Bousser MG, Russell RR (eds): Cerebral venous thrombosis. Major problems in neurology, Saunders, New York, vol 33, 1997.
Caso V, Agnelli G, Paciaroni M(eds): Handbook of cerebral venous thrombosis. Frontiers of Neurology and Neuroscience, Karger, Basel, vol 23, 2008.
橋本洋一郎、伊藤康幸、光藤 尚、山本文夫：脳静脈血栓症の症候学．分子脳血管病 2010； 9: 385-391.
Ferro JM, Bousser MG, Canhão P, Coutinho JM, Crassard I, Dentali F, di Minno M, Maino A, Martinelli I, Masuhr F, de Sousa DA, Stam J; European Stroke Organization.
European Stroke Organization guideline for the diagnosis and treatment of cerebral venous thrombosis - Endorsed by the European Academy of Neurology.
Eur Stroke J. 2017 Sep;2(3):195-221. doi: 10.1177/2396987317719364. Epub 2017 Jul 21.
Abstract/Text
The current proposal for cerebral venous thrombosis guideline followed the Grading of Recommendations, Assessment, Development, and Evaluation system, formulating relevant diagnostic and treatment questions, performing systematic reviews of all available evidence and writing recommendations and deciding on their strength on an explicit and transparent manner, based on the quality of available scientific evidence. The guideline addresses both diagnostic and therapeutic topics. We suggest using magnetic resonance or computed tomography angiography for confirming the diagnosis of cerebral venous thrombosis and not screening patients with cerebral venous thrombosis routinely for thrombophilia or cancer. We recommend parenteral anticoagulation in acute cerebral venous thrombosis and decompressive surgery to prevent death due to brain herniation. We suggest to use preferentially low-molecular weight heparin in the acute phase and not using direct oral anticoagulants. We suggest not using steroids and acetazolamide to reduce death or dependency. We suggest using antiepileptics in patients with an early seizure and supratentorial lesions to prevent further early seizures. We could not make recommendations due to very poor quality of evidence concerning duration of anticoagulation after the acute phase, thrombolysis and/or thrombectomy, therapeutic lumbar puncture, and prevention of remote seizures with antiepileptic drugs. We suggest that in women who suffered a previous cerebral venous thrombosis, contraceptives containing oestrogens should be avoided. We suggest that subsequent pregnancies are safe, but use of prophylactic low-molecular weight heparin should be considered throughout pregnancy and puerperium. Multicentre observational and experimental studies are needed to increase the level of evidence supporting recommendations on the diagnosis and management of cerebral venous thrombosis.
Weimar C, Beyer-Westendorf J, Bohmann FO, Hahn G, Halimeh S, Holzhauer S, Kalka C, Knoflach M, Koennecke HC, Masuhr F, Mono ML, Nowak-Göttl U, Scherret E, Schlamann M, Linnemann B.
New recommendations on cerebral venous and dural sinus thrombosis from the German consensus-based (S2k) guideline.
Neurol Res Pract. 2024 Apr 19;6(1):23. doi: 10.1186/s42466-024-00320-9. Epub 2024 Apr 19.
Abstract/Text
Over the last years, new evidence has accumulated on multiple aspects of diagnosis and management of cerebral venous and dural sinus thrombosis (CVT) including identification of new risk factors, studies on interventional treatment as well as treatment with direct oral anticoagulants. Based on the GRADE questions of the European Stroke Organization guideline on this topic, the new German guideline on CVT is a consensus between expert representatives of Austria, Germany and Switzerland. New recommendations include:• CVT occurring in the first weeks after SARS-CoV-2 vaccination with vector vaccines may be associated with severe thrombocytopenia, indicating the presence of a prothrombotic immunogenic cause (Vaccine-induced immune thrombotic thrombocytopenia; VITT).• D-dimer testing to rule out CVT cannot be recommended and should therefore not be routinely performed.• Thrombophilia screening is not generally recommended in patients with CVT. It should be considered in young patients, in spontaneous CVT, in recurrent thrombosis and/or in case of a positive family history of venous thromboembolism, and if a change in therapy results from a positive finding.• Patients with CVT should preferably be treated with low molecular weight heparine (LMWH) instead of unfractionated heparine in the acute phase.• On an individual basis, endovascular recanalization in a neurointerventional center may be considered for patients who deteriorate under adequate anticoagulation.• Despite the overall low level of evidence, surgical decompression should be performed in patients with CVT, parenchymal lesions (congestive edema and/or hemorrhage) and impending incarceration to prevent death.• Following the acute phase, oral anticoagulation with direct oral anticoagulants instead of vitamin K antagonists should be given for 3 to 12 months to enhance recanalization and prevent recurrent CVT as well as extracerebral venous thrombosis.• Women with previous CVT in connection with the use of combined hormonal contraceptives or pregnancy shall refrain from continuing or restarting contraception with oestrogen-progestagen combinations due to an increased risk of recurrence if anticoagulation is no longer used.• Women with previous CVT and without contraindications should receive LMWH prophylaxis during pregnancy and for at least 6 weeks post partum.Although the level of evidence supporting these recommendations is mostly low, evidence from deep venous thrombosis as well as current clinical experience can justify the new recommendations.This article is an abridged translation of the German guideline, which is available online.
© 2024. The Author(s).
Saposnik G, Barinagarrementeria F, Brown RD Jr, Bushnell CD, Cucchiara B, Cushman M, deVeber G, Ferro JM, Tsai FY; American Heart Association Stroke Council and the Council on Epidemiology and Prevention.
Diagnosis and management of cerebral venous thrombosis: a statement for healthcare professionals from the American Heart Association/American Stroke Association.
Stroke. 2011 Apr;42(4):1158-92. doi: 10.1161/STR.0b013e31820a8364. Epub 2011 Feb 3.
Abstract/Text
BACKGROUND: The purpose of this statement is to provide an overview of cerebral venous sinus thrombosis and to provide recommendations for its diagnosis, management, and treatment. The intended audience is physicians and other healthcare providers who are responsible for the diagnosis and management of patients with cerebral venous sinus thrombosis.
METHODS AND RESULTS: Members of the panel were appointed by the American Heart Association Stroke Council's Scientific Statement Oversight Committee and represent different areas of expertise. The panel reviewed the relevant literature with an emphasis on reports published since 1966 and used the American Heart Association levels-of-evidence grading algorithm to rate the evidence and to make recommendations. After approval of the statement by the panel, it underwent peer review and approval by the American Heart Association Science Advisory and Coordinating Committee.
CONCLUSIONS: Evidence-based recommendations are provided for the diagnosis, management, and prevention of recurrence of cerebral venous thrombosis. Recommendations on the evaluation and management of cerebral venous thrombosis during pregnancy and in the pediatric population are provided. Considerations for the management of clinical complications (seizures, hydrocephalus, intracranial hypertension, and neurological deterioration) are also summarized. An algorithm for diagnosis and management of patients with cerebral venous sinus thrombosis is described.
