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.

Objective.To collect information on frequency of pregnancy and delivery complications in Charcot-Marie-Tooth (CMT) and on CMT course during pregnancy.Methods.Through an ad hoc online questionnaire, we investigated pregnancy and neuropathy course in CMT women adhering to the Italian CMT Registry. Data were compared to controls (recruited among friends and unaffected relatives) and the Italian (or other reference) population.Results.We collected data on 193 pregnancies from 86 CMT women (aged 20-73 years), with 157 deliveries (81.4%) after a mean of 38.6 gestational weeks. In CMT women there were no differences with controls (59 pregnancies and 46 deliveries from 24 controls) and the reference population for: miscarriages (11.4%), planned (21.0%) and emergency (14.0%) cesarean sections. We found a significantly higher frequency of placenta previa (1.6% vs 0.4%), abnormal fetal presentations (8.4% vs 4.5%), and preterm deliveries (20.3% vs 6.9%; most in the 34-36 week of gestation range) as compared to reference populations. Excluding twins, newborn weight did not differ from the reference population. Post-partum bleeding rate in CMT patients (2.1%) was similar to the general population (2.4%). CMT status worsened during 18/193 pregnancies (9.3%) with no recovery in 16 of them and similar figures in CMT1A as compared to non-CMT1A subtypes.Conclusions.We observed higher rates of placenta previa, abnormal presentations, and preterm deliveries in CMT, but pregnancy outcome and newborn weight and health were similar to the reference populations. Worsening of CMT is not infrequent and occurs not only in CMT1A. Pregnant CMT women should be monitored with particular care.

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