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2.
Am J Case Rep ; 22: e933397, 2021 Sep 03.
Article in English | MEDLINE | ID: covidwho-1395310

ABSTRACT

BACKGROUND Multiple vaccines have been developed against COVID-19 as a collaborative worldwide effort. On March 18, 2021 the European Medicines Agency reported a serious and rare adverse effect of thrombosis with thrombocytopenia syndrome (TTS) after receiving the ChAdOx1 nCoV-19 vaccine; most of these cases were associated with cerebral venous sinus thrombosis (CVST). To date, there are no cases of TTS-related CVST reported after receipt of either of the 2 mRNA COVID-19 vaccines authorized for use in the United States. We report a case of CVST with the Moderna mRNA vaccine. CASE REPORT A healthy 45-year-old male patient without any risk factors presented with new-onset seizures 8 days after the receipt of the 2nd dose of Moderna (mRNA-1273), with concomitant SAH as a complication. One day prior to admission, he noted headaches and neck pain unrelieved by over-the-counter analgesics. Computed tomography (CT) scan brain without contrast revealed a left frontal lobe intracerebral hemorrhage (ICH) along with subarachnoid hemorrhage (SAH). A subsequent contrast-enhanced magnetic resonance imaging (MRI) brain confirmed the CT findings as well as anterior superior sagittal sinus thrombosis. He had normal platelet count with a negative thrombophilia work-up and cancer screening. He was successfully anticoagulated with heparin and discharged on warfarin without neurological sequelae or further seizures. The case was reported to the US Vaccine Surveillance System. CONCLUSIONS mRNA vaccine-related CVST is an extremely rare phenomenon. More data are needed to establish causality and understand the role of vaccine-related immune response resulting in thrombotic events with or without TTS.


Subject(s)
COVID-19 Vaccines/adverse effects , COVID-19 , Sinus Thrombosis, Intracranial , Subarachnoid Hemorrhage , COVID-19/prevention & control , Humans , Male , Middle Aged , RNA, Messenger , Sinus Thrombosis, Intracranial/etiology , Subarachnoid Hemorrhage/etiology , United States , Vaccination/adverse effects
5.
Rinsho Shinkeigaku ; 61(9): 594-601, 2021 Sep 28.
Article in Japanese | MEDLINE | ID: covidwho-1344506

ABSTRACT

Vaccines are important in managing the COVID-19 pandemic caused by SARS-CoV-2. Despite the very low incidence, severe cases of thrombosis with thrombocytopenia after COVID-19 vaccination termed as Thrombosis with Thrombocytopenia Syndrome (TTS) have been reported. TTS clinically resembles autoimmune heparin-induced thrombocytopenia. TTS can cause disability and even death. It usually presents 4-28 days after vaccination characterized by thrombocytopenia and progressive thrombosis, often causing cerebral vein/venous thrombosis (CVT) and splanchnic venous thrombosis. We should avoid all forms of heparin and platelet transfusion. While awaiting further information on the pathophysiological mechanism and treatment of TTS, clinicians should be aware of TTS with CVT in patients receiving COVID-19 vaccinations. This new syndrome of TTS is an active area of investigation globally. Here, we review the available literature.


Subject(s)
COVID-19 Vaccines/adverse effects , COVID-19/prevention & control , Cerebral Veins , Sinus Thrombosis, Intracranial/etiology , Thrombocytopenia/etiology , Adult , COVID-19/virology , Female , Humans , Immunoglobulins, Intravenous/administration & dosage , Male , Middle Aged , SARS-CoV-2 , Sinus Thrombosis, Intracranial/diagnosis , Sinus Thrombosis, Intracranial/epidemiology , Sinus Thrombosis, Intracranial/therapy , Syndrome , Thrombocytopenia/diagnosis , Thrombocytopenia/epidemiology , Thrombocytopenia/therapy , Time Factors
6.
JAMA ; 325(24): 2448-2456, 2021 06 22.
Article in English | MEDLINE | ID: covidwho-1318650