Saposnik G, Bushnell C, Coutinho JM, Field TS, Furie KL, Galadanci N, Kam W, Kirkham FC, McNair ND, Singhal AB, Thijs V, Yang VXD; American Heart Association Stroke Council; Council on Cardiopulmonary, Critical Care, Perioperative and Resuscitation; Council on Cardiovascular and Stroke Nursing; and Council on Hypertension.
Diagnosis and Management of Cerebral Venous Thrombosis: A Scientific Statement From the American Heart Association.
Stroke. 2024 Mar;55(3):e77-e90. doi: 10.1161/STR.0000000000000456. Epub 2024 Jan 29.
Abstract/Text
Cerebral venous thrombosis accounts for 0.5% to 3% of all strokes. The most vulnerable populations include young individuals, women of reproductive age, and patients with a prothrombotic state. The clinical presentation of cerebral venous thrombosis is diverse (eg, headaches, seizures), requiring a high level of clinical suspicion. Its diagnosis is based primarily on magnetic resonance imaging/magnetic resonance venography or computed tomography/computed tomographic venography. The clinical course of cerebral venous thrombosis may be difficult to predict. Death or dependence occurs in 10% to 15% of patients despite intensive medical treatment. This scientific statement provides an update of the 2011 American Heart Association scientific statement for the diagnosis and management of cerebral venous thrombosis. Our focus is on advances in the diagnosis and management decisions of patients with suspected cerebral venous thrombosis. We discuss evidence for the use of anticoagulation and endovascular therapies and considerations for craniectomy. We also provide an algorithm to optimize the management of patients with cerebral venous thrombosis and those with progressive neurological deterioration or thrombus propagation despite maximal medical therapy.
Koopman K, Uyttenboogaart M, Vroomen PC, van der Meer J, De Keyser J, Luijckx GJ.
Development and validation of a predictive outcome score of cerebral venous thrombosis.
J Neurol Sci. 2009 Jan 15;276(1-2):66-8. doi: 10.1016/j.jns.2008.08.033. Epub 2008 Sep 26.
Abstract/Text
BACKGROUND AND PURPOSE: Cerebral venous thrombosis (CVT) is a rare disease with a variable outcome. The aim of this study was to develop and validate a predictive outcome score for CVT patients.
METHODS: The score was based on the 8 predictive variables of poor outcome (modified Rankin Scale score>2) from the International Study on Cerebral Vein and Dural Sinus Thrombosis: age >37, male, mental status disorder, coma, intracranial hemorrhage, deep CVT, CNS infection, and malignancy. To assign a weighted index (WI), the natural logarithm of the hazard ratio of each variable was calculated, multiplied by 10 and rounded to the nearest integer. The individual score of each patient was the sum of the WI. The validation sample consisted of a retrospective single center cohort of 90 CVT patients.
RESULTS: Sixteen patients (18%) had a poor outcome. The predictive score had an area under the receiver operating characteristic curve of 0.81 (95% CI 0.71-0.90). The cut-off score with the maximum sum of sensitivity and specificity was a score> or =14 with sensitivity of 88% (81%-95%) and specificity of 70% (61%-79%). The predictive value of a score<14 for good outcome was 96% (92%-100%), whereas the predictive value of a score> or =14 for poor outcome was 39% (29%-49%).
CONCLUSIONS: This relatively simple predictive outcome score may be useful in CVT patients. A cut-off score of 14 reliably predicts good outcome, but is less accurate in predicting poor outcome.
Einhäupl KM, Villringer A, Meister W, Mehraein S, Garner C, Pellkofer M, Haberl RL, Pfister HW, Schmiedek P.
Heparin treatment in sinus venous thrombosis.
Lancet. 1991 Sep 7;338(8767):597-600. doi: 10.1016/0140-6736(91)90607-q.
Abstract/Text
Treatment of sinus venous thrombosis (SVT) is controversial. Although heparin has been used for this condition, many investigators have opposed its use because of the frequent occurrence of intracranial haemorrhage (ICH) and SVT. Therefore we have evaluated anticoagulation with adjusted-dose intravenous heparin for treatment of aseptic SVT in a randomised, blinded (patient and observer), placebo-controlled study in 20 patients (10 heparin, 10 placebo). The clinical course of the two groups, as judged by a newly designed SVT-severity scale, started to differ in favour of the heparin group after 3 days of treatment (p less than 0.05, Mann-Whitney U-test) and the difference remained significant (p less than 0.01) after 8 days of treatment. After 3 months, 8 of the heparin-treated patients had a complete clinical recovery and 2 had slight residual neurological deficits. In the placebo group, only 1 patient had a complete recovery, 6 patients had neurological deficits, and 3 patients died (p less than 0.01, modified Fisher's exact test). An additional retrospective study on the relation between heparin treatment and ICH in SVT patients was based on 102 patients, 43 of whom had an ICH. 27 of these patients were treated with dose-adjusted, intravenous heparin after the ICH. Of these 27 patients, 4 died (mortality 15%), and 14 patients completely recovered. Of the 13 patients that did not receive heparin after ICH, 9 died (mortality 69%) and only 3 patients completely recovered. We conclude that anticoagulation with dose-adjusted intravenous heparin is an effective treatment in patients with SVT and that ICH is not a contraindication to heparin treatment in these patients.
de Bruijn SF, Stam J.
Randomized, placebo-controlled trial of anticoagulant treatment with low-molecular-weight heparin for cerebral sinus thrombosis.
Stroke. 1999 Mar;30(3):484-8. doi: 10.1161/01.str.30.3.484.
Abstract/Text
BACKGROUND AND PURPOSE: Treatment of cerebral sinus thrombosis with heparin is controversial. We conducted a double-blind, placebo-controlled multicenter trial to examine whether anticoagulant treatment improves outcome in patients with sinus thrombosis.
METHODS: Patients were randomized between body weight-adjusted subcutaneous nadroparin (180 anti-factor Xa units/kg per 24 hours) and matching placebo for 3 weeks (double-blind part of trial), followed by 3 months of oral anticoagulants for patients allocated nadroparin (open part). Patients with cerebral hemorrhage caused by sinus thrombosis were also included.
RESULTS: Sixty patients were enrolled, and none were lost to follow-up. In 1 patient the diagnosis proved wrong after randomization. After 3 weeks, 6 of 30 patients (20%) in the nadroparin group and 7 of 29 patients (24%) in the placebo group had a poor outcome, defined as death or Barthel Index score of <15 (risk difference, -4%; 95% CI, -25 to 17%; NS). After 12 weeks, 4 of 30 patients (13%) in the nadroparin group and 6 of 29 (21%) in the placebo group had a poor outcome, defined as death or Oxford Handicap Score of >/=3 (risk difference, -7%; 95% CI, -26% to 12%; NS). There were no new symptomatic cerebral hemorrhages. One patient in the nadroparin group had a major gastrointestinal hemorrhage, and 1 patient in the placebo group died from clinically suspected pulmonary embolism.
CONCLUSIONS: Patients with cerebral sinus thrombosis treated with anticoagulants (low-molecular-weight heparin followed by oral anticoagulation) had a favorable outcome more often than controls, but the difference was not statistically significant. Anticoagulation proved to be safe, even in patients with cerebral hemorrhage.
