3. Prise en charge en phase post-aiguë de la thrombose veineuse cérébrale et soins axés sur la personne

La plupart des personnes présentant une TVC passent à un traitement par anticoagulothérapie orale. Les antagonistes de la vitamine K étaient habituellement recommandés dans les anciennes lignes directrices (Ferro et coll. 2017); cependant, un récent ensemble de données probantes, comprenant trois petits essais randomisés (Connor et coll., 2020; Ferro et coll., 2019; Field et coll., 2023) et une vaste étude observationnelle rétrospective (Yaghi et coll., 2022b) indiquent que, chez certains patients, les AOD peuvent également être appropriés, ce qui est également mentionné dans l’énoncé scientifique mis à jour de l’AHA/ASA sur la TVC (Saposnik et coll., 2024). Dans le cadre de ces études, les marqueurs d’efficacité, y compris les taux de récidive de TVC, de thromboembolie veineuse périphérique et de recanalisation veineuse, sont similaires entre les patients traités par AOD et ceux traités par antagonistes de la vitamine K. Les événements liés à l’innocuité, dont les hémorragies extra-crâniennes et intracrâniennes majeures, ont été globalement rares dans les essais randomisés. La vaste étude rétrospective ACTION-CVT a révélé que les taux d’hémorragie étaient plus faibles chez les patients traités par AOD que chez ceux traités par antagonistes de la vitamine K dans le cadre de leurs soins cliniques systématiques (Yaghi et coll., 2022b).

Les AOD ne sont toutefois pas le traitement de choix pour les patients présentant un diagnostic connu de syndrome des antiphospholipides. Plusieurs petites études comparant les AOD à la warfarine pour la prévention des événements thromboemboliques veineux et artériels chez les personnes atteintes du syndrome des antiphospholipides ont été interrompues prématurément en raison de problèmes d’innocuité liés à un grand nombre d’événements thromboemboliques dans le groupe de patients sous AOD (Pengo et coll., 2018; Woller et coll., 2022). D’autres études ont été achevées et ont obtenu des résultats similaires (Ordi-Ros et coll., 2019).

Les taux d’indépendance fonctionnelle après une TVC sont élevés (85 à 90 %). Cependant, un certain nombre d’études ont révélé des taux élevés de problèmes persistants liés à la cognition, l’humeur, la fatigue et les céphalées ayant des répercussions sur la qualité de vie. Alors que des études rétrospectives font état de taux élevés de symptômes persistants des mois et des années après la TVC (Hiltunen et coll., 2016; Koopman et coll., 2009), les participants et participantes à la récente étude prospective SECRET ont constaté que ces symptômes continuaient à s’atténuer en moyenne sur une année de suivi (Field et coll., 2023). Les convulsions tardives touchent environ 10 % des personnes présentant une TVC (Sánchez van Kammen et coll., 2020).

Les besoins, les objectifs et les parcours des personnes ayant une expérience vécue de la TVC sont très variables. Elles ont mentionné que les approches en matière de prise en charge continue de la TVC et des autres séquelles de la TVC en phase post-aiguë doivent être centrées sur la personne et inclure une équipe interdisciplinaire au besoin. Elles ont aussi mis l’accent sur l’importance d’un soutien continu en matière de santé mentale, ainsi que de la prise en compte des déficiences « invisibles » comme les déficiences cognitives, les troubles de la vision et les céphalées.

Les personnes ayant une expérience vécue ont souligné l’importance de la rétroaction de la part de leur prestataire de soins de santé, tout au long de la réadaptation et du rétablissement, sur les progrès réalisés ainsi que sur les aspects pour lesquels les progrès sont plus lents ou absents. Cette rétroaction leur permet de mieux comprendre leurs déficiences et favorise leur rétablissement après l’AVC. Ces personnes ont également souligné l’importance d’un suivi continu, car les besoins et les objectifs en matière de réadaptation et de rétablissement évoluent au fil du temps. Elles ont rappelé l’utilité du soutien par les pairs, en particulier au sein de groupes de personnes qui sont à des stades de vie semblables et qui ont des expériences communes. Un soutien personnalisé pour le retour au travail ou à l’école est très important pour les personnes ayant une expérience vécue. Les personnes présentant une TVC ont également mis l’accent sur l’importance du soutien et de l’information pour les membres de la famille et les aidants et aidantes.

