Successful Treatment of Cerebral Venous Thrombosis with Rivaroxaban: A Case Report with Brief Review

A small randomized controlled trial suggested that dabigatran may be as effective as warfarin in the treatment of cerebral venous thrombosis (CVT). We aimed to compare direct oral anticoagulants (DOACs) to warfarin in a real-world CVT cohort. This multicenter international retrospective study (United States, Europe, New Zealand) included consecutive patients with CVT treated with oral anticoagulation from January 2015 to December 2020. We abstracted demographics and CVT risk factors, hypercoagulable labs, baseline imaging data, and clinical and radiological outcomes from medical records. We used adjusted inverse probability of treatment weighted Cox-regression models to compare recurrent cerebral or systemic venous thrombosis, death, and major hemorrhage in patients treated with warfarin versus DOACs. We performed adjusted inverse probability of treatment weighted logistic regression to compare recanalization rates on follow-up imaging across the 2 treatments groups. Among 1025 CVT patients across 27 centers, 845 patients met our inclusion criteria. Mean age was 44.8 years, 64.7% were women; 33.0% received DOAC only, 51.8% received warfarin only, and 15.1% received both treatments at different times. During a median follow-up of 345 (interquartile range, 140-720) days, there were 5.68 recurrent venous thrombosis, 3.77 major hemorrhages, and 1.84 deaths per 100 patient-years. Among 525 patients who met recanalization analysis inclusion criteria, 36.6% had complete, 48.2% had partial, and 15.2% had no recanalization. When compared with warfarin, DOAC treatment was associated with similar risk of recurrent venous thrombosis (aHR, 0.94 [95% CI, 0.51-1.73]; P=0.84), death (aHR, 0.78 [95% CI, 0.22-2.76]; P=0.70), and rate of partial/complete recanalization (aOR, 0.92 [95% CI, 0.48-1.73]; P=0.79), but a lower risk of major hemorrhage (aHR, 0.35 [95% CI, 0.15-0.82]; P=0.02). In patients with CVT, treatment with DOACs was associated with similar clinical and radiographic outcomes and favorable safety profile when compared with warfarin treatment. Our findings need confirmation by large prospective or randomized studies.

Direct oral anticoagulants versus vitamin K antagonists for cerebral venous thrombosis (DOAC-CVT): an international, prospective, observational cohort study.

Background and purposeCerebral venous thrombosis causes disability from venous infarct and hemorrhage and potential mortality. Anticoagulation improves survival and disability outcomes, yet direct oral anticoagulants are currently not indicated in cerebral venous thrombosis due to lack of evidence, despite being on the market for nearly a decade. This systematic review will collate evidence of reported safety and efficacy of direct oral anticoagulant therapy in cerebral venous thrombosis.MethodsA search strategy was developed with a research librarian and registered on a protocol database (PROSPERO CRD42017078398). All published studies from MEDLINE and EMBASE up to February 2019 containing patients diagnosed with cerebral venous thrombosis who were treated with a direct oral anticoagulant (dabigatran, rivaroxaban, apixaban, or edoxaban) will be included. A risk of bias analysis will be performed to evaluate quality of studies overall.DiscussionCurrent guidelines in the treatment of cerebral vein thrombosis dating back to 2011 from the American Heart Association/American Stroke Association endorse the utility of anticoagulation for the treatment of cerebral vein thrombosis; however, they did not support the use of direct oral anticoagulants. Updated guidelines from the European Stroke Organization, endorsed by the European Academy of Neurology in 2017, also refute utilization of direct oral anticoagulants due to a lack of evidence. There have been nearly 10 years of experience with direct oral anticoagulants in the treatment of venous thrombosis and prevention of stroke in patients with atrial fibrillation, with purported efficacy and safety in comparison with heparins and vitamin K antagonists. Our goal is to undertake a systematic review to assess the effectiveness and safety of direct oral anticoagulants in patients with cerebral vein thrombosis to help guide clinical decision-making for patients unable to take heparins or vitamin K antagonists and to direct future studies to contribute further to an area of certain evidence-based needs.Systematic review registrationPROSPERO CRD42017078398

Diagnosis and Management of Cerebral Venous Sinus Thrombosis With Vaccine-Induced Immune Thrombotic Thrombocytopenia.