Einhäupl K, Stam J, Bousser MG, De Bruijn SF, Ferro JM, Martinelli I, Masuhr F; European Federation of Neurological Societies.
EFNS guideline on the treatment of cerebral venous and sinus thrombosis in adult patients.
Eur J Neurol. 2010 Oct;17(10):1229-35. doi: 10.1111/j.1468-1331.2010.03011.x.
Abstract/Text
BACKGROUND: Cerebral venous and sinus thrombosis (CVST) is a rather rare disease which accounts for <1% of all strokes. Diagnosis is still frequently overlooked or delayed as a result of the wide spectrum of clinical symptoms and the often subacute or lingering onset. Current therapeutic measures which are used in clinical practice include the use of anticoagulants such as dose-adjusted intravenous heparin or body weight-adjusted subcutaneous low-molecular-weight heparin (LMWH), the use of thrombolysis and symptomatic therapy including control of seizures and elevated intracranial pressure.
METHODS: We searched MEDLINE (National Library of Medicine), the Cochrane Central Register of Controlled Trials (CENTRAL) and the Cochrane Library to review the strength of evidence to support these interventions and the preparation of recommendations on the therapy of CVST based on the best available evidence. Review articles and book chapters were also included. Recommendations were reached by consensus. Where there was a lack of evidence but consensus was clear we stated our opinion as good practice points.
RESULTS AND CONCLUSIONS: Patients with CVST without contraindications for anticoagulation (AC) should be treated either with body weight-adjusted subcutaneous LMWH or with dose-adjusted intravenous heparin (level B recommendation). Concomitant intracranial haemorrhage (ICH) related to CVST is not a contraindication for heparin therapy. The optimal duration of oral anticoagulant therapy after the acute phase is unclear. Oral AC may be given for 3 months if CVST was secondary to a transient risk factor, for 6-12 months in patients with idiopathic CVST and in those with "mild" thrombophilia, such as heterozygous factor V Leiden or prothrombin G20210A mutation and high plasma levels of factor VIII. Indefinite AC should be considered in patients with recurrent episodes of CVST and in those with one episode of CVST and 'severe' thrombophilia, such as antithrombin, protein C or protein S deficiency, homozygous factor V Leiden or prothrombin G20210A mutation, antiphospholipid antibodies and combined abnormalities (good practice point). There is insufficient evidence to support the use of either systemic or local thrombolysis in patients with CVST. If patients deteriorate despite adequate AC and other causes of deterioration have been ruled out, thrombolysis may be a therapeutic option in selected cases, possibly in those without large ICH and threatening herniation (good practice point). There are no controlled data about the risks and benefits of certain therapeutic measures to reduce an elevated intracranial pressure (with brain displacement) in patients with severe CVST. However, in severe cases with impending herniation craniectomy can be used as a life-saving intervention (good practice point).
© 2010 The Author(s). European Journal of Neurology © 2010 EFNS.
Stam J, De Bruijn SF, DeVeber G.
Anticoagulation for cerebral sinus thrombosis.
Cochrane Database Syst Rev. 2002;(4):CD002005. doi: 10.1002/14651858.CD002005.
Abstract/Text
BACKGROUND: Treatment of cerebral sinus thrombosis with anticoagulants has been controversial. Anticoagulants may prevent new venous infarcts, neurologic deterioration, and pulmonary embolism but may also promote haemorrhages.
OBJECTIVES: To review the available evidence regarding the effectiveness and safety of anticoagulant therapy in patients with confirmed cerebral sinus thrombosis.
SEARCH STRATEGY: We searched the Cochrane Stroke Group Trials Register (last searched 18 March 2002). We also searched MEDLINE (1966-Oct 2001), EMBASE (1980-Feb 2002) and the Cochrane Controlled Trials Register (Cochrane Library, 2002 Issue 1) and contacted authors to identify additional published and unpublished studies.
SELECTION CRITERIA: Unconfounded randomised controlled trials in which anticoagulant therapy was compared with placebo or open control in patients with cerebral sinus thrombosis (confirmed by intra-arterial contrast or magnetic resonance angiography).
DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted outcomes for each of the two treatment groups (anticoagulant treatment and control). The outcome data for each patient are analysed in the treatment group to which the patient was originally allocated ('intention to treat' analysis). A weighted estimate of the treatment effects across trials (relative risk, absolute risk reduction) is calculated using the Cochrane statistical software.
MAIN RESULTS: Two small trials involving 79 patients fulfilled the inclusion criteria. One trial (20 patients) examined the efficacy of intravenous, adjusted dose unfractionated heparin. The other trial (59 patients) examined high dose, body weight adjusted, subcutaneous, low-molecular weight heparin (Nadroparin). Anticoagulant therapy was associated with a pooled relative risk of death of 0.33 (95 % CI 0.08 to 1.21) and of death or dependency of 0.46 (95 % CI 0.16 to 1.31). No new symptomatic intracerebral haemorrhages were observed. One major gastro-intestinal haemorrhage occurred after anticoagulant treatment. Two control patients (placebo) had a diagnosis of probable pulmonary embolism (one fatal).
REVIEWER'S CONCLUSIONS: Based upon the limited evidence available, anticoagulant treatment for cerebral sinus thrombosis appeared to be safe and was associated with a potentially important reduction in the risk of death or dependency which did not reach statistical significance.
日本脳卒中学会 脳卒中ガイドライン委員会 編：脳卒中治療ガイドライン2021[改訂2023]．協和企画、2023.
Coutinho J, de Bruijn SF, Deveber G, Stam J.
Anticoagulation for cerebral venous sinus thrombosis.
Cochrane Database Syst Rev. 2011 Aug 10;2011(8):CD002005. doi: 10.1002/14651858.CD002005.pub2. Epub 2011 Aug 10.
Abstract/Text
BACKGROUND: Treatment of cerebral venous sinus thrombosis with anticoagulants has been controversial. Anticoagulants may prevent new venous infarcts, neurologic deterioration and pulmonary embolism but may also promote haemorrhages.
OBJECTIVES: To assess the effectiveness and safety of anticoagulant therapy in patients with confirmed cerebral venous sinus thrombosis.
SEARCH STRATEGY: We searched the Cochrane Stroke Group Trials Register (last searched August 2010), MEDLINE (1950 to August 2010), EMBASE (1980 to August 2010) and the Cochrane Central Register of Controlled Trials (The Cochrane Library, 2011 Issue 1). In an effort to identify further published, unpublished and ongoing trials we searched ongoing trials registers and reference lists of relevant articles, and contacted authors.
SELECTION CRITERIA: Unconfounded randomised controlled trials in which anticoagulant therapy was compared with placebo or open control in patients with cerebral venous sinus thrombosis (confirmed by intra-arterial contrast, or venography with magnetic resonance, or venography with computed tomography imaging).
