ImportanceInternational guidelines recommend avoiding intravenous thrombolysis (IVT) in patients with ischemic stroke who have a recent intake of a direct oral anticoagulant (DOAC).ObjectiveTo determine the risk of symptomatic intracranial hemorrhage (sICH) associated with use of IVT in patients with recent DOAC ingestion.Design, Setting, and ParticipantsThis international, multicenter, retrospective cohort study included 64 primary and comprehensive stroke centers across Europe, Asia, Australia, and New Zealand. Consecutive adult patients with ischemic stroke who received IVT (both with and without thrombectomy) were included. Patients whose last known DOAC ingestion was more than 48 hours before stroke onset were excluded. A total of 832 patients with recent DOAC use were compared with 32 375 controls without recent DOAC use. Data were collected from January 2008 to December 2021.ExposuresPrior DOAC therapy (confirmed last ingestion within 48 hours prior to IVT) compared with no prior oral anticoagulation.Main Outcomes and MeasuresThe main outcome was sICH within 36 hours after IVT, defined as worsening of at least 4 points on the National Institutes of Health Stroke Scale and attributed to radiologically evident intracranial hemorrhage. Outcomes were compared according to different selection strategies (DOAC-level measurements, DOAC reversal treatment, IVT with neither DOAC-level measurement nor idarucizumab). The association of sICH with DOAC plasma levels and very recent ingestions was explored in sensitivity analyses.ResultsOf 33 207 included patients, 14 458 (43.5%) were female, and the median (IQR) age was 73 (62-80) years. The median (IQR) National Institutes of Health Stroke Scale score was 9 (5-16). Of the 832 patients taking DOAC, 252 (30.3%) received DOAC reversal before IVT (all idarucizumab), 225 (27.0%) had DOAC-level measurements, and 355 (42.7%) received IVT without measuring DOAC plasma levels or reversal treatment. The unadjusted rate of sICH was 2.5% (95% CI, 1.6-3.8) in patients taking DOACs compared with 4.1% (95% CI, 3.9-4.4) in control patients using no anticoagulants. Recent DOAC ingestion was associated with lower odds of sICH after IVT compared with no anticoagulation (adjusted odds ratio, 0.57; 95% CI, 0.36-0.92). This finding was consistent among the different selection strategies and in sensitivity analyses of patients with detectable plasma levels or very recent ingestion.Conclusions and RelevanceIn this study, there was insufficient evidence of excess harm associated with off-label IVT in selected patients after ischemic stroke with recent DOAC ingestion.
Background and Objectives:Declines in stroke admission, intravenous thrombolysis, and mechanical thrombectomy volumes were reported during the first wave of the COVID-19 pandemic. There is a paucity of data on the longer-term effect of the pandemic on stroke volumes over the course of a year and through the second wave of the pandemic. We sought to measure the impact of the COVID-19 pandemic on the volumes of stroke admissions, intracranial hemorrhage (ICH), intravenous thrombolysis (IVT), and mechanical thrombectomy over a one-year period at the onset of the pandemic (March 1, 2020, to February 28, 2021) compared with the immediately preceding year (March 1, 2019, to February 29, 2020).Methods:We conducted a longitudinal retrospective study across 6 continents, 56 countries, and 275 stroke centers. We collected volume data for COVID-19 admissions and 4 stroke metrics: ischemic stroke admissions, ICH admissions, intravenous thrombolysis treatments, and mechanical thrombectomy procedures. Diagnoses were identified by their ICD-10 codes or classifications in stroke databases.Results:There were 148,895 stroke admissions in the one-year immediately before compared to 138,453 admissions during the one-year pandemic, representing a 7% decline (95% confidence interval [95% CI 7.1, 6.9]; p<0.0001). ICH volumes declined from 29,585 to 28,156 (4.8%, [5.1, 4.6]; p<0.0001) and IVT volume from 24,584 to 23,077 (6.1%, [6.4, 5.8]; p<0.0001). Larger declines were observed at high volume compared to low volume centers (all p<0.0001). There was no significant change in mechanical thrombectomy volumes (0.7%, [0.6,0.9]; p=0.49). Stroke was diagnosed in 1.3% [1.31,1.38] of 406,792 COVID-19 hospitalizations. SARS-CoV-2 infection was present in 2.9% ([2.82,2.97], 5,656/195,539) of all stroke hospitalizations.Discussion:There was a global decline and shift to lower volume centers of stroke admission volumes, ICH volumes, and IVT volumes during the 1st year of the COVID-19 pandemic compared to the prior year. Mechanical thrombectomy volumes were preserved. These results suggest preservation in the stroke care of higher severity of disease through the first pandemic year.Trial Registration Information:This study is registered underNCT04934020.