1. Des initiatives de promotion de la santé contribuant à la prévention des AVC et des TVC dans toutes les communautés (intégrées aux initiatives existantes de prévention des maladies chroniques) doivent être mises en place. 
2. Il faut améliorer la communication et la planification de la transition entre toutes les étapes et tous les établissements de soins et veiller à ce que les membres de l’équipe de soins primaires soient pleinement informés des objectifs des soins, des thérapies de prévention mises en place par les prestataires de soins de santé lors des premières évaluations (p. ex., dans les services des urgences), des rendez-vous de suivi pour les examens complémentaires et de la prise en charge à long terme. 
3. Les efforts doivent être coordonnés entre les parties prenantes comme Cœur + AVC, les organismes de santé publique, les ministères de la Santé et les prestataires de soins de santé dans l’ensemble du continuum de soins pour produire du matériel éducatif cohérent sur la prise en charge des facteurs de risque destiné aux patients, aux familles et aux aidants. 
4. Il faut coordonner les processus visant à assurer l’accès des professionnels de la santé, des patients et des aidants aux documents, programmes, activités et moyens de communication à contenu éducatif qui traitent de la prise en charge des facteurs de risque, y compris par des mesures efficaces de promotion et de diffusion.

Indicateurs du système : 

1. Fréquence annuelle de la TVC dans chaque province et territoire. 
2. Nombre de personnes présentant une TVC admises à l’hôpital chaque année.

Indicateurs de processus : 

3. Nombre de personnes réadmises à l’hôpital dans les 30 jours, dans les 90 jours et durant l’année suivant l’admission initiale relative à la TVC, classé par motif de réadmission. 
4. Nombre de consultations dans des unités de soins de courte durée après la sortie de l’hôpital par des personnes présentant une TVC.
5. Nombre d’examens de suivi effectués chez des personnes présentant une TVC, classé en fonction de l’âge et du sexe (surtout dans les cas de thromboses cérébrales et de TVC répétées chez les jeunes personnes) dans l’année suivant le diagnostic. 
6. Proportion de personnes présentant une TVC que l’on oriente vers des services d’évaluation aux fins de la réadaptation, au moment du congé de l’hôpital ou après un an. 
7. Proportion de personnes présentant une TVC que l’on oriente vers des surspécialistes, classée par spécialité (p. ex., ophtalmologie ou hématologie), à l’hôpital et 30 jours après le congé. 

Indicateurs de résultats et d’expérience axés sur le patient : 

8. Taux de mortalité associée à la TVC dans les provinces et territoires, y compris le taux de mortalité à l’hôpital, dans les 30 jours suivant l’événement et durant l’année suivant l’événement (indicateurs de qualité clés). 
9. Évaluation de la qualité de vie 30 jours et 90 jours après la TVC, à l’aide d’un outil validé.
10. Proportion de personnes présentant une TVC incapables de retourner au travail ou aux études après l’événement de référence.
11. Proportion de personnes présentant une TVC qui ont des effets indésirables ayant des répercussions sur leur vie quotidienne (p. ex., changements d’humeur, fatigue, troubles cognitifs, céphalées persistantes) 30 et 90 jours après le diagnostic. 

Notes relatives à la mesure des indicateurs

1. Il convient d’utiliser des outils validés pour mesurer la qualité de vie, l’humeur, les changements cognitifs et d’autres effets.
2. Indicateur n° 5 : En raison de la fréquence plus faible de la TVC par rapport à d’autres types d’AVC, les numérateurs et les dénominateurs peuvent devenir très petits lorsque l’on examine plusieurs sous-catégories de complications et que l’on classe les cas par âge et par sexe. Des variables de regroupement plus importantes peuvent être nécessaires.