ABSTRACT

Importance: Cerebral venous sinus thrombosis (CVST) with thrombocytopenia, a rare and serious condition, has been described in Europe following receipt of the ChAdOx1 nCoV-19 vaccine (Oxford/AstraZeneca), which uses a chimpanzee adenoviral vector. A mechanism similar to autoimmune heparin-induced thrombocytopenia (HIT) has been proposed. In the US, the Ad26.COV2.S COVID-19 vaccine (Janssen/Johnson & Johnson), which uses a human adenoviral vector, received Emergency Use Authorization (EUA) on February 27, 2021. By April 12, 2021, approximately 7 million Ad26.COV2.S vaccine doses had been given in the US, and 6 cases of CVST with thrombocytopenia had been identified among the recipients, resulting in a temporary national pause in vaccination with this product on April 13, 2021. Objective: To describe reports of CVST with thrombocytopenia following Ad26.COV2.S vaccine receipt. Design, Setting, and Participants: Case series of 12 US patients with CVST and thrombocytopenia following use of Ad26.COV2.S vaccine under EUA reported to the Vaccine Adverse Event Reporting System (VAERS) from March 2 to April 21, 2021 (with follow-up reported through April 21, 2021). Exposures: Receipt of Ad26.COV2.S vaccine. Main Outcomes and Measures: Clinical course, imaging, laboratory tests, and outcomes after CVST diagnosis obtained from VAERS reports, medical record review, and discussion with clinicians. Results: Patients' ages ranged from 18 to younger than 60 years; all were White women, reported from 11 states. Seven patients had at least 1 CVST risk factor, including obesity (n = 6), hypothyroidism (n = 1), and oral contraceptive use (n = 1); none had documented prior heparin exposure. Time from Ad26.COV2.S vaccination to symptom onset ranged from 6 to 15 days. Eleven patients initially presented with headache; 1 patient initially presented with back pain and later developed headache. Of the 12 patients with CVST, 7 also had intracerebral hemorrhage; 8 had non-CVST thromboses. After diagnosis of CVST, 6 patients initially received heparin treatment. Platelet nadir ranged from 9 ×103/µL to 127 ×103/µL. All 11 patients tested for the heparin-platelet factor 4 HIT antibody by enzyme-linked immunosorbent assay (ELISA) screening had positive results. All patients were hospitalized (10 in an intensive care unit [ICU]). As of April 21, 2021, outcomes were death (n = 3), continued ICU care (n = 3), continued non-ICU hospitalization (n = 2), and discharged home (n = 4). Conclusions and Relevance: The initial 12 US cases of CVST with thrombocytopenia after Ad26.COV2.S vaccination represent serious events. This case series may inform clinical guidance as Ad26.COV2.S vaccination resumes in the US as well as investigations into the potential relationship between Ad26.COV2.S vaccine and CVST with thrombocytopenia.


Subject(s)
COVID-19 Vaccines/adverse effects , Sinus Thrombosis, Intracranial/etiology , Thrombocytopenia/etiology , Adolescent , Adult , Critical Care , Fatal Outcome , Female , Headache/etiology , Humans , Middle Aged , Platelet Count , Sinus Thrombosis, Intracranial/therapy , Thrombocytopenia/therapy
8.
Ann Emerg Med ; 78(4): 511-514, 2021 10.
Article in English | MEDLINE | ID: covidwho-1293546

ABSTRACT

Vaccine-induced thrombotic thrombocytopenia is a newly described disease process in the setting of expanding access to COVID-19 vaccination. The United States Centers for Disease Control and Prevention recommends treatment with an alternative to heparin in patients suspected of having vaccine-induced thrombotic thrombocytopenia. At this time there have been no reported outcomes from the treatment of vaccine-induced thrombotic thrombocytopenia with bivalirudin as a heparin alternative. We describe the early outcomes from the treatment of vaccine-induced thrombotic thrombocytopenia with bivalirudin as a heparin alternative. A 40-year-old Caucasian woman was found to have thrombocytopenia, cerebral venous sinus thrombosis, and pulmonary embolism following vaccination for COVID-19 with Ad26.COV2.S. She exhibited a steady rise in platelet count: 20×109/L at hospital day 0, 115×109/L at discharge on hospital day 6, and 182×109/L on outpatient follow-up on day 9. While the patient exhibited a transient drop in hemoglobin, there was no clinical evidence of bleeding. This patient did not demonstrate any clinical sequelae of thrombosis, and she reported resolution of her headache. Vaccination with Ad26.COV2.S appears to be associated with a small but significant risk for thrombotic thrombocytopenia within 13 days of receipt. The Centers for Disease Control and Prevention guidance to consider an alternative to heparin was not accompanied by specifically recommended alternatives. A single patient treated with bivalirudin for suspected vaccine-induced thrombotic thrombocytopenia subsequently experienced symptom improvement and a rise in platelet count and did not demonstrate any immediate negative outcomes. A provider may consider bivalirudin as an alternative to heparin in patients with suspected vaccine-induced thrombotic thrombocytopenia following Ad26.COV2.S vaccination, pending more definitive research.