BACKGROUND: Cerebral venous thrombosis is a multifactorial and difficult-to-diagnose disease, complicated by venous stroke, intracerebral hemorrhage, progressive cerebral edema, dislocation syndrome, and even death. The broad variability of clinical symptoms and lack of pathognomonic manifestations complicate timely diagnosis of cerebral venous thrombosis. AIM: To identify significant risk factors for cerebral venous thrombosis and to evaluate the dynamics of neuroimaging findings at 1, 3, and 6 months after cerebral venous thrombosis onset in young and middle-aged patients with a history of COVID-19, comparing outcomes between those treated with direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs). METHODS: Young and middle-aged patients with a history of novel coronavirus infection (COVID-19) were examined and divided into two groups depending on the presence or absence of cerebral venous thrombosis. The main risk factors, structural features of the major arteries and cerebral venous sinuses, as well as the course of cerebral venous and sinus thrombosis during anticoagulant therapy (with direct oral anticoagulants and vitamin K antagonists) at 1, 3, and 6 months after the development of cerebral venous thrombosis were analyzed. RESULTS: We examined 120 young and middle-aged patients with COVID-19 divided into 2 groups: Group I – 70 patients who developed cerebral venous thrombosis during COVID-19 – 21 (30%) men and 49 (70%) women; Group II – 50 patients who had COVID-19 without cerebral venous thrombosis development – 27 (54%) men and 23 (46%) women. The main risk factor for developing cerebral venous thrombosis among women in the first group (with cerebral venous thrombosis during COVID-19) compared to the second group (patients who had COVID-19 without developing cerebral venous thrombosis) was the use of combined oral contraceptives: 22.9% and 4.0%, respectively (р = 0.001). Among group I patients, 32 (45.7%) cases of cerebral venous thrombosis were accompanied by the development of venous stroke: ischemic in 13 (18.6%) patients, hemorrhagic in 7 (10%), mixed (ischemic stroke with hemorrhagic infiltration) in 12 (17.1%) patients. In a comparative analysis of the variants of the structure of the cerebral arteries (absence of the posterior communicating arteries, pathological tortuosity of the internal carotid artery [ICA], trifurcation of the ICA, open arterial circle of Willis) and venous sinuses (presence of hypo-/aplasia), no statistically significant difference was detected. The analysis of the course of cerebral venous thrombosis during treatment with vitamin K antagonists (warfarin) and direct oral anticoagulants in 53 patients with cerebral venous thrombosis (age 41 ± 12 years) at 1,3, and 6 months after the development of cerebral venous thrombosis onset showed that with anticoagulants, recanalization was observed in 44 (83%) patients: complete – in 21 patients (47.7%), partial – in 23 (52.3%). Recanalization was absent in 9 (17.0%) cases. No recurrent cerebral venous thrombosis cases were observed among the study patients. CONCLUSION: Verification of cerebral venous thrombosis in the context of COVID-19 necessitates a detailed examination of risk factors, patient history, assessment of clinical manifestations, and comprehensive implementation of laboratory and instrumental, as well as neuroimaging diagnostic methods. Timely verification and immediate initiation of anticoagulant therapy ensure a relatively favorable prognosis for the disease course.

ObjectivesCurrent guidelines do not recommend direct oral anticoagulants (DOACs) to treat cerebral venous thrombosis (CVT) despite their benefits over standard therapy. We performed a systematic review to summarise the published...

