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1.
JAMA Neurol ; 78(11): 1314-1323, 2021 11 01.
Article in English | MEDLINE | ID: covidwho-1439655

ABSTRACT

Importance: Thrombosis with thrombocytopenia syndrome (TTS) has been reported after vaccination with the SARS-CoV-2 vaccines ChAdOx1 nCov-19 (Oxford-AstraZeneca) and Ad26.COV2.S (Janssen/Johnson & Johnson). Objective: To describe the clinical characteristics and outcome of patients with cerebral venous sinus thrombosis (CVST) after SARS-CoV-2 vaccination with and without TTS. Design, Setting, and Participants: This cohort study used data from an international registry of consecutive patients with CVST within 28 days of SARS-CoV-2 vaccination included between March 29 and June 18, 2021, from 81 hospitals in 19 countries. For reference, data from patients with CVST between 2015 and 2018 were derived from an existing international registry. Clinical characteristics and mortality rate were described for adults with (1) CVST in the setting of SARS-CoV-2 vaccine-induced immune thrombotic thrombocytopenia, (2) CVST after SARS-CoV-2 vaccination not fulling criteria for TTS, and (3) CVST unrelated to SARS-CoV-2 vaccination. Exposures: Patients were classified as having TTS if they had new-onset thrombocytopenia without recent exposure to heparin, in accordance with the Brighton Collaboration interim criteria. Main Outcomes and Measures: Clinical characteristics and mortality rate. Results: Of 116 patients with postvaccination CVST, 78 (67.2%) had TTS, of whom 76 had been vaccinated with ChAdOx1 nCov-19; 38 (32.8%) had no indication of TTS. The control group included 207 patients with CVST before the COVID-19 pandemic. A total of 63 of 78 (81%), 30 of 38 (79%), and 145 of 207 (70.0%) patients, respectively, were female, and the mean (SD) age was 45 (14), 55 (20), and 42 (16) years, respectively. Concomitant thromboembolism occurred in 25 of 70 patients (36%) in the TTS group, 2 of 35 (6%) in the no TTS group, and 10 of 206 (4.9%) in the control group, and in-hospital mortality rates were 47% (36 of 76; 95% CI, 37-58), 5% (2 of 37; 95% CI, 1-18), and 3.9% (8 of 207; 95% CI, 2.0-7.4), respectively. The mortality rate was 61% (14 of 23) among patients in the TTS group diagnosed before the condition garnered attention in the scientific community and 42% (22 of 53) among patients diagnosed later. Conclusions and Relevance: In this cohort study of patients with CVST, a distinct clinical profile and high mortality rate was observed in patients meeting criteria for TTS after SARS-CoV-2 vaccination.


Subject(s)
COVID-19 Vaccines/therapeutic use , Drug-Related Side Effects and Adverse Reactions/mortality , Registries , Sinus Thrombosis, Intracranial/mortality , Thrombocytopenia/mortality , Venous Thromboembolism/mortality , Ad26COVS1 , Adult , Aged , BNT162 Vaccine , COVID-19 Vaccines/adverse effects , ChAdOx1 nCoV-19 , Cohort Studies , Female , Hospital Mortality , Humans , Male , Middle Aged , Outcome Assessment, Health Care , Sex Factors , Sinus Thrombosis, Intracranial/blood , Sinus Thrombosis, Intracranial/chemically induced , Syndrome , Thrombocytopenia/blood , Thrombocytopenia/chemically induced , Venous Thromboembolism/blood , Venous Thromboembolism/chemically induced , Young Adult
2.
JAMA ; 326(4): 332-338, 2021 07 27.
Article in English | MEDLINE | ID: covidwho-1355843

