic findings and suffer equally severe strokes. We conclude that preexisting heart disease is the major cause of AF that is first diagnosed after stroke.
Purpose
Patients with glioblastoma (GBM) or brain metastases (MET) and atrial fibrillation (AF) might be at an increased risk of intracranial hemorrhage (ICH) due to anticoagulation (AC). Our aim was ...to assess this risk.
Methods
Our institution’s database (from 2005 to 2017) was screened for patients with GBM or MET and AF with an indication for AC according to their CHA
2
DS
2
VASc stroke risk score (≥ 2). Required follow-up was at least 3 months. AC was either performed with heparins, phenprocoumon or non-Vitamin K antagonist oral anticoagulants. Applying the propensity score approach, patient cohorts (matched according to primary tumor, age, sex) were generated (GBM or MET with AF ± AC, GBM or MET without AF/AC, no GBM or MET but AF on AC). ICH was defined as clinical deterioration caused by new blood on imaging. A log rank test was performed to compare the risk for ICH between the three groups.
Results
In total, 104 patients were identified of which 49 with GBM (37% on AC) and 37 with MET (46% on AC) were successfully matched. Median follow up was 8.6 and 7.2 months, respectively. ICH occurred in 10.2% of GBM + AF and 12.2% GBM-AF, whereas 8% of patients with AF on AC suffered ICH (p = 0.076). 13.5% of patients with MET + AF had ICHs, in the controls it was 16% for MET-AF and 8% for AF on AC (p = 0.11).
Conclusion
AC did not seem to influence the incidence of ICH in patients with glioblastoma or brain metastases within follow up of just under 9 months.
Objective
Whether intracerebral hemorrhage (ICH) associated with non–vitamin K antagonist oral anticoagulants (NOAC‐ICH) has a better outcome compared to ICH associated with vitamin K antagonists ...(VKA‐ICH) is uncertain.
Methods
We performed a systematic review and individual patient data meta‐analysis of cohort studies comparing clinical and radiological outcomes between NOAC‐ICH and VKA‐ICH patients. The primary outcome measure was 30‐day all‐cause mortality. All outcomes were assessed in multivariate regression analyses adjusted for age, sex, ICH location, and intraventricular hemorrhage extension.
Results
We included 7 eligible studies comprising 219 NOAC‐ICH and 831 VKA‐ICH patients (mean age = 77 years, 52.5% females). The 30‐day mortality was similar between NOAC‐ICH and VKA‐ICH (24.3% vs 26.5%; hazard ratio = 0.94, 95% confidence interval CI = 0.67–1.31). However, in multivariate analyses adjusting for potential confounders, NOAC‐ICH was associated with lower admission National Institutes of Health Stroke Scale (NIHSS) score (linear regression coefficient = −2.83, 95% CI = −5.28 to −0.38), lower likelihood of severe stroke (NIHSS > 10 points) on admission (odds ratio OR = 0.50, 95% CI = 0.30–0.84), and smaller baseline hematoma volume (linear regression coefficient = −0.24, 95% CI = −0.47 to −0.16). The two groups did not differ in the likelihood of baseline hematoma volume < 30cm3 (OR = 1.14, 95% CI = 0.81–1.62), hematoma expansion (OR = 0.97, 95% CI = 0.63–1.48), in‐hospital mortality (OR = 0.73, 95% CI = 0.49–1.11), functional status at discharge (common OR = 0.78, 95% CI = 0.57–1.07), or functional status at 3 months (common OR = 1.03, 95% CI = 0.75–1.43).
Interpretation
Although functional outcome at discharge, 1 month, or 3 months was comparable after NOAC‐ICH and VKA‐ICH, patients with NOAC‐ICH had smaller baseline hematoma volumes and less severe acute stroke syndromes. Ann Neurol 2018;84:702–712
Patients treated with oral anticoagulants (OAC) carry a 7- to 10-fold higher risk of intracerebral hemorrhage (ICH) than patients without OAC. ICH related to oral anticoagulation (OAC-ICH) is a ...particularly severe form of stroke. The overall incidence of OAC-ICH ranges between 2 and 9 per 100,000 population/year and is expected to increase as the number of patients treated with OAC rises. Besides common risk factors of ICH such as age and hypertension, the intensity of anticoagulation, previous ischemic stroke, and the presence of cerebral vasculopathies (e.g., amyloid angiopathy, subcortical hypertensive arteriopathy) are associated with a greater risk of OAC-ICH. Mortality rates in OAC-ICH of 52 to 67% considerably exceed those of ICH in nonanticoagulated patients. Factors that mediate worse outcome in OAC-ICH are more frequent and prolonged secondary hematoma enlargement and intraventricular hemorrhage, The current concept of emergency treatment in OAC-ICH is rapid restoration of effective coagulation using hemostatic factors such as prothrombin complex concentrate, fresh frozen plasma, factor IX concentrates, and recombinant factor VIIa in addition to vitamin K. Emergency management of ICH under treatment with the new direct OAC is a major challenge. In the absence of specific antidotes, prothrombin concentrates are recommended mainly on the basis of preclinical data.