IntroductionCurrent guidelines recommend that patients with cerebral venous thrombosis (CVT) should be treated with vitamin K antagonists (VKAs) for 3–12 months. Direct oral anticoagulants (DOACs), however, are increasingly used in clinical practice. An exploratory randomized controlled trial including 120 patients with CVT suggested that the efficacy and safety profile of dabigatran (a DOAC) is similar to VKAs for the treatment of CVT, but large-scale prospective studies from a real-world setting are lacking.MethodsDOAC-CVT is an international, prospective, observational cohort study comparing DOACs to VKAs for the prevention of recurrent venous thrombotic events after acute CVT. Patients are eligible if they are 18 years or older, have a radiologically confirmed CVT, and have started oral anticoagulant treatment (DOAC or VKA) within 30 days of CVT diagnosis. Patients with an absolute contra-indication for DOACs, such as pregnancy or severe renal insufficiency, are excluded from the study. We aim to recruit at least 500 patients within a three-year recruitment period. The primary endpoint is a composite of recurrent venous thrombosis and major bleeding at 6 months of follow-up. We will calculate an adjusted odds ratio for the primary endpoint using propensity score inverse probability treatment weighting.DiscussionDOAC-CVT will provide real-world data on the comparative efficacy and safety of DOACs versus VKAs for the treatment of CVT.Clinical trial registrationClinicalTrials.gov, NCT04660747.

Cerebral venous thrombosis (CVT) is a rare type of cerebrovascular event in which the thrombosis occurs in a vein of the cerebral venous system. The diagnosis could be challenging due to the great clinical variability, but the outcome is favourable in most cases, especially in the case of early diagnosis. Anticoagulant therapy is the core of CVT management and currently consists of heparin in the acute phase followed by vitamin K antagonists (VKAs) in the long term. The ideal duration of anticoagulant therapy is still unclear, and the same criteria for the treatment of extracerebral venous thromboembolism currently apply. In this paper, we reviewed the literature regarding the use of direct oral anticoagulants (DOACs) in CVT since in recent years a considerable number of studies have been published on the use of these drugs in this specific setting. DOACs have already been shown to be equally effective with VKAs in the treatment of venous thromboembolism. In addition to efficacy, DOACs appear to have the same safety profile, being, on the other hand, more manageable, as they do not require close monitoring with continuous personalised dose adjustments. In addition, a further advantage of DOACs over VKAs is the possibility of anticoagulant prophylaxis using a reduced dosage of the drug. In conclusion, although the use of DOACs appears from preliminary studies to be effective and safe in the treatment of CVT, additional studies are needed to include these drugs in the treatment of CVT.

October 2022 Stroke Highlights.

Cerebral venous thrombosis (CVT) causes significant disability and mortality. Current guidelines for CVT management support the initial use of unfractionated heparin or low molecular weight heparin followed by longer-term oral vitamin K antagonist (VKA). There has been increasing, albeit limited, evidence for the use of direct oral anticoagulants (DOAC) as an alternative to VKA. We performed a systematic review and meta-analysis of studies that compared the safety and efficacy of DOACs to VKA in treating CVT. A comprehensive literature search was carried out in Medline, Embase and Cochrane Stroke Group Trials Register using a suitable keyword/MeSH term search strategy. All studies published in English comparing outcomes of patients with CVT treated with DOAC or VKA were included. In total, 6 studies (5 observational studies and 1 randomized clinical trial) comprising 412 patients (age range 16-83years) were analyzed. DOAC was used in 151 patients, while 261 received VKA. The follow-up period was 3-11months. The efficacy of DOACs was comparable with VKA in terms of partial or full thrombus recanalization (RR 1.02, 95% CI 0.89-1.16) and excellent functional recovery with modified Rankin scale < 2 (RR 1.02, 95% CI 0.93-1.13). Patients treated with DOAC developed lower major bleeding events when compared to VKA, although this did not reach statistical significance (RR 0.44, 95% CI 0.12-1.59). We provide preliminary evidence to support DOAC as effective and safe alternatives to VKA in CVT treatment. We await the results of upcoming randomized trials to further support our results and validate the use of DOAC.