DATA COLLECTION AND ANALYSIS: Two review authors independently extracted outcomes for each of the two treatment groups (anticoagulant treatment and control). The outcome data for each patient were analysed in the treatment group to which the patient was originally allocated (intention-to-treat analysis). We calculated a weighted estimate of the treatment effects across trials (relative risk, absolute risk reduction).
MAIN RESULTS: We included two small trials involving 79 patients. One trial (20 patients) examined the efficacy of intravenous, adjusted dose unfractionated heparin. The other trial (59 patients) examined high dose, body weight adjusted, subcutaneous, low-molecular weight heparin (nadroparin). Anticoagulant therapy was associated with a pooled relative risk of death of 0.33 (95% confidence interval (CI) 0.08 to 1.21) and of death or dependency of 0.46 (95% CI 0.16 to 1.31). The absolute reduction in the risk of death or dependency was 13% (95% CI 30% to -3%). No new symptomatic intracerebral haemorrhages were observed. One major gastro-intestinal haemorrhage occurred after anticoagulant treatment. Two control patients (placebo) had a diagnosis of probable pulmonary embolism (one fatal).
AUTHORS' CONCLUSIONS: Based upon the limited evidence available, anticoagulant treatment for cerebral venous sinus thrombosis appeared to be safe and was associated with a potentially important reduction in the risk of death or dependency which did not reach statistical significance.
Wingerchuk DM, Wijdicks EF, Fulgham JR.
Cerebral venous thrombosis complicated by hemorrhagic infarction: factors affecting the initiation and safety of anticoagulation.
Cerebrovasc Dis. 1998 Jan-Feb;8(1):25-30. doi: 10.1159/000015811.
Abstract/Text
BACKGROUND AND PURPOSE: Anticoagulation (AC) may improve outcome in cerebral venous thrombosis (CVT), even when complicated by pretreatment hemorrhagic infarction (HI). The HI characteristics which affect the decision to initiate AC therapy and its outcome are unknown. We reviewed our experience with AC treatment for patients with CVT and HI.
METHODS: Retrospective study.
RESULTS: Two groups of patients were compared: those who received AC (n = 6) and those who did not (n = 6). Hemorrhage volumes ranged from petechial to large (93 cm3) hematoma with mass effect. Anticoagulated patients received treatment a mean of 11.3 days after symptom onset. Each had exclusively extratemporal HI without midline shift and had stable hemorrhage volumes and clinical status for at least 24 h prior to AC. AC did not increase HI volume or worsen clinical outcome. All 6 non-AC patients had enlarging hematomas. Four of these 6 patients had temporal HI; and two required hematoma resection.
CONCLUSIONS: AC therapy was avoided in CVT patients with HI that were located in the temporal lobe, caused midline shift or were enlarging. AC was safely initiated within several days in clinically stable patients with non-temporal-lobe HI of unchanging volume. We suggest that the location and unchanged volume on serial CT may be important factors influencing the safety of AC therapy in patients with CVT and HI.
Canhão P, Falcão F, Ferro JM.
Thrombolytics for cerebral sinus thrombosis: a systematic review.
Cerebrovasc Dis. 2003;15(3):159-66. doi: 10.1159/000068833.
Abstract/Text
BACKGROUND AND PURPOSE: The use of thrombolytics is frequently mentioned in patients with cerebral venous or dural sinus thrombosis (CVDST) who deteriorate despite anticoagulant therapy. The aim of this review was to collect all the published information about their use in CVDST and to assess their efficacy and safety.
METHODS: To find cases of CVDST treated with thrombolytics, we performed a MEDLINE search from 1966 to July 2001, checked all reference lists of studies found and hand searched volumes of 11 journals. Data was extracted by means of a standardised data extraction form. Proportions and 95% confidence intervals (CI) were calculated for outcomes and complications of thrombolytics. Cases were stratified according to variables that may influence the outcome and subgroups were compared by odds ratios and 95% CI.
RESULTS: No randomised clinical trial (RCT) was found. Seventy-two studies (169 patients) were included. Urokinase was the thrombolytic most frequently administered (76%). In the majority of cases the thrombolytic was locally infused in the occluded sinus (88%). At discharge, 10 cases (7%; 95% CI 3-12%) were dependent and 9 cases (5%; 95% CI 2-9%) died. Intracranial haemorrhages occurred in 17% of cases. In 5% they were associated with clinical deterioration. Extracranial haemorrhages occurred in 21%, but only 2% required blood transfusion.
CONCLUSIONS: Thrombolytics appeared to be reasonably safe in CVDST, but its efficacy cannot be assessed from the published data. Considering that CVDST is an uncommon disease, a randomised controlled trial to assess effectiveness and safety of local thrombolytics in cases of CVDST with poor prognosis is difficult but not impossible to undertake, on a multicentre international collaboration trial.
Copyright 2003 S. Karger AG, Basel
Ciccone A, Canhão P, Falcão F, Ferro JM, Sterzi R.
Thrombolysis for cerebral vein and dural sinus thrombosis.
Cochrane Database Syst Rev. 2004;2004(1):CD003693. doi: 10.1002/14651858.CD003693.pub2.
Abstract/Text
BACKGROUND: Treatment of cerebral sinus thrombosis with thrombolytics has been reported in cases with a deteriorating clinical course despite anticoagulant therapy. The rationale of this treatment is to promote rapid recanalisation of the occluded sinus.
OBJECTIVES: To review the available evidence on the efficacy and safety of thrombolysis in confirmed cerebral sinus thrombosis.
SEARCH STRATEGY: We searched the Cochrane Stroke Group trials register (March 2003), the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 1, 2003), MEDLINE (1966 to March 2003), EMBASE (1980 to March 2003), and reference lists of all relevant publications.
SELECTION CRITERIA: We aimed to analyse separately unconfounded randomised controlled trials comparing thrombolytic agent with placebo, or thrombolytic agent with antithrombotic therapy, or thrombolytic agent and antithrombotic with antithrombotic alone, in patients with dural sinus thrombosis (confirmed by MR venography, intra-arterial venography or CT venography).
DATA COLLECTION AND ANALYSIS: Two groups of reviewers independently applied the inclusion criteria.
MAIN RESULTS: No randomised controlled trials were found.
REVIEWER'S CONCLUSIONS: There is currently no available evidence from randomised controlled trials regarding the efficacy or safety of thrombolytic therapy in dural sinus thrombosis. A randomised controlled trial is justified to test this therapy especially in patients predicted to have a poor prognosis.
Frey JL, Muro GJ, McDougall CG, Dean BL, Jahnke HK.
Cerebral venous thrombosis: combined intrathrombus rtPA and intravenous heparin.
Stroke. 1999 Mar;30(3):489-94. doi: 10.1161/01.str.30.3.489.
Abstract/Text
BACKGROUND AND PURPOSE: We chose to evaluate the safety and efficacy of combined intrathrombus rtPA and intravenous heparin in cerebral venous thrombosis (CVT).