Background and Purpose: It is believed that stroke occurring due to posterior circulation large vessel occlusion (PCLVO) and that occurring due to anterior circulation large vessel occlusion (ACLVO) differ in terms of their pathophysiology and the outcome of their acute management in relation to endovascular mechanical thrombectomy (MT). Limited sample size and few randomized controlled trials (RCTs) with respect to PCLVO make the safety and efficacy of MT, which has been confirmed in ACLVO, difficult to assess in the posterior circulation. We therefore conducted a meta-analysis to study to which extent MT in PCLVO differs from ACLVO.Materials and Methods: We searched the databases PubMed, Cochrane, and EMBASE for studies published between 2010 and January 2021, with information on risk factors, safety, and efficacy outcomes of MT in PCLVO vs. ACLVO and conducted a systematic review and meta-analysis; we compared baseline characteristics, reperfusion treatment profiles [including rates of intravenous thrombolysis (IVT) and onset-to-IVT and onset-to-groin puncture times], recanalization success [Thrombolysis In Cerebral Infarction scale (TICI) 2b/3], symptomatic intracranial hemorrhage (sICH), and favorable functional outcome [modified Rankin Score (mRS) 0–2] and mortality at 90 days.Results: Sixteen studies with MT PCLVO (1,172 patients) and ACLVO (7,726 patients) were obtained from the search. The pooled estimates showed higher baseline National Institutes of Health Stroke Scale (NIHSS) score (SMD 0.32, 95% CI 0.15–0.48) in the PCLVO group. PCLVO patients received less often IVT (OR 0.65, 95% CI 0.53–0.79). Onset-to-IVT time (SMD 0.86, 95% CI 0.45–1.26) and onset-to-groin puncture time (SMD 0.59, 95% CI 0.33–0.85) were longer in the PCLVO group. The likelihood of obtaining successful recanalization and favorable functional outcome at 90 days was comparable between the two groups. PCLVO was, however, associated with less sICH (OR 0.56, 95% CI 0.37–0.85) but higher mortality (OR 1.92, 95% CI 1.46–2.53).Conclusions: This meta-analysis indicates that MT in PCLVO may be comparably efficient in obtaining successful recanalization and 90 day favorable functional outcome just as in ACLVO. Less sICH in MT-treated PCLVO patients might be the result of the lower IVT rate in this group. Higher baseline NIHSS and longer onset-to-IVT and onset-to-groin puncture times may have contributed to a higher 90 day mortality in PCLVO patients.
Sialic acids as the terminal caps of the cellular glycocalyx play an essential role in self-recognition and were shown to modulate complement processes via interaction between α2,3-linked sialic acids and complement factor H. Previously, it was suggested that low molecular weight α2,8-linked polysialic acid (polySia avDP20) interferes with complement activation, but the exact molecular mechanism is still unclear. Here, we show that soluble polySia avDP20 (molecular weight of ~ 6 kDa) reduced the binding of serum-derived alternative pathway complement activator properdin to the cell surface of lesioned Hepa-1c1c7 and PC-12 neuroblastoma cells. Furthermore, polySia avDP20 added to human serum blocked the alternative complement pathway triggered by plate-bound lipopolysaccharides. Interestingly, no inhibitory effect was observed with monosialic acid or oligosialic acid with a chain length of DP3 and DP5. In addition, polySia avDP20 directly bound properdin, but not complement factor H. These data show that soluble polySia avDP20 binds properdin and reduces the alternative complement pathway activity. Results strengthen the previously described concept of self-recognition of sialylation as check-point control of complement activation in innate immunity.
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