Subject(s)
COVID-19 Vaccines/adverse effects , Fibrinolytic Agents/therapeutic use , Peptide Fragments/therapeutic use , Sinus Thrombosis, Intracranial/drug therapy , Thrombocytopenia/drug therapy , Adult , Blood Chemical Analysis , Blood Physiological Phenomena , COVID-19/prevention & control , Female , Hirudins , Humans , Pulmonary Embolism/drug therapy , Pulmonary Embolism/etiology , Recombinant Proteins/therapeutic use , Sinus Thrombosis, Intracranial/etiology , Thrombocytopenia/etiology
9.
Clin Appl Thromb Hemost ; 27: 10760296211021498, 2021.
Article in English | MEDLINE | ID: covidwho-1249538

ABSTRACT

Today the coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has become a global health problem. After more than a year with the pandemic, although our knowledge has progressed on COVID-19, there are still many unknowns in virological, pathophysiological and immunological aspects. It is obvious that the most efficient solution to end this pandemic are safe and efficient vaccines. This manuscript summarizes the pathophysiological and thrombotic features of COVID-19 and the safety and efficacy of currently approved COVID-19 vaccines with an aim to clarify the recent concerns of thromboembolic events after COVID-19 vaccination. The influx of newer information is rapid, requiring periodic updates and objective assessment of the data on the pathogenesis of COVID-19 variants and the safety and efficacy of currently available vaccines.


Subject(s)
COVID-19 Vaccines/adverse effects , COVID-19/prevention & control , SARS-CoV-2 , Thrombosis/etiology , Autoantibodies/biosynthesis , COVID-19/epidemiology , COVID-19/physiopathology , COVID-19 Vaccines/genetics , COVID-19 Vaccines/immunology , Clinical Trials as Topic , Disseminated Intravascular Coagulation/epidemiology , Disseminated Intravascular Coagulation/etiology , Drug Approval , Female , Genetic Vectors , Glycosaminoglycans/immunology , Humans , Male , Models, Cardiovascular , Pandemics/prevention & control , Platelet Factor 4/immunology , SARS-CoV-2/genetics , SARS-CoV-2/immunology , SARS-CoV-2/pathogenicity , Safety , Sinus Thrombosis, Intracranial/epidemiology , Sinus Thrombosis, Intracranial/etiology , Thrombosis/epidemiology , Thrombosis/physiopathology , Vaccines, Inactivated/adverse effects , Vaccines, Inactivated/genetics , Vaccines, Inactivated/immunology , Vaccines, Synthetic/adverse effects , Vaccines, Synthetic/genetics , Vaccines, Synthetic/immunology
14.
J Stroke Cerebrovasc Dis ; 30(6): 105733, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1117174