Background and Purpose:
Clinical outcome and mortality after endovascular thrombectomy (EVT) in patients with ischemic stroke are commonly assessed after 3 months. In patients with acute kidney ...injury (AKI), unfavorable results for 3-month mortality have been reported. However, data on the in-hospital mortality after EVT in this population are sparse. In the present study, we assessed whether AKI impacts in-hospital and 3-month mortality in patients undergoing EVT.
Materials and Methods:
From a prospectively recruiting database, consecutive acute ischemic stroke patients receiving EVT between 2010 and 2018 due to acute large vessel occlusion were included. Post-contrast AKI (PC-AKI) was defined as an increase of baseline creatinine of ≥0.5 mg/dL or >25% within 48 h after the first measurement at admission. Adjusting for potential confounders, associations between PC-AKI and mortality after stroke were tested in univariate and multivariate logistic regression models.
Results:
One thousand one hundred sixty-nine patients were included; 166 of them (14.2%) died during the acute hospital stay. Criteria for PC-AKI were met by 29 patients (2.5%). Presence of PC-AKI was associated with a significantly higher risk of in-hospital mortality in multivariate analysis odds ratio (OR) = 2.87, 95% confidence interval (CI) = 1.16–7.13,
p
= 0.023. Furthermore, factors associated with in-hospital mortality encompassed higher age (OR = 1.03, 95% CI = 1.01–1.04,
p
= 0.002), stroke severity (OR = 1.05, 95% CI = 1.03–1.08,
p
< 0.001), symptomatic intracerebral hemorrhage (OR = 3.20, 95% CI = 1.69–6.04,
p
< 0.001), posterior circulation stroke (OR = 2.85, 95% CI = 1.72–4.71,
p
< 0.001), and failed recanalization (OR = 2.00, 95% CI = 1.35–3.00,
p
= 0.001).
Conclusion:
PC-AKI is rare after EVT but represents an important risk factor for in-hospital mortality and for mortality within 3 months after hospital discharge. Preventing PC-AKI after EVT may represent an important and potentially lifesaving effort in future daily clinical practice.
In patients who present with acute ischemic stroke while on treatment with non-vitamin K antagonist oral anticoagulants (NOACs), coagulation testing is necessary to confirm the eligibility for ...thrombolytic therapy. We evaluated the current use of coagulation testing in routine clinical practice in patients who were on NOAC treatment at the time of acute ischemic stroke.
Prospective multicenter observational RASUNOA registry (Registry of Acute Stroke Under New Oral Anticoagulants; February 2012-2015). Results of locally performed nonspecific (international normalized ratio, activated partial thromboplastin time, and thrombin time) and specific (antifactor Xa tests, hemoclot assay) coagulation tests were documented. The implications of test results for thrombolysis decision-making were explored.
In the 290 patients enrolled, nonspecific coagulation tests were performed in ≥95% and specific coagulation tests in 26.9% of patients. Normal values of activated partial thromboplastin time and international normalized ratio did not reliably rule out peak drug levels at the time of the diagnostic tests (false-negative rates 11%-44% 95% confidence interval 1%-69%). Twelve percent of patients apparently failed to take the prescribed NOAC prior to the acute event. Only 5.7% (9/159) of patients in the 4.5-hour time window received thrombolysis, and NOAC treatment was documented as main reason for not administering thrombolysis in 52.7% (79/150) of patients.
NOAC treatment currently poses a significant barrier to thrombolysis in ischemic stroke. Because nonspecific coagulation test results within normal range have a high false-negative rate for detection of relevant drug concentrations, rapid drug-specific tests for thrombolysis decision-making should be established.
URL: http://www.clinicaltrials.gov. Unique identifier: NCT01850797.
High infection rate after severe stroke may partly relate to brain-induced immunodepression syndrome. However, the underlying pathophysiology remains unclear. The aim of the current study was to ...investigate the role of autonomic shift in increased susceptibility to infection after acute intracerebral hemorrhage (ICH).
We retrospectively analyzed 62 selected patients with acute ICH from our prospective database. Autonomic shift was assessed using the cross-correlational baroreflex sensitivity (BRS). The occurrence and cause of in-hospital infections were assessed based on the clinical and laboratory courses. Demographic and clinical data including initial stroke severity, hemorrhage volume, intraventricular blood extension, history of aspiration, and invasive procedures such as mechanical ventilation, surgical hematoma evacuation, external ventricular drainage, central venous and urinary catheters, and nasogastric feeding were recorded and included in the analysis.
We identified 36 (58%) patients with infection during the first 5 days of hospital stay. Patients with infections had significantly lower BRS, higher initial NIHSS scores, larger hemorrhages, and more frequently had intraventricular blood extension and underwent invasive procedures. In the multivariate regression model, decreased BRS (OR, 0.54; 95% CI, 0.32-0.91; P=0.02) and invasive procedures (OR, 2.32; 95% CI, 1.5-3.6; P<0.001) remained independent predictors for an infection after ICH.
Decreased BRS was independently associated with infections after ICH. Autonomic shift may play an important role in increased susceptibility to infections after acute brain injury including ICH. The possible therapeutic relevance of autonomic modulation warrants further studies.
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