METHODS: We treated 12 patients with symptoms of 1 to 40 days' duration (eg, headache, somnolence, focal deficits, seizures, and nausea and vomiting). Pretreatment MRI disclosed subtle hemorrhagic venous infarction in 4 patients, obvious hemorrhagic infarction in 2, small parenchymal hemorrhage from recent pallidotomy in 1, and no focal lesion in 5. Magnetic resonance venography and contrast venography identified thrombi in the superior sagittal sinus (SSS) in 3 patients; transverse/sigmoid sinus (TS/SS) in 2; SSS and both TS/SS in 1; SSS and 1 TS/SS in 5; and SSS, 1 TS/SS, and straight sinus in 1 patient. A loading dose of rtPA was instilled throughout the clot at 1 mg/cm, followed by continuous intrathrombus infusion at 1 to 2 mg/h. Intravenous heparin was infused concomitantly.
RESULTS: Flow was restored completely in 6 patients and partially in 3, with a mean rtPA dose of 46 mg (range, 23 to 128 mg) at a mean time of 29 hours (range, 13 to 77 hours). Symptoms improved in these 9 patients concomitantly with flow restoration. Flow could not be restored in 3 patients. In 1 of them, treatment was stopped when little progress had been made, and fibrinogen level dropped to 118 mg/dL. In the other 2 patients, hemorrhagic worsening occurred, and treatment was abbreviated after initial rtPA dosing. In 1 of these, the hematoma was evacuated.
CONCLUSIONS: Our experience with intrathrombus rtPA in conjunction with intravenous heparin in patients with CVT is encouraging. This therapy should probably be regarded as unsafe in patients with obvious hemorrhage. Time to restore flow may be faster than with urokinase (an average of 71 hours has been reported for 29 documented patients). Further evaluation of rtPA with heparin in CVT is warranted.
Lee SK, Mokin M, Hetts SW, Fifi JT, Bousser MG, Fraser JF; Society of NeuroInterventional Surgery.
Current endovascular strategies for cerebral venous thrombosis: report of the SNIS Standards and Guidelines Committee.
J Neurointerv Surg. 2018 Aug;10(8):803-810. doi: 10.1136/neurintsurg-2018-013973. Epub 2018 Jun 5.
Abstract/Text
Coutinho JM, Zuurbier SM, Bousser MG, Ji X, Canhão P, Roos YB, Crassard I, Nunes AP, Uyttenboogaart M, Chen J, Emmer BJ, Roosendaal SD, Houdart E, Reekers JA, van den Berg R, de Haan RJ, Majoie CB, Ferro JM, Stam J; TO-ACT investigators.
Effect of Endovascular Treatment With Medical Management vs Standard Care on Severe Cerebral Venous Thrombosis: The TO-ACT Randomized Clinical Trial.
JAMA Neurol. 2020 Aug 1;77(8):966-973. doi: 10.1001/jamaneurol.2020.1022.
Abstract/Text
IMPORTANCE: To date, only uncontrolled studies have evaluated the efficacy and safety of endovascular treatment (EVT) in patients with cerebral venous thrombosis (CVT), leading to the lack of recommendations on EVT for CVT.
OBJECTIVE: To evaluate the efficacy and safety of EVT in patients with a severe form of CVT.
DESIGN, SETTING, AND PARTICIPANTS: TO-ACT (Thrombolysis or Anticoagulation for Cerebral Venous Thrombosis) was a multicenter, open-label, blinded end point, randomized clinical trial conducted in 8 hospitals in 3 countries (the Netherlands, China, and Portugal). Patients were recruited from September 2011 to October 2016, and follow-up began in March 2012 and was completed in December 2017. Adult patients with radiologically confirmed CVT who had at least 1 risk factor for a poor outcome (mental status disorder, coma state, intracerebral hemorrhage, or thrombosis of the deep venous system) were included. Data were analyzed according to the intention-to-treat principle from March 2018 to February 2019. The trial was halted after the first interim analysis for reasons of futility.
INTERVENTIONS: Patients were randomized to receive either EVT with standard medical care (intervention group) or guideline-based standard medical care only (control group). The EVT consisted of mechanical thrombectomy, local intrasinus application of alteplase or urokinase, or a combination of both strategies. Patients in the intervention group underwent EVT as soon as possible but no later than 24 hours after randomization.
MAIN OUTCOMES AND MEASURES: Primary end point was the proportion of patients with a good outcome at 12 months (recovered without a disability; modified Rankin Scale [mRS] score of 0-1). Secondary end points were the proportion of patients with an mRS score of 0 to 1 at 6 months and an mRS score of 0 to 2 at 6 and 12 months, outcome on the mRS across the ordinal continuum at 12 months, recanalization rate, and surgical interventions in relation to CVT. Safety end points included symptomatic intracranial hemorrhage.
RESULTS: Of the 67 patients enrolled and randomized, 33 (49%) were randomized to the intervention group and 34 (51%) were randomized to the control group. Patients in the intervention group vs those in the control group were slightly older (median [interquartile range (IQR)] age, 43 [33-50] years vs 38 [23-48] years) and comprised fewer women (23 women [70%] vs 27 women [79%]). The median (IQR) baseline National Institutes of Health Stroke Scale score was 12 (7-20) in the EVT group and 12 (5-20) in the standard care group. At the 12-month follow-up, 22 intervention patients (67%) had an mRS score of 0 to 1 compared with 23 control patients (68%) (relative risk ratio, 0.99; 95% CI, 0.71-1.38). Mortality was not statistically significantly higher in the EVT group (12% [n = 4] vs 3% [n = 1]; P = .20). The frequency of symptomatic intracerebral hemorrhage was not statistically significantly lower in the intervention group (3% [n = 1] vs 9% [n = 3]; P = .61).
CONCLUSIONS AND RELEVANCE: The TO-ACT trial showed that EVT with standard medical care did not appear to improve functional outcome of patients with CVT. Given the small sample size, the possibility exists that future studies will demonstrate better recovery rates after EVT for this patient population.
TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01204333.
日本脳卒中学会 脳卒中ガイドライン委員会 編：脳卒中治療ガイドライン2021．協和企画、2021.
de Freitas GR, Bogousslavsky J.
Risk factors of cerebral vein and sinus thrombosis.
Front Neurol Neurosci. 2008;23:23-54. doi: 10.1159/000111259.
Abstract/Text
The risk factors for deep venous thrombosis (and for cerebral vein and sinus thrombosis, CVST) differ from those for arterial disease. The risk factors for venous thrombosis are linked to the Virchow triad of stasis of the blood, changes in the vessel wall, and changes in the composition of the blood, especially the first and third of these. Risk factors are usually divided into acquired (e.g. surgery, trauma, pregnancy, puerperium, lupus anticoagulant, malignant disease, and female hormones) and genetic (congenital thrombophilia). However, the separation of genetic and acquired risk factors is somewhat artificial, since they have additive effects and venous thrombosis is often multifactorial. In this review, we discuss acquired risk factors for CVST. These include hormonal changes (e.g. oral contraceptives use, hormone replacement therapy, pregnancy and puerperium), mechanical precipitants (e.g. head trauma, jugular catheterization, surgery, lumbar puncture), local and generalized infections, cancer, acquired prothrombotic states (e.g. hyperhomocysteinemia, nephrotic syndrome), inflammatory diseases (e.g. vaculitis, intestinal inflammatory disease), hematological disorders, neurological diseases (e.g. dural arteriovenous malformations, spontaneous intracranial hypotension), drugs and other situations. However, only some conditions are consistently present in case series, while many appear only in anecdotal reports. Thus, in most situations, a causal link cannot be established. Determining a cause-and-effect relationship is essential for developing preventive, diagnostic, and therapeutic strategies. Therefore, further multicentered, case-controlled studies are crucial for better understanding the pathogenesis of CVST.