Introduction Neurointerventional procedures for Cerebral Venous Thrombosis (CVT) are considered in patients with clinical deterioration or progression of venous infarction/intracerebral hemorrhage despite anticoagulation or major contraindications to anticoagulation. The EmboTrap III revascularization device commonly used for acute ischemic stroke is a dual‐layer segmented stent retriever designed to entrap a broad range of clot compositions and stay apposed to the vessel wall during retrieval. This case illustrates the safety and broadens the application of EmboTrap III for venous thrombectomy. Case Description An 87‐year‐old female with a medical history of Diabetes Mellitus Type 2, Hyperlipidemia, Hypertension, Dementia, and seizures presented with two episodes of generalized tonic‐clonic seizures 2 to 3 days prior to admission and left upper and lower extremity weakness noted on the day of admission. Computed Tomography (CT) head revealed right posterior parasagittal hemorrhage. CT venography (CTV) showed a large filling defect throughout the Superior Sagittal Sinus (SSS) with extension into the bilateral transverse sinuses (TS), sigmoid sinuses (SS), and right internal jugular vein (IJV) consistent with CVT and a moderate‐sized region of venous infarction within the right superior fronto/posterior cingulate gyrus. The EmboTrap III stent retriever, combined with cyclical aspiration, significantly reduced clot burden and restored venous drainage through the SSS. Balloon angioplasty of the bilateral SS and TS allowed for the creation of a channel in the sigmoid and transverse sinuses to achieve optimal catheter access to the SSS and venous drainage. Conclusion The combination of EmboTrap III stent retriever and cereglide 71 aspiration allowed for the safe, complete recanalization of the SSS. While the EmboTrap III is widely used for arterial thrombectomy, its application in venous thrombectomy has not been extensively reported. To our knowledge, this is the first documented case of SSS venous thrombectomy using the EmboTrap III and cereglide 71 aspiration catheter. image image

Background: Cerebral venous thrombosis (CVT) is an uncommon neurological condition usually treated with heparin followed by oral vitamin K antagonists (VKAs). In patients with venous thromboembolism (VTE), compared to VKAs, direct oral anticoagulants (DOACs) offer several advantages. However, there is little data concerning their use in managing CVT. Aims: This retrospective observational study pursued 2 objectives: (1) to investigate clinical characteristics of CVT patients treated with heparin + DOACs vs. heparin + standard treatment; (2) to compare clinical outcomes. Methods: Consecutive CVT patients recruited from January 2016 to March 2018 in 2 French university hospitals (Lyon, Saint-Etienne), and treated with DOACs or VKAs were identified. Radiological evolution, VTE, hemorrhagic events, and antithrombotic medication were recorded. Functional outcome was assessed by the modified Rankin scale score and venous recanalization was assessed by magnetic resonance imaging. Results: Overall, 41 patients were included: 25 (61%) received VKAs and 16 (39%) DOACs. We identified no clinical or radiological features explaining the physicians’ preference for a specific anticoagulation treatment, and age, initial clinical presentation, radiological severity, and individual risk factors thus unlikely guided the choice of anticoagulant. No DOAC patient exhibited clinical or radiological thrombosis aggravation, and the thrombosis completely vanished in 6 (40%). Two of the VKA-treated patients (28.6%) demonstrated complete venous recanalization, whereas 3 others experienced clinical or radiological aggravation versus baseline. There was no major bleeding leading to hospitalization in both groups. Conclusion: The collected data on DOAC efficacy and safety in CVT management appear encouraging, yet needs to be confirmed by larger prospective randomized clinical trials.