ABSTRACT

BACKGROUND: COVID-19 infection has been known to predispose patients to both arterial and venous thromboembolic events such as deep venous thrombosis, pulmonary embolism, myocardial infarction, and stroke. A few reports from the literature suggest that Cerebral Venous Sinus Thrombosis (CVSTs) may be a direct complication of COVID-19. OBJECTIVE: To review the clinical and radiological presentation of COVID-19 positive patients diagnosed with CVST. METHODS: This was a multicenter, cross-sectional, retrospective study of patients diagnosed with CVST and COVID-19 reviewed from March 1, 2020 to November 8, 2020. We evaluated their clinical presentations, risk factors, clinical management, and outcome. We reviewed all published cases of CVST in patients with COVID-19 infection from January 1, 2020 to November 13, 2020. RESULTS: There were 8 patients diagnosed with CVST and COVID-19 during the study period at 7 out of 31 participating centers. Patients in our case series were mostly female (7/8, 87.5%). Most patients presented with non-specific symptoms such as headache (50%), fever (50%), and gastrointestinal symptoms (75%). Several patients presented with focal neurologic deficits (2/8, 25%) or decreased consciousness (2/8, 25%). D-dimer and inflammatory biomarkers were significantly elevated relative to reference ranges in patients with available laboratory data. The superior sagittal and transverse sinuses were the most common sites for acute CVST formation (6/8, 75%). Median time to onset of focal neurologic deficit from initial COVID-19 diagnosis was 3 days (interquartile range 0.75-3 days). Median time from onset of COVID-19 symptoms to CVST radiologic diagnosis was 11 days (interquartile range 6-16.75 days). Mortality was low in this cohort (1/8 or 12.5%). CONCLUSIONS: Clinicians should consider the risk of acute CVST in patients positive for COVID-19, especially if neurological symptoms develop.


Subject(s)
COVID-19/complications , COVID-19/epidemiology , Sinus Thrombosis, Intracranial/epidemiology , Sinus Thrombosis, Intracranial/etiology , Adult , Aged , Aged, 80 and over , Biomarkers/analysis , COVID-19/mortality , Cranial Sinuses/pathology , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Nervous System Diseases/etiology , Registries , Retrospective Studies , Risk Factors , Sinus Thrombosis, Intracranial/mortality , Tomography, X-Ray Computed , Treatment Outcome
15.
J Neurol Sci ; 419: 117183, 2020 12 15.
Article in English | MEDLINE | ID: covidwho-1023662

ABSTRACT

BACKGROUND: SARS-CoV-2 induced coagulopathy can lead to thrombotic complications such as stroke. Cerebral venous sinus thrombosis (CVST) is a less common type of stroke which might be triggered by COVID-19. We present a series of CVST cases with SARS-CoV-2 infection. METHODS: In a multinational retrospective study, we collected all cases of CVST in SARS-CoV-2 infected patients admitted to nine tertiary stroke centers from the beginning of the pandemic to June 30th, 2020. We compared the demographics, clinical and radiological characteristics, risk factors, and outcome of these patients with a control group of non-SARS-CoV-2 infected CVST patients in the same seasonal period of the years 2012-2016 from the country where the majority of cases were recruited. RESULTS: A total of 13 patients fulfilled the inclusion criteria (62% women, mean age 50.9 ± 11.2 years). Six patients were discharged with good outcomes (mRS ≤ 2) and three patients died in hospital. Compared to the control group, the SARS-CoV-2 infected patients were significantly older (50.9 versus 36.7 years, p < 0.001), had a lower rate of identified CVST risk factors (23.1% versus 84.2%, p < 0.001), had more frequent cortical vein involvement (38.5% versus 10.5%, p: 0.025), and a non-significant higher rate of in-hospital mortality (23.1% versus 5.3%, p: 0.073). CONCLUSION: CVST should be considered as potential comorbidity in SARS-CoV-2 infected patients presenting with neurological symptoms. Our data suggest that compared to non-SARS-CoV-2 infected patients, CVST occurs in older patients, with lower rates of known CVST risk factors and might lead to a poorer outcome in the SARS-CoV-2 infected group.