日本脳卒中学会/日本血栓止血学会：ワクチン接種後の血小板減少症を伴う血栓症の診断と治療の手引き・第4版 [Internet]. Available from: https://www.jsth.org/wordpress/wp-content/uploads/2022/07/COVID-19-ワクチン接種後の-血小板減少症を伴う血栓症の診断と治療の手引き・第4版.pdf
Ferro JM, Crassard I, Coutinho JM, Canhão P, Barinagarrementeria F, Cucchiara B, Derex L, Lichy C, Masjuan J, Massaro A, Matamala G, Poli S, Saadatnia M, Stolz E, Viana-Baptista M, Stam J, Bousser MG; Second International Study on Cerebral Vein and Dural Sinus Thrombosis (ISCVT 2) Investigators.
Decompressive surgery in cerebrovenous thrombosis: a multicenter registry and a systematic review of individual patient data.
Stroke. 2011 Oct;42(10):2825-31. doi: 10.1161/STROKEAHA.111.615393. Epub 2011 Jul 28.
Abstract/Text
BACKGROUND AND PURPOSE: Herniation attributable to unilateral mass effect is the major cause of death in cerebral venous thrombosis (CVT). Decompressive surgery may be lifesaving in these patients.
METHODS: Retrospective registry of cases of acute CVT treated with decompressive surgery (craniectomy or hematoma evacuation) in 22 centers and systematic review of all published cases of CVT treated with decompressive surgery. The primary outcome was the score on the modified Rankin Scale (mRS) score at last follow-up, dichotomized between favorable (mRS score, 0-4) and unfavorable outcome (mRS score, 5 or death). Secondary outcomes were complete recovery (mRS score 0-1), independence (mRS score, 0-2), severe dependence (mRS score, 4-5), and death at last available follow-up.
RESULTS: Sixty-nine patients were included and 38 were from the registry. Decompressive craniectomy was performed in 45 patients, hematoma evacuation was performed in 7, and both interventions were performed in 17 patients. At last follow-up (median, 12 months) only 12 (17.4%) had un unfavorable outcome. Twenty-six (37.7%) had mRS score 0 to 1, 39 (56.5%) had mRS score 0 to 2, 4 (5.8%) were alive with mRS score 4 to 5, and 11 (15.9%) patients died. Three of the 9 patients with bilateral fixed pupils recovered completely. Comatose patients were less likely to be independent (mRS score 0-2) than noncomatose patients (45% versus 84%; P=0.003). Patients with bilateral lesions were more likely to have unfavorable outcomes (50% versus 11%; P=0.004) and to die (42% versus 11%; P=0.025).
CONCLUSIONS: In CVT patients with large parenchymal lesions causing herniation, decompressive surgery was lifesaving and often resulted in good functional outcome, even in patients with severe clinical conditions.
Kwan J, Guenther A.
Antiepileptic drugs for the primary and secondary prevention of seizures after intracranial venous thrombosis.
Cochrane Database Syst Rev. 2006 Jul 19;(3):CD005501. doi: 10.1002/14651858.CD005501.pub2. Epub 2006 Jul 19.
Abstract/Text
BACKGROUND: Intracranial venous thrombosis (ICVT) commonly presents with seizures in the acute period, and some patients may develop recurrent seizures in the long term. The prophylactic use of antiepileptic drugs (AEDs) for the management of post-ICVT seizures is controversial and there is currently no consensus on the optimal management of post-ICVT seizures.
OBJECTIVES: To assess the effects of AEDs for the primary and secondary prevention of seizures related to ICVT.(1) Do AEDs reduce the likelihood of seizures in patients who have had an ICVT but have not had a seizure?(2) Do AEDs reduce the likelihood of further seizures in patients who have had an ICVT and at least one seizure?
SEARCH STRATEGY: We aimed to identify relevant studies in the Cochrane Epilepsy Group and Cochrane Stroke Group Trials Registers. We also undertook specialised searches of the Cochrane Central Register of Controlled Trials (CENTRAL) and MEDLINE, and checked the reference lists of articles retrieved from the searches.
SELECTION CRITERIA: We considered all randomised and quasi-randomised controlled trials in which patients were assigned to a treatment group (that is, receiving at least one AED) or control group (receiving placebo or no drug).
DATA COLLECTION AND ANALYSIS: Both review authors independently screened and assessed the methodological quality of the studies. If studies had been included, then one review author would have extracted the data and the other would have checked the extracted data.
MAIN RESULTS: No relevant studies were found.
AUTHORS' CONCLUSIONS: There is no evidence to support or refute the use of antiepileptic drugs for the primary or secondary prevention of seizures related to intracranial venous thrombosis. Well-designed randomised controlled trials are urgently needed to inform practice.
Ferro JM, Coutinho JM, Dentali F, Kobayashi A, Alasheev A, Canhão P, Karpov D, Nagel S, Posthuma L, Roriz JM, Caria J, Frässdorf M, Huisman H, Reilly P, Diener HC; RE-SPECT CVT Study Group.
Safety and Efficacy of Dabigatran Etexilate vs Dose-Adjusted Warfarin in Patients With Cerebral Venous Thrombosis: A Randomized Clinical Trial.
JAMA Neurol. 2019 Dec 1;76(12):1457-1465. doi: 10.1001/jamaneurol.2019.2764.
Abstract/Text
IMPORTANCE: Patients with cerebral venous thrombosis (CVT) are at risk of recurrent venous thrombotic events (VTEs). Non-vitamin K oral anticoagulants have not been evaluated in randomized controlled trials in CVT.
OBJECTIVE: To compare the efficacy and safety of dabigatran etexilate with those of dose-adjusted warfarin in preventing recurrent VTEs in patients who have experienced a CVT.
DESIGN, SETTING, AND PARTICIPANTS: RE-SPECT CVT is an exploratory, prospective, randomized (1:1), parallel-group, open-label, multicenter clinical trial with blinded end-point adjudication (PROBE design). It was performed from December 21, 2016, to June 22, 2018, with a follow-up of 25 weeks, at 51 tertiary sites in 9 countries (France, Germany, India, Italy, the Netherlands, Poland, Portugal, Russia, and Spain). Adult consecutive patients with acute CVT, who were stable after 5 to 15 days of treatment with parenteral heparin, were screened for eligibility. Patients with CVT associated with central nervous system infection or major trauma were excluded, but those with intracranial hemorrhage from index CVT were allowed to participate. After exclusions, 120 patients were randomized. Data were analyzed following the intention-to-treat approach.