Les ressources et les outils ci-dessous qui sont externes à Cœur + AVC et aux Recommandations peuvent être utiles à la mise en œuvre des soins de l’AVC. Cependant, leur présence ne constitue pas une approbation réelle ou implicite par l’équipe des pratiques optimales de soins de l’AVC ni par Cœur + AVC. Nous vous encourageons à examiner ces ressources et ces outils d’un œil critique et à les mettre en œuvre dans votre pratique à votre discrétion.

Renseignements destinés aux prestataires de soins de santé

• Module sur la thrombose veineuse cérébrale des Recommandations canadiennes pour les pratiques optimales de soins de l’AVC : annexe quatre « Schéma de cheminement relatif au dépistage du syndrome des antiphospholipides »
• Cœur + AVC, « Signes de l’AVC »
• CVT Consortium
• Cœur + AVC, « VITE… et les autres signes de l’AVC »
• Cœur + AVC, « Liste de vérification après un AVC » 
• Cœur + AVC, « Trousse d’outils pour la mise en œuvre des soins virtuels de l’AVC »
• Cœur + AVC, « Agir pour des soins de l’AVC optimaux communautaires et de longue durée (ASACL) : Une ressource pour les dispensateurs de soins de santé » 
• Info AVC

Renseignements destinés aux personnes ayant subi un AVC, y compris les membres de la famille, les proches et les aidants

• Cœur + AVC, Infographie sur la thrombose veineuse cérébrale
• Cœur + AVC, « Signes de l’AVC »
• CVT Consortium
• Cœur + AVC, « VITE… et les autres signes de l’AVC »
• Cœur + AVC, « Votre cheminement après un AVC »
• Cœur + AVC, « Liste de vérification après un AVC » 
• Cœur + AVC, « Aide à l’autogestion après un AVC : liste de vérification pour les patients, les familles et les aidants 
• Cœur + AVC, « Guide familial de l’AVC pédiatrique »
• Cœur + AVC, « L’AVC chez les jeunes adultes : une ressource pour les patients et les familles » 
• Cœur + AVC, Infographie sur la prévention secondaire 
• Cœur + AVC, Infographie sur la réadaptation et le rétablissement 
• Cœur + AVC, Infographie sur les transitions et la participation communautaire 
• Cœur + AVC, « Aide-mémoire pour les soins de santé virtuels » 
• Cœur + AVC, « La magie de la communauté » (soutien en ligne par les pairs) 
• Info AVC

Tableau des données probantes et liste de références

Factors related to clinical decision-making for anticoagulation

Please see Section 2.1, “Antithrombotic management,” for discussion of the evidence related to timing of transition from parenteral to oral anticoagulation. 