Subject(s)
COVID-19/complications , SARS-CoV-2 , Sinus Thrombosis, Intracranial/etiology , Adult , Aged , COVID-19/blood , Female , Humans , Length of Stay/statistics & numerical data , Male , Middle Aged , Pandemics , Retrospective Studies , Sinus Thrombosis, Intracranial/diagnostic imaging , Tertiary Care Centers/statistics & numerical data , Thrombophilia/etiology
17.
Ann Neurol ; 89(4): 657-665, 2021 04.
Article in English | MEDLINE | ID: covidwho-979540

ABSTRACT

OBJECTIVE: Severe complications of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) include arterial ischemic stroke (AIS) in adults and multisystem inflammatory syndrome in children. Whether stroke is a frequent complication of pediatric SARS-CoV-2 is unknown. This study aimed to determine the proportion of pediatric SARS-CoV-2 cases with ischemic stroke and the proportion of incident pediatric strokes with SARS-CoV-2 in the first 3 months of the pandemic in an international cohort. METHODS: We surveyed 61 international sites with pediatric stroke expertise. Survey questions included: numbers of hospitalized pediatric (≤ 18 years) patients with SARS-CoV-2; numbers of incident neonatal and childhood ischemic strokes; frequency of SARS-CoV-2 testing for pediatric patients with stroke; and numbers of stroke cases positive for SARS-CoV-2 from March 1 to May 31, 2020. RESULTS: Of 42 centers with SARS-CoV-2 hospitalization numbers, 8 of 971 (0.82%) pediatric patients with SARS-CoV-2 had ischemic strokes. Proportions of stroke cases positive for SARS-CoV-2 from March to May 2020 were: 1 of 108 with neonatal AIS (0.9%), 0 of 33 with neonatal cerebral sinovenous thrombosis (CSVT; 0%), 6 of 166 with childhood AIS (3.6%), and 1 of 54 with childhood CSVT (1.9%). However, only 30.5% of neonates and 60% of children with strokes were tested for SARS-CoV-2. Therefore, these proportions represent 2.9, 0, 6.1, and 3.0% of stroke cases tested for SARS-CoV-2. Seven of 8 patients with SARS-CoV-2 had additional established stroke risk factors. INTERPRETATION: As in adults, pediatric stroke is an infrequent complication of SARS-CoV-2, and SARS-CoV-2 was detected in only 4.6% of pediatric patients with ischemic stroke tested for the virus. However, < 50% of strokes were tested. To understand the role of SARS-CoV-2 in pediatric stroke better, SARS-CoV-2 testing should be considered in pediatric patients with stroke as the pandemic continues. ANN NEUROL 2021;89:657-665.


Subject(s)
COVID-19/epidemiology , Ischemic Stroke/epidemiology , Sinus Thrombosis, Intracranial/epidemiology , Systemic Inflammatory Response Syndrome/epidemiology , Adolescent , COVID-19/complications , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Ischemic Stroke/etiology , Male , SARS-CoV-2 , Sinus Thrombosis, Intracranial/etiology , Surveys and Questionnaires , Systemic Inflammatory Response Syndrome/complications
18.
J Stroke Cerebrovasc Dis ; 30(1): 105434, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-941358

ABSTRACT

SARS-CoV-2, the virus responsible for novel Coronavirus (COVID-19) infection, has recently been associated with a myriad of hematologic derangements; in particular, an unusually high incidence of venous thromboembolism has been reported in patients with COVID-19 infection. It is postulated that either the cytokine storm induced by the viral infection or endothelial damage caused by viral binding to the ACE-2 receptor may activate a cascade leading to a hypercoaguable state. Although pulmonary embolism and deep venous thrombosis have been well described in patients with COVID-19 infection, there is a paucity of literature on cerebral venous sinus thrombosis (cVST) associated with COVID-19 infection. cVST is an uncommon etiology of stroke and has a higher occurrence in women and young people. We report a series of three patients at our institution with confirmed COVID-19 infection and venous sinus thrombosis, two of whom were male and one female. These cases fall outside the typical demographic of patients with cVST, potentially attributable to COVID-19 induced hypercoaguability. This illustrates the importance of maintaining a high index of suspicion for cVST in patients with COVID-19 infection, particularly those with unexplained cerebral hemorrhage, or infarcts with an atypical pattern for arterial occlusive disease.