INTERVENTIONS: Dabigatran, 150 mg twice daily, or dose-adjusted warfarin for a treatment period of 24 weeks.
MAIN OUTCOMES AND MEASURES: Primary outcome was a composite of patients with a new VTE (recurrent CVT, deep vein thrombosis of any limb, pulmonary embolism, and splanchnic vein thrombosis) or major bleeding during the study period. Secondary outcomes were cerebral venous recanalization and clinically relevant non-major bleeding events.
RESULTS: In total, 120 patients with CVT were randomized to the 2 treatment groups (60 to dabigatran and 60 to dose-adjusted warfarin). Of the randomized patients, the mean (SD) age was 45.2 (13.8) years, and 66 (55.0%) were women. The mean (SD) duration of exposure was 22.3 (6.16) weeks for the dabigatran group and 23.0 (5.20) weeks for the warfarin group. No recurrent VTEs were observed. One (1.7%; 95% CI, 0.0-8.9) major bleeding event (intestinal) was recorded in the dabigatran group, and 2 (3.3%; 95% CI, 0.4-11.5) (intracranial) in the warfarin group. One additional patient (1.7; 95% CI, 0.0-8.9) in the warfarin group experienced a clinically relevant non-major bleeding event. Recanalization occurred in 33 patients in the dabigatran group (60.0%; 95% CI, 45.9-73.0) and in 35 patients in the warfarin group (67.3%; 95% CI, 52.9-79.7).
CONCLUSIONS AND RELEVANCE: This trial found that patients who had CVT anticoagulated with either dabigatran or warfarin had low risk of recurrent VTEs, and the risk of bleeding was similar with both medications, suggesting that both dabigatran and warfarin may be safe and effective for preventing recurrent VTEs in patients with CVT.
TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02913326.
Maqsood M, Imran Hasan Khan M, Yameen M, Aziz Ahmed K, Hussain N, Hussain S.
Use of oral rivaroxaban in cerebral venous thrombosis.
J Drug Assess. 2020 Dec 2;10(1):1-6. doi: 10.1080/21556660.2020.1838769. Epub 2020 Dec 2.
Abstract/Text
BACKGROUND: Cerebral venous thrombosis (CVT) is an uncommon cause of stroke in humans and the mainstay of treatment is anticoagulation unless contraindicated. Non-vitamin K oral anticoagulants have not been duly evaluated in randomized controlled trials in CVT.
OBJECTIVE: To compare the efficacy and safety of oral rivaroxaban with vitamin K anticoagulant (warfarin) in preventing recurrent venous thromboembolism (VTE) in patients with CVT.
METHODS: Adult patients with CVT, who were stable after 5-12 days of treatment with parenteral heparin 1 mg/kg, were screened for eligibility. The patients were randomly divided into two groups to receive oral rivaroxaban 20-30 mg daily or warfarin 1, 3 or 5 mg daily (with the dose adjusted to maintain an INR of 2-3), for 3-12 months. Recanalization rates, periprocedural complications, and clinical outcomes were assessed by Magnetic Resonance Venography (MRV) and National Institutes of Health Stroke Scale (NIHSS) at 3rd, 6th and 12th month follow-ups.
RESULTS: In total, 45 patients with CVT were randomized to the two treatment groups (21 to rivaroxaban and 24 to warfarin). Overall recanalization was achieved by 18 (86%) and 20 (83%) cases from rivaroxaban and warfarin group, respectively at 6th month follow-up; and by all 45 (100%) cases from the both groups at 12th month follow-up. Excellent outcome (NIHSS score 0) was obtained by 20 (95%) cases from rivaroxaban group at 3rd to 12th month follow-ups; and by 23 (96%) cases at 6th to 12th month follow-ups. There were no major bleeding events during the trial. None of the patients developed recurrence of thrombosis. Statistically, no significant difference between the two treatment groups in terms of recanalization and clinical outcomes could be observed.
CONCLUSION: Rivaroxaban is a safe option in CVT however; larger randomized controlled studies will impact the results validity.
© 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
Khorvash F, Farajpour-Khanaposhtani MJ, Hemasian H, Saadatnia SM.
Evaluation of rivaroxaban versus warfarin for the treatment of cerebral vein thrombosis: A case-control blinded study.
Curr J Neurol. 2021 Jul 6;20(3):125-130. doi: 10.18502/cjn.v20i3.7687.
Abstract/Text
Background: Anticoagulation therapy following cerebral vein thrombosis (CVT) can improve mortality and morbidity. Vitamin K antagonists are currently the routine oral anticoagulant used for CVT; while by introduction of rivaroxaban, a direct factor Xa inhibitor, the attentions have been deviated toward novel agents, but the evidence is not strong. The current study is aimed to compare the efficacy and safety of rivaroxaban versus warfarin for anticoagulation therapy of CVT. Methods: The current randomized clinical trial has been conducted on 50 patients with CVT among which, 25 ones were randomly allocated to rivaroxaban treatment (20 mg per day for three months) and remained 25 ones to warfarin treatment [adjusted based on international normalized ratio (INR) of 2-3]. The Modified Rankin Scale (mRS) and clinical investigations, including the incidence of seizure, papilledema, intra/extra-cranial bleeding, blurred vision, headache, nausea and vomiting, and death were evaluated at discharge time and within 3 and 6 months following CVT incidence; eventually, two groups were compared. Results: Comparison of mRS scores between the groups revealed significant differences in none of the interval assessments, at the time of admission (P = 0.510), within three months (P = 0.630), and within six months (P = 0.990), while both of the approaches led to significant decrease in mRS scores following both of the treatments (P < 0.001). The comparison of drug-related adverse effects showed insignificant difference between warfarin versus rivaroxaban (P > 0.050). Conclusion: Based on this study, rivaroxaban is an efficacious agent for the treatment of CVT without remarkable adverse effects.
Copyright © 2021 Iranian Neurological Association, and Tehran University of Medical Sciences. Published by Tehran University of Medical Sciences.
Yaghi S, Shu L, Bakradze E, Salehi Omran S, Giles JA, Amar JY, Henninger N, Elnazeir M, Liberman AL, Moncrieffe K, Lu J, Sharma R, Cheng Y, Zubair AS, Simpkins AN, Li GT, Kung JC, Perez D, Heldner M, Scutelnic A, Seiffge D, Siepen B, Rothstein A, Khazaal O, Do D, Kasab SA, Rahman LA, Mistry EA, Kerrigan D, Lafever H, Nguyen TN, Klein P, Aparicio H, Frontera J, Kuohn L, Agarwal S, Stretz C, Kala N, El Jamal S, Chang A, Cutting S, Xiao H, de Havenon A, Muddasani V, Wu T, Wilson D, Nouh A, Asad SD, Qureshi A, Moore J, Khatri P, Aziz Y, Casteigne B, Khan M, Cheng Y, Mac Grory B, Weiss M, Ryan D, Vedovati MC, Paciaroni M, Siegler JE, Kamen S, Yu S, Leon Guerrero CR, Atallah E, De Marchis GM, Brehm A, Dittrich T, Psychogios M, Alvarado-Dyer R, Kass-Hout T, Prabhakaran S, Honda T, Liebeskind DS, Furie K.
