Endovascular treatment for vaccine-induced cerebral venous sinus thrombosis and thrombocytopenia following ChAdOx1 nCoV-19 vaccination: a report of three cases.

BACKGROUND: Vaccine-induced thrombosis and thrombocytopenia (VITT) is a rare complication following ChAdOx1 nCoV-19 vaccination. Cerebral venous sinus thrombosis (CVST) is overrepresented in VITT and is often associated with multifocal venous thromboses, concomitant hemorrhage and poor outcomes. Hitherto, endovascular treatments have not been reviewed in VITT-related CVST. METHODS: Patient records from a tertiary neurosciences center were reviewed to identify patients who had endovascular treatment for CVST in VITT. RESULTS: Patient records from 1 January 2021 to 20 July 2021 identified three patients who underwent endovascular treatment for CVST in the context of VITT. All were female and the median age was 52 years. The location of the CVST was highly variable. Two-thirds of the patients had multifocal dural sinus thromboses (sigmoid, transverse, straight and superior sagittal) as well as internal jugular vein thromboses. Intracerebral hemorrhage occurred in all patients; subarachnoid blood was noted in two of them, and intraparenchymal hemorrhage occurred in all. There was one periprocedural parenchymal extravasation which abated on temporary cessation of anticoagulation. Outcome data revealed a 90-day modified Rankin Scale (mRS) score of 2 in all cases. CONCLUSIONS: We demonstrate that endovascular treatment for VITT-associated CVST is feasible and can be safe in cases that deteriorate despite medical therapy. Extensive clot burden, concomitant hemorrhage, rapid clinical progression and persistent rises in intracranial pressure should initiate multidisciplinary team discussion for endovascular treatment in appropriate cases.

The Hospitalization Rate of Cerebral Venous Sinus Thrombosis before and during COVID-19 Pandemic Era: A Single-Center Retrospective Cohort Study.

OBJECTIVES: There are several reports of the association between SARS-CoV-2 infection (COVID-19) and cerebral venous sinus thrombosis (CVST). In this study, we aimed to compare the hospitalization rate of CVST before and during the COVID-19 pandemic (before vaccination program). MATERIALS AND METHODS: In this retrospective cohort study, the hospitalization rate of adult CVST patients in Namazi hospital, a tertiary referral center in the south of Iran, was compared in two periods of time. We defined March 2018 to March 2019 as the pre-COVID-19 period and March 2020 to March 2021 as the COVID-19 period. RESULTS: 50 and 77 adult CVST patients were hospitalized in the pre-COVID-19 and COVID-19 periods, respectively. The crude CVST hospitalization rate increased from 14.33 in the pre-COVID-19 period to 21.7 per million in the COVID-19 era (P = 0.021). However, after age and sex adjustment, the incremental trend in hospitalization rate was not significant (95% CrI: -2.2, 5.14). Patients > 50-year-old were more often hospitalized in the COVID-19 period (P = 0.042). SARS-CoV-2 PCR test was done in 49.3% out of all COVID-19 period patients, which were positive in 6.5%. Modified Rankin Scale (mRS) score ≥3 at three-month follow-up was associated with age (P = 0.015) and malignancy (P = 0.014) in pre-COVID period; and was associated with age (P = 0.025), altered mental status on admission time (P<0.001), malignancy (P = 0.041) and COVID-19 infection (P = 0.008) in COVID-19 period. CONCLUSION: Since there was a more dismal outcome in COVID-19 associated CVST, a high index of suspicion for CVST among COVID-19 positive is recommended.

Management and Outcomes of COVID - 19 Associated Cerebral Venous Sinus Thrombosis.

BACKGROUND: Systemic hyper-coagulabilty leading to micro and macro thrombosis is a known complication of Coronavirus disease - 2019(COVID -19). The postulated mechanism appears to be the viral activation of endothelium, triggering the coagulation pathways. Thrombosis of the cerebral veins and sinuses (CVT), a potentially serious condition, has been increasingly reported with COVID - 19 infection. In this clinical study we attempt to describe the clinical profile, investigations and outcomes of patients with COVID- 19 associated CVT. METHODS: This is a single center prospective observational study from South India. The study included patients (aged >18 years) with concomitant COVID infection and CVT. The clinical, laboratory, imaging characteristics, management and outcomes were described and compared with COVID negative CVT patients. RESULTS: Out of 97 cases of CVT treated at our center during the first and second waves of the COVID pandemic 11/97 (11%) were COVID related CVT. Among these 11 patients, 9 (81%) had presented with only CVT related symptoms and signs and were tested positive for COVID - 19 infection during the pre-hospitalization screening. Respiratory symptoms were absent in 90% of the patients. Headache (100%) and seizures (90%) were the common presenting symptoms. The median time to diagnosis was 6 hours, from presentation to the emergency department. Transverse sinus was involved 10/11 (90%) and majority of them (9/11) had Haemorrhagic Venous Infarction (HVI). Acute inflammatory markers were elevated in comparison with non COVID CVT patients, with the mean serum D-dimer being 2462.75 ng/ml and the C-reactive protein was 64.5 mg/dl. Three patients (30%) underwent decompressive hemicraniectomy (DHC) because of large hemispheric HVI. All patients survived in the COVID CVT group while the mortality in the non COVID group was 4%. At 6 months follow up excellent outcome (modified Rankin Scale (mRS) score of 0-2) was noted equally in both groups. CONCLUSIONS: Symptoms and signs of CVT may be the only presentation of COVID-19 infection. Prompt recognition and aggressive medical management including DHC offers excellent outcomes.

[Cerebral vein/venous sinus thrombosis with thrombocytopenia syndrome after COVID-19 vaccination].

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.

US Case Reports of Cerebral Venous Sinus Thrombosis With Thrombocytopenia After Ad26.COV2.S Vaccination, March 2 to April 21, 2021.

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.

Cerebral Venous Sinus Thrombosis in COVID-19 Infection: A Case Series and Review of The Literature.

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.

Cerebral Venous Sinus Thromboses in Patients with SARS-CoV-2 Infection: Three Cases and a Review of the Literature.

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.