Vitamin K antagonists have been the longstanding guideline-recommended treatment for secondary prevention after CVT (Ferro et al. 2017). Recently, multiple observational studies and small randomized trials have compared efficacy and safety of DOACs against warfarin for CVT. The RE-SPECT CVT trial randomized 120 individuals with CVT 1:1 to six months with dabigatran 150 mg bid, versus warfarin, target INR 2.0 - 3.0 (Ferro et al. 2019). There were no VTE recurrences in either group at 6 months. There were two major GI hemorrhages in the dabigatran group and one symptomatic intracranial hemorrhage in the warfarin group. There were no differences between groups with respect to recanalization. The pediatric EINSTEIN-Jr trial randomized 114 children with CVT 2:1 to three months of 20 mg equivalent dosing of rivaroxaban versus standard-of-care anticoagulation with either VKA, target INR 2.0 - 3.0, or low molecular-weight heparin (Connor et al. 2020). There was one recurrent VTE in the comparator group. Rates of recanalization were similar between groups. There were 5 clinically relevant non-major bleeding events in the rivaroxaban group and one symptomatic intracranial hemorrhage in the comparator group. The SECRET feasibility trial randomized 50 individuals with CVT 1:1 to a minimum of six months with rivaroxaban 20 mg daily versus standard-of-care anticoagulation with either warfarin, target INR 2.0 - 3.0, or low molecular-weight heparin (Field et al. 2023). At six months, there was one recurrent VTE in the rivaroxaban group. There was one symptomatic intracranial hemorrhage and two clinically relevant non-major bleeding events in the rivaroxaban group. There were no VTE recurrences, major or clinically relevant non-major bleeding events in the comparator group. There were no differences between groups with respect to recanalization. ACTION-CVT was a large retrospective international study comparing safety and efficacy of DOACs versus VKA prescribed to individuals with CVT as part of their routine clinical care (Yaghi et al. 2022b). Apixaban was the most commonly prescribed DOAC (67%), followed by rivaroxaban (18%) and dabigatran (14%), or other or multiple DOACs (3%). Rates of recurrent VTE did not differ between groups (aHR 0.94, 95% CI 0.15 - 1.73). There was a lower risk of major hemorrhage in the DOAC group (aHR 0.35, 95% CI 0.15 - 0.82), primarily driven by a lower risk of ICH. There were no differences in rates of partial or complete recanalization at a median of 345 days (IQR 140-720). A recent systematic review including three randomized trials and 16 observational studies comparing DOACs to VKAs found similar risks between groups with respect to VTE recurrence, major hemorrhage and complete recanalization (Yaghi et al. 2022a). Overall, the literature support using DOACs as an alternative to VKA in lower-risk individuals with CVT. DOACs are now included as an option for anticoagulation in CVT in the updated AHA/ASA guidelines (Saposnik et al. 2024).

Certain groups are excluded, or underrepresented, in studies to date comparing DOACs to warfarin. DOACs are contraindicated in pregnancy and breastfeeding and thus this population has been excluded by design. In addition to those who were pregnant, both RE-SPECT CVT and ACTION-CVT excluded individuals with malignancy, central nervous system infection, trauma and pregnancy. ACTION-CVT and SECRET excluded individuals with known antiphospholipid antibody syndrome. While malignancy-, infection- or trauma-associated CVT were not exclusion criteria for SECRET, these groups are not well-represented in the study. EINSTEIN-Jr had a large proportion of participants with CVT associated with head and neck infection (65%); less so major head trauma (7%) or active cancer (8%). No specific concerns related to use of DOACs were identified in these groups. The role of DOACs in malignancy-associated CVT remains an area of controversy, although randomized trials from the general (i.e. non-CVT) VTE literature suggest that DOAC is an acceptably safe and efficacious alternative to LMWH in malignancy-associated VTE (Agnelli et al. 2020; McBane et al. 2020; Raskob et al. 2018; Schrag et al. 2023; Young et al. 2018).

Clinical trials comparing DOACs to warfarin for prevention of venous and arterial events in antiphospholipid antibody syndrome (APLAS) have demonstrated an excess of thromboembolic events with DOAC. The TRAPS trial, which compared rivaroxaban to warfarin in 120 individuals with high-risk APLAS (triple-positive with a history of previous arterial or venous thromboembolism) was stopped early due to an excess or arterial events in the rivaroxaban arm without any events in the warfarin arm (Pengo et al. 2018). A Spanish trial also examining rivaroxaban versus warfarin in 190 individuals with thrombotic APLAS found an excess of arterial thromboembolic events with rivaroxaban that was nearly double that of the warfarin group (Ordi-Ros et al. 2019). The ASTRO-APS trial, which was limited due to protocol modifications and slow recruitment, compared apixaban (initially 2.5 mg bid later changed to 5 mg bid) against dose-adjusted warfarin in 48 patients with definite (42%), likely (25%) or historical (33%) APLAS (Woller et al. 2022). There was a high rate of arterial thromboembolic events in the apixaban group compared to none in the warfarin group and the study was terminated having recruited one-quarter of its target sample size. 