Subject(s)
COVID-19/complications , Sinus Thrombosis, Intracranial/etiology , Stroke/etiology , Thromboembolism/etiology , Venous Thrombosis/etiology , Adolescent , Adult , Aged , COVID-19/diagnosis , COVID-19/therapy , Fatal Outcome , Female , Humans , Male , Sinus Thrombosis, Intracranial/diagnostic imaging , Sinus Thrombosis, Intracranial/therapy , Stroke/diagnostic imaging , Stroke/therapy , Thromboembolism/diagnostic imaging , Thromboembolism/therapy , Treatment Outcome , Venous Thrombosis/diagnostic imaging , Venous Thrombosis/therapy
19.
Ann Clin Transl Neurol ; 8(1): 300-301, 2021 01.
Article in English | MEDLINE | ID: covidwho-925534

ABSTRACT

A 69-year-old man with uncontrolled type 2 diabetes presented to an outside hospital with altered mental status. He progressed from being argumentative to encephalopathic and agitated by the evening with urinary frequency, urinary urgency, nausea, and vomiting. His vital signs were normal, and he had no focal neurological deficits on presentation. He was generally encephalopathic, only groaning with no ability to follow commands. He was found to have diabetic ketoacidosis on initial labs. A left parietal hypodensity on CT Head was found, and he was positive for Sars-COV-2.


Subject(s)
Brain Diseases/physiopathology , COVID-19/physiopathology , Cerebral Veins , Diabetic Ketoacidosis/physiopathology , Sinus Thrombosis, Intracranial/physiopathology , Aged , Brain Diseases/etiology , COVID-19/complications , COVID-19/diagnostic imaging , Diabetes Mellitus, Type 2/complications , Diabetic Ketoacidosis/etiology , Humans , Magnetic Resonance Imaging , Male , SARS-CoV-2 , Sinus Thrombosis, Intracranial/diagnostic imaging , Sinus Thrombosis, Intracranial/etiology , Thrombosis/diagnostic imaging , Thrombosis/etiology , Thrombosis/physiopathology , Tomography, X-Ray Computed
20.
J Stroke Cerebrovasc Dis ; 29(12): 105412, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-907409

ABSTRACT

INTRODUCTION: Early studies suggest that acute cerebrovascular events may be common in patients with coronavirus disease 2019 (COVID-19) and may be associated with a high mortality rate. Most cerebrovascular events described have been ischemic strokes, but both intracerebral hemorrhage and rarely cerebral venous sinus thrombosis (CVST) have also been reported. The diagnosis of CVST can be elusive, with wide-ranging and nonspecific presenting symptoms that can include headache or altered sensorium alone. OBJECTIVE: To describe the presentation, barriers to diagnosis, treatment, and outcome of CVST in patients with COVID-19. METHODS: We abstracted data on all patients diagnosed with CVST and COVID-19 from March 1 to August 9, 2020 at Boston Medical Center. Subsequently, we reviewed the literature and extracted all published cases of CVST in patients with COVID-19 from January 1, 2020 through August 9, 2020 and included all studies with case descriptions. RESULTS: We describe the clinical features and management of CVST in 3 women with COVID-19 who developed CVST days to months after initial COVID-19 symptoms. Two patients presented with encephalopathy and without focal neurologic deficits, while one presented with visual symptoms. All patients were treated with intravenous hydration and anticoagulation. None suffered hemorrhagic complications, and all were discharged home. We identified 12 other patients with CVST in the setting of COVID-19 via literature search. There was a female predominance (54.5%), most patients presented with altered sensorium (54.5%), and there was a high mortality rate (36.4%). CONCLUSIONS: During this pandemic, clinicians should maintain a high index of suspicion for CVST in patients with a recent history of COVID-19 presenting with non-specific neurological symptoms such as headache to provide expedient management and prevent complications. The limited data suggests that CVST in COVID-19 is more prevalent in females and may be associated with high mortality.


Subject(s)
COVID-19/complications , Sinus Thrombosis, Intracranial/etiology , Venous Thrombosis/etiology , Adult , Aged , Anticoagulants/therapeutic use , COVID-19/diagnosis , COVID-19/therapy , Female , Fluid Therapy , Humans , Male , Middle Aged , Risk Factors , Sinus Thrombosis, Intracranial/diagnostic imaging , Sinus Thrombosis, Intracranial/therapy , Treatment Outcome , Venous Thrombosis/diagnostic imaging , Venous Thrombosis/therapy
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