ABSTRACT

Importance: Cases of cerebral venous sinus thrombosis in combination with thrombocytopenia have recently been reported within 4 to 28 days of vaccination with the ChAdOx1 nCov-19 (AstraZeneca/Oxford) and Ad.26.COV2.S (Janssen/Johnson & Johnson) COVID-19 vaccines. An immune-mediated response associated with platelet factor 4/heparin antibodies has been proposed as the underlying pathomechanism. Objective: To determine the frequencies of admission thrombocytopenia, heparin-induced thrombocytopenia, and presence of platelet factor 4/heparin antibodies in patients diagnosed with cerebral venous sinus thrombosis prior to the COVID-19 pandemic. Design, Setting, and Participants: This was a descriptive analysis of a retrospective sample of consecutive patients diagnosed with cerebral venous sinus thrombosis between January 1987 and March 2018 from 7 hospitals participating in the International Cerebral Venous Sinus Thrombosis Consortium from Finland, the Netherlands, Switzerland, Sweden, Mexico, Iran, and Costa Rica. Of 952 patients, 865 with available baseline platelet count were included. In a subset of 93 patients, frozen plasma samples collected during a previous study between September 2009 and February 2016 were analyzed for the presence of platelet factor 4/heparin antibodies. Exposures: Diagnosis of cerebral venous sinus thrombosis. Main Outcomes and Measures: Frequencies of admission thrombocytopenia (platelet count <150 ×103/µL), heparin-induced thrombocytopenia (as diagnosed by the treating physician), and platelet factor 4/heparin IgG antibodies (optical density >0.4, in a subset of patients with previously collected plasma samples). Results: Of 865 patients (median age, 40 years [interquartile range, 29-53 years], 70% women), 73 (8.4%; 95% CI, 6.8%-10.5%) had thrombocytopenia, which was mild (100-149 ×103/µL) in 52 (6.0%), moderate (50-99 ×103/µL) in 17 (2.0%), and severe (<50 ×103/µL) in 4 (0.5%). Heparin-induced thrombocytopenia with platelet factor 4/heparin antibodies was diagnosed in a single patient (0.1%; 95% CI, <0.1%-0.7%). Of the convenience sample of 93 patients with cerebral venous sinus thrombosis included in the laboratory analysis, 8 (9%) had thrombocytopenia, and none (95% CI, 0%-4%) had platelet factor 4/heparin antibodies. Conclusions and Relevance: In patients with cerebral venous sinus thrombosis prior to the COVID-19 pandemic, baseline thrombocytopenia was uncommon, and heparin-induced thrombocytopenia and platelet factor 4/heparin antibodies were rare. These findings may inform investigations of the possible association between the ChAdOx1 nCoV-19 and Ad26.COV2.S COVID-19 vaccines and cerebral venous sinus thrombosis with thrombocytopenia.


Subject(s)
COVID-19 Vaccines/adverse effects , Heparin/immunology , Platelet Factor 4/immunology , Sinus Thrombosis, Intracranial/complications , Thrombocytopenia/etiology , Adult , Antibodies/blood , Female , Heparin/adverse effects , Humans , Male , Middle Aged , Retrospective Studies , Sinus Thrombosis, Intracranial/immunology , Thrombocytopenia/epidemiology
3.
J Stroke Cerebrovasc Dis ; 30(9): 105985, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1294009

ABSTRACT

OBJECTIVES: COVID-19 pandemic has forced important changes in health care worldwide. Stroke care networks have been affected, especially during peak periods. We assessed the impact of the pandemic and lockdowns in stroke admissions and care in Latin America. MATERIALS AND METHODS: A multinational study (7 countries, 18 centers) of patients admitted during the pandemic outbreak (March-June 2020). Comparisons were made with the same period in 2019. Numbers of cases, stroke etiology and severity, acute care and hospitalization outcomes were assessed. RESULTS: Most countries reported mild decreases in stroke admissions compared to the same period of 2019 (1187 vs. 1166, p = 0.03). Among stroke subtypes, there was a reduction in ischemic strokes (IS) admissions (78.3% vs. 73.9%, p = 0.01) compared with 2019, especially in IS with NIHSS 0-5 (50.1% vs. 44.9%, p = 0.03). A substantial increase in the proportion of stroke admissions beyond 48 h from symptoms onset was observed (13.8% vs. 20.5%, p < 0.001). Nevertheless, no differences in total reperfusion treatment rates were observed, with similar door-to-needle, door-to-CT, and door-to-groin times in both periods. Other stroke outcomes, as all-type mortality during hospitalization (4.9% vs. 9.7%, p < 0.001), length of stay (IQR 1-5 days vs. 0-9 days, p < 0.001), and likelihood to be discharged home (91.6% vs. 83.0%, p < 0.001), were compromised during COVID-19 lockdown period. CONCLUSIONS: In this Latin America survey, there was a mild decrease in admissions of IS during the COVID-19 lockdown period, with a significant delay in time to consultations and worse hospitalization outcomes.


Subject(s)
COVID-19/prevention & control , Endovascular Procedures/trends , Hospitalization/trends , Practice Patterns, Physicians'/trends , Stroke/therapy , Time-to-Treatment/trends , COVID-19/transmission , Cause of Death/trends , Endovascular Procedures/adverse effects , Endovascular Procedures/mortality , Female , Health Care Surveys , Hospital Mortality/trends , Humans , Latin America , Length of Stay/trends , Male , Patient Admission/trends , Patient Discharge/trends , Stroke/diagnosis , Stroke/mortality , Time Factors , Treatment Outcome
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