Direct Oral Anticoagulants Versus Warfarin in the Treatment of Cerebral Venous Thrombosis (ACTION-CVT): A Multicenter International Study.
Stroke. 2022 Mar;53(3):728-738. doi: 10.1161/STROKEAHA.121.037541. Epub 2022 Feb 10.
Abstract/Text
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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).
CONCLUSIONS: 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.
Yaghi S, Saldanha IJ, Misquith C, Zaidat B, Shah A, Joudi K, Persaud B, Abdul Khalek F, Shu L, de Havenon A, Mistry EA, Bakradze E, Goldstein ED, Reagan J, Theodorou A, Palaiodimou L, Furie K, Field TS, Tsivgoulis G, Mac Grory B.
Direct Oral Anticoagulants Versus Vitamin K Antagonists in Cerebral Venous Thrombosis: A Systematic Review and Meta-Analysis.
Stroke. 2022 Oct;53(10):3014-3024. doi: 10.1161/STROKEAHA.122.039579. Epub 2022 Aug 8.
Abstract/Text
BACKGROUND: High level evidence for direct oral anticoagulants (DOACs) in patients with cerebral venous thrombosis is lacking. We performed a systematic review and meta-analysis to assess the efficacy and safety of DOACs versus vitamin K antagonists in patients with cerebral venous thrombosis.
METHODS: This systematic review was registered in PROSPERO (CRD42021228800). We searched MEDLINE (via Ovid), EMBASE, CINAHL, and the Web of Science Core Collection between January 1, 2007 and Feb 22, 2022. Search terms included a combination of keywords and controlled vocabulary terms for cerebral venous thrombosis, vitamin K antagonists/warfarin, and DOACs. We included both randomized and nonrandomized studies that compared vitamin K antagonists and DOACs in 5 or more patients with cerebral venous thrombosis. Where studies were sufficiently similar, we performed meta-analyses for efficacy (recurrent venous thromboembolism and complete recanalization) and safety (major hemorrhage) outcomes, using relative risks (RRs).
RESULTS: Out of 10 665 records identified, we screened 254 as potentially eligible. Nineteen studies (16 observational studies [n=1735] and 3 randomized controlled trials [n=215]) met the inclusion criteria. All 3 randomized controlled trials had some concerns, and all 16 observational studies had at least moderate risk of bias. When compared with vitamin K antagonist treatment, DOAC had comparable risks of recurrent venous thromboembolism (relative risk [RR], 0.85 [95% CI, 0.52-1.37], I2=0%), major hemorrhage (RR, 0.70 [95% CI, 0.40-1.21], I2=0%), intracranial hemorrhage (RR, 0.58 [95% CI, 0.30-1.12]; I2=0%), death (RR, 1.14 [95% CI, 0.54-2.43], I2=1%), and complete venous recanalization (RR, 0.98 [95% CI, 0.87-1.11]; I2=0%).
CONCLUSIONS: This systematic review and meta-analysis suggest that in patients with cerebral venous thrombosis, DOACs, and warfarin may have comparable efficacy and safety. Given the limitations of the studies included (low number of randomized controlled trials, modest total sample size, rare outcome events), our findings should be interpreted with caution pending confirmation by ongoing randomized controlled trials and large, prospective, observational studies.
Field TS, Dizonno V, Almekhlafi MA, Bala F, Alhabli I, Wong H, Norena M, Villaluna MK, King-Azote P, Ratnaweera N, Mancini S, Van Gaal SC, Wilson LK, Graham BR, Sposato LA, Blacquiere D, Dewar BM, Boulos MI, Buck BH, Odier C, Perera KS, Pikula A, Tkach A, Medvedev G, Canfield C, Mortenson WB, Nadeau JO, Alshimemeri S, Benavente OR, Demchuk AM, Dowlatshahi D, Lanthier S, Lee AYY, Mandzia J, Suryanarayan D, Weitz JI, Hill MD; SECRET Investigators.
Study of Rivaroxaban for Cerebral Venous Thrombosis: A Randomized Controlled Feasibility Trial Comparing Anticoagulation With Rivaroxaban to Standard-of-Care in Symptomatic Cerebral Venous Thrombosis.
Stroke. 2023 Nov;54(11):2724-2736. doi: 10.1161/STROKEAHA.123.044113. Epub 2023 Sep 7.
Abstract/Text
BACKGROUND: Emerging data suggest that direct oral anticoagulants may be a suitable choice for anticoagulation for cerebral venous thrombosis (CVT). However, conducting high-quality trials in CVT is challenging as it is a rare disease with low rates of adverse outcomes such as major bleeding and functional dependence. To facilitate the design of future CVT trials, SECRET (Study of Rivaroxaban for Cerebral Venous Thrombosis) assessed (1) the feasibility of recruitment, (2) the safety of rivaroxaban compared with standard-of-care anticoagulation, and (3) patient-centered functional outcomes.
METHODS: This was a phase II, prospective, open-label blinded-end point 1:1 randomized trial conducted at 12 Canadian centers. Participants were aged ≥18 years, within 14 days of a new diagnosis of symptomatic CVT, and suitable for oral anticoagulation; they were randomized to receive rivaroxaban 20 mg daily, or standard-of-care anticoagulation (warfarin, target international normalized ratio, 2.0-3.0, or low-molecular-weight heparin) for 180 days, with optional extension up to 365 days. Primary outcomes were annual rate of recruitment (feasibility); and a composite of symptomatic intracranial hemorrhage, major extracranial hemorrhage, or mortality at 180 days (safety). Secondary outcomes included recurrent venous thromboembolism, recanalization, clinically relevant nonmajor bleeding, and functional and patient-reported outcomes (modified Rankin Scale, quality of life, headache, mood, fatigue, and cognition) at days 180 and 365.
RESULTS: Fifty-five participants were randomized. The rate of recruitment was 21.3 participants/year; 57% of eligible candidates consented. Median age was 48.0 years (interquartile range, 38.5-73.2); 66% were female. There was 1 primary event (symptomatic intracranial hemorrhage), 2 clinically relevant nonmajor bleeding events, and 1 recurrent CVT by day 180, all in the rivaroxaban group. All participants in both arms had at least partial recanalization by day 180. At enrollment, both groups on average reported reduced quality of life, low mood, fatigue, and headache with impaired cognitive performance. All metrics improved markedly by day 180.
CONCLUSIONS: Recruitment targets were reached, but many eligible participants declined randomization. There were numerically more bleeding events in patients taking rivaroxaban compared with control, but rates of bleeding and recurrent venous thromboembolism were low overall and in keeping with previous studies. Participants had symptoms affecting their well-being at enrollment but improved over time.
REGISTRATION: URL: https://www.
CLINICALTRIALS: gov; Unique identifier: NCT03178864.