Тромбоз мозкових вен і венозний тромбоз мозкових синусів зустрічається рідко (до 1 % від усіх випадків інфарктів мозку). За даними ISCVT (International Study on Cerebral Vein and Dural Sinus Thrombosis, 2004), захворюваність щорічно становить 3–4 випадки на 1 млн у дорослих. Летальність при даному захворюванні становить від 5 до 30 %. Міжнародне дослідження тромбозу мозкових вен та венозних синусів (ISCVT) визначало частоту оклюзій за локалізацією так: поперечний синус — 86 %, верхній сагітальний синус — 62 %, прямий синус — 18 %, кортикальні вени — 17 %, внутрішні яремні вени — 12 %, вена Галена і внутрішні мозкові вени — 11 %. Основними факторами ризику розвитку тромбозу мозкових вен і венозного тромбозу мозкових синусів у популяції є інфекційні запальні процеси (отити, мастоїдити, синусити, септичні стани) і неінфекційні причини: черепно-мозкова травма, пухлини, хірургічні втручання в ділянці голови та шиї, а також імплантація кардіостимулятора чи постановка центрального венозного катетера. Захворювання, що сприяють даній патології: порушення гемодинаміки (застійна серцева недостатність, зневоднення організму), захворювання крові (поліцитемія, серпоподібноклітинна анемія, тромбоцитопенія) і коагулопатії (синдром дисемінованого внутрішньосудинного згортання крові, дефіцит антитромбіну, протеїну С і S), а також тромбофілітичні стани, пов’язані з вагітністю, родами та прийомом пероральних контрацептивів, антифосфоліпідний синдром, системні васкуліти. При цьому в 15 % випадків причина розвитку синус-тромбозу залишається невстановленою. Венозний тромбоз мозкових синусів характеризується дуже різноманітним клінічним перебігом, складною діагностикою, різноманітною етіологією і прогнозом. Одним з ускладнень тромбозу синусів є інсульт, що спостерігається приблизно в 30 % хворих та часто призводить до смерті хворого. У статті подано опис клінічного випадку церебрального венозного тромбозу, що ускладнився несумісним із життям двопівкульним субарахноїдально-паренхіматозним крововиливом.

Cerebral venous thrombosis (CVT), thrombosis of the dural sinus, cerebral veins, or both, is a rare cerebrovascular disease. Although mortality rates after CVT have declined over time, this condition can result in devastating neurologic outcomes. This article reviews the latest literature regarding CVT epidemiology, details new factors associated with the development of CVT, and describes advances in CVT treatment. It also contains a discussion of future directions in the field, including novel diagnostic imaging modalities, and potential strategies to reduce the risks associated with CVT. The incidence of CVT may be as high as 2 per 100,000 adults per year. It remains a difficult condition to diagnose given its variable clinical manifestations and the necessity of neuroimaging for confirmation. The COVID-19 pandemic has revealed a novel CVT trigger, vaccine-induced immune thrombotic thrombocytopenia (VITT), as well as an association between COVID-19 infection and CVT. Although VITT is a very rare event, timely diagnosis and treatment of CVT due to VITT likely improves patient outcomes. Direct oral anticoagulants are currently being used to treat CVT and emerging data suggest that these agents are as safe and effective as vitamin K antagonists. The role of endovascular therapy to treat CVT, despite a recent clinical trial, remains unproven. The incidence of CVT has increased, outcomes have improved, and the use of direct oral anticoagulants to treat CVT represents an important advance in the clinical care of these patients. Rates of CVT as a complication of COVID-19 vaccines using adenoviral vectors are very low (<5 per million vaccine doses administered), with the benefits of COVID-19 vaccination far outweighing the risks.

Cerebral venous thrombosis (CVT) is a potentially life-threatening condition that requires acute recognition and treatment. Diagnosis of CVT is challenging and requires a high index of clinical suspicion. The finding of the "cord sign" in a non-contrast cranial CT is useful for the rapid recognition of CVT in the emergency setting. We describe a patient with CVT in whom the "cord sign" and elevated factor VIII (FVIII) plasma levels were both present. A 45-year-old Caucasian man was brought to the emergency room with headache and a focal seizure. His neurological examination was non-focal. During his evaluation in the ER, a non-contrast cranial CT showed increased density of cortical veins ("cord sign"), vein of Galen, and superior sagittal, transverse and straight sinuses. A brain MRI demonstrated a flow signal void in the superior sagittal sinus, prominent cortical veins, asymmetric flow signal in the right transverse sinus, and subarachnoid hemorrhage adjacent to the superior sagittal sinus. Laboratory work-up was unremarkable and only revealed elevation of FVIII plasma levels. We report the first case of CVT with the "cord sign" and concomitant elevated FVIII. Early recognition of the "cord sign" is warranted for the emergency diagnosis and treatment of CVT.