Duration of anticoagulation

In those without a permanent indication for anticoagulation following CVT, including antiphospholipid antibody syndrome, active malignancy, or major-risk hereditary thrombophilia, the optimal duration of anticoagulation for CVT is not known. 

Previous AHA/ASA and European guidelines for the management of CVT recommend the initial use of parental heparin followed by transition to oral vitamin K antagonists (VKA) for 3-12 months in the context of transient risk factors, or indefinitely in the context of chronic major risk factors for thrombosis or recurrent VTE (Einhäupl et al. 2010; Ferro et al. 2017). Previous surveys of physician practices, and the recent Canadian SECRET randomized trial, suggest that most patients without an indication for permanent therapy are currently treated for 6-12 months (Coutinho et al. 2011b; Field et al. 2017).

This approach, however, diverges somewhat from current recommendations around management of DVT/PE from the general VTE literature. For DVT/PE, the first 3-6 months following VTE are considered as the “primary treatment” phase, with subsequent ongoing therapy termed “secondary prevention.” In the general VTE literature, events that are provoked in the context of a transient risk factor receive 3-6 months of primary treatment without secondary prevention. Events provoked by a chronic risk factor, however, may be indefinitely anticoagulated given the net clinical benefit of long-term versus short-term anticoagulation in this population, with decision-making based on a follow-up period of approximately 2 years. Overall, risk of bleeding is increased approximately two-fold, while relative rates of VTE recurrence and mortality are reduced by 20-30% and 75%, respectively.

How these results should be extrapolated to the CVT population, however, is unclear. The CVT population includes a high proportion of younger women with transient sex-specific provoking risk factors, including oral contraceptives and the puerperium. Outside of high-risk thrombophilias and those with a history of recurrent events, overall risks of recurrent CVT and other VTE appear to be low (Shu et al. 2022). However, certain groups, including those with unprovoked events, men, and heterozygotes for genetic thrombophilias such as Factor V Leiden and prothrombin gene mutation, (Palazzo et al. 2017; Pires et al. 2019) may have a higher risk. Estimated risks of recurrence are somewhat variable. A review of 4 observational studies from the American Society of Hematology estimated an overall rate of VTE recurrence of 38/1000 over the first year (Dentali et al. 2012a; Martinelli et al. 2010; Miranda et al. 2010; Palazzo et al. 2017). The recent retrospective ACTION-CVT study found a recurrence of 51 recurrent VTE (de novo recurrent CVT and peripheral VTE) per 1000 patient-years (Shu et al. 2022). There are additional inconsistencies in the literature around whether risk of recurrence is heightened in the first year as compared to subsequent years, (Shu et al. 2022) versus a more linear increase over subsequent years (Palazzo et al. 2017).

Additional information regarding duration of shorter versus longer durations of primary anticoagulation will be brought forth by the ongoing EXCOA trial comparing 3-6 months versus 12 months of anticoagulation (Miranda et al. 2018).

Refer to Section 3.2, “Role of Routine Follow-up Vascular Neuroimaging” around the role of repeat neuroimaging as it relates to duration of anticoagulation. 

CVT workup: cancer screening

There is no strong evidence to date to suggest that individuals with CVT should receive enhanced cancer screening. A recent Danish population-based study with a median follow-up of 6.2 years found that overall, rate of incident cancer was not significantly higher in individuals with a diagnosis of CVT. Of 811 patients with CVT, 43 had an incident cancer diagnosis over time, rates that were similar to another recent Swedish population-based study (Sipilä et al. 2022). Risks of incident cancer compared to the general population were elevated over the first year following diagnosis, however, these high rates were driven by a small number of cases overall. The authors estimated that the number of patients to be screened in the six months after CVT to detect one additional incident cancer was 85.5 (95% CI 55.3 - 188.2) overall, 122.1 (95% CI, 71.7 - 411.2) in patients aged 18-54 years and 47.5 (26.2 - 258.8) in those aged >55 years (Skajaa et al. 2023). These numbers needed to screen are similar to those of DVT/PE.

Testing for Janus Kinase V617F mutations in people with CVT without signs or symptoms of myeloproliferative neoplasm (MPN) remains an area of controversy (Xavier et al. 2011). Larger cohorts of mostly unselected CVT patients from Italy, India and Israel report rates of 5.6-6.5% of the JAK2 V617F mutation (De et al. 2012; Lamy et al. 2017; Passamonti et al. 2012; Simaan et al. 2023). All series note that many diagnosed with the mutation at the time of their CVT did not meet criteria for MPN diagnosis.

CVT workup: hypercoagulability testing

Practices and recommendations around hypercoagulability testing following VTE continue to evolve. The recent guidelines from the American Society of Hematology for thrombophilia testing for management of venous thromboembolism included a conditional recommendation for patients with CVT where anticoagulation would otherwise be discontinued (Middeldorp et al. 2023). This recommendation was based on an estimate that, based on an annual recurrent risk of 38/1000/year (Dentali et al. 2012a; Martinelli et al. 2010; Miranda et al. 2010; Palazzo et al. 2017), that a strategy of testing for thrombophilia followed by indefinite anticoagulation in patients with thrombophilia, and stopping anticoagulation in patients without thrombophilia, would result in 18 (range 14-23)/1000 fewer recurrent VTE compared to a no-testing strategy.

Recommendations related to hypercoagulability testing for specific conditions have been published previously by the International Society on Thrombosis and Haemostasis and the International Society for Laboratory Hematology (Baker et al. 2020; Barbhaiya et al. 2023; Devreese et al. 2014; Marlar et al. 2021; Tripodi et al. 2020).

CVT workup: antiphospholipid antibody testing

Please see Section 3.1, Factors related to clinical decision-making for anticoagulation, for a summary of the evidence related to warfarin versus DOACs in people who have a diagnosis of APLAS. 

Given that a diagnosis of APLAS would affect decisions around choice of antithrombotic, it is reasonable to test for antiphospholipid antibodies in patients with CVT who do not have a previous diagnosis. In the absence of a history of APLAS or clinical suspicion of APLAS, however, it is reasonable to proceed with anticoagulation as if the patient did not have APLAS, without waiting for test results, and then altering the anticoagulant accordingly if testing is positive. The prevalence of APLAS-associated CVT is not known. A systematic review cited rates of 6-17% of positive antiphospholipid antibody testing in previous series, (Silvis et al. 2016) although definitions varied between studies and up to 5% of healthy individuals are noted to have antiphospholipid antibodies (Dabit et al. 2022).

Role of routine follow-up vascular neuroimaging

The literature comparing diagnostic accuracy of contrast-enhanced CT venography and contrast-enhanced MR venography to non-enhanced neuroimaging mainly relates to diagnosis of CVT, and not recanalization on follow-up imaging. One small study comparing contrast-enhanced versus time-of-flight MR venography in 6 patients with CVT undergoing follow-up imaging found that 10/15 venous segments on contrast-enhanced MRV with peripheral enhancement and a central non-enhancing filling defect showed peripheral continuous channel morphology on time-of-flight MR venography. However, the study was cross-sectional and did not compare modalities with respect to assessing recanalization from baseline scans (Leach et al. 2007).

Whether degree of venous recanalization should inform duration of anticoagulation remains an area of uncertainty (Aguiar de Sousa et al. 2020; Aguiar de Sousa et al. 2018b; Ferro et al. 2022; Kim et al. 2023). Although a subset of clinicians will modify their duration of anticoagulation based on the degree of venous recanalization on repeat neuroimaging, (Field et al. 2017) it is unclear if this strategy is beneficial. An early prospective neuroimaging study found that 68% of patients experienced partial, and 4%, full recanalization, after one week of anticoagulation. By day 90, 95% of patients had partial (41%) or complete (54%) recanalization (Aguiar de Sousa et al. 2020). A substudy of the ACTION-CVT study found that 88.2% of patients had partial (48.5%) or complete (39.7%) recanalization. Of those patients who had complete recanalization, 59% were noted to be fully recanalized by three months, with 15.4% of additional patients achieving complete recanalization by 6 months and 16.7% by 12 months (Salehi Omran et al. 2023).

A recent prospective neuroimaging study noted that anticoagulated patients with a diagnosis of CVT who had at least partial recanalization within the first 8 days of treatment had fewer new non-hemorrhagic lesions and less extension of pre-existing non-hemorrhagic lesions. However, this was not associated with a reduction in headache or improved functional outcomes at day 90 (Aguiar de Sousa et al. 2020). Most recanalization literature focuses on later recanalization, past the three-month mark. A recent meta-analysis of observational data found that complete or partial venous recanalization was associated with an improved odds of a favourable functional outcome as compared with no recanalization as well as lower risk of recurrence and less presence of common headache (Aguiar de Sousa et al. 2018b). However, there was significant heterogeneity between studies, and the directionality of the association between recanalization and outcomes remains uncertain. The authors note that in meta-regression, the relationship between recanalization and functional outcomes was modified by sex. A prospective substudy of RESPECT-CVT found no association between recanalization and functional outcome (Ferro et al. 2022). Whether recanalization status is causally related to other post-CVT sequelae, including visual loss, cognition or development of dural arteriovenous fistulae (dAVF), is not known.    

At present, there is no strong evidence to suggest routine follow-up neuroimaging to screen for dAVF after CVT. A substudy of the RE-SPECT CVT study found that out of 112 patients, none developed dAVF at six months on repeat MR venography (Ferro et al. 2020). A retrospective study from the international CVT consortium found that out of 1218 patients, 2.4% were found to develop dAVF on neuroimaging performed at a median of 6 months (IQR 5-12). Risk factors for dAVF included male sex, older age and late presentation with CVT (>30 days following symptom onset) (Lindgren et al. 2022).

Management of other post-acute sequelae of CVT

Although rates of functional independence after CVT are high, survivors are noted to have reduced quality of life, with a high prevalence of residual symptoms related to headache, depression, fatigue and cognitive impairment. In the Canadian SECRET trial, 72% of participants were functionally independent (modified Rankin 0 - 2) at the time of their diagnosis. However, mean baseline assessments were indicative of mild-moderate depression, substantial-severe impact of headache, substantial fatigue and impaired cognitive performance. On average, participants experienced improvements in all patient-centered metrics over time between baseline and day 180 and at day 365. Other retrospective studies suggest that reduced participation may persist in many survivors. A retrospective study from China including CVT patients who were employed or in school prior to their index event found that 42% had not returned at six months. Aphasia, cognitive impairment and recurrent CVT were independent predictors for an inability to return to previous activities (Liu et al. 2023).

The definition of “late seizures” in the CVT literature generally refers to those experiencing an event at seven days following presentation or later. A combined prospective and retrospective study from the International Cerebral Venous Thrombosis Consortium found that 11% of 1127 patients were noted to have late seizures, median time to onset being 5 months (IQR 1 - 16 months) (Sánchez van Kammen et al. 2020). ASM was prescribed in 45% of patients prior to the first late seizure and in 94% following the first late seizure. Of those with late seizures, 70% were noted to have later recurrence, with a median time to recurrence of 1 month (IQR 0 - 8). However, the authors did not specify what proportion of those with later recurrence were no longer taking ASM. Independent risk factors for late seizures included acute seizures or status epilepticus at presentation, intracranial hemorrhage, subdural hematoma specifically, and decompressive hemicraniectomy. A meta-analysis including the aforementioned study and three smaller studies identified similar risk factors for late seizures (Gasparini et al. 2022). 

Sex, gender and other equity-related considerations

Considerations related to choice of anticoagulant in women who are pregnant or breastfeeding are summarized in Section 4.1, CVT and pregnancy. Warfarin is a known teratogen and individuals with the potential to become pregnant should be counselled to use effective contraception while on this medication. 

Determining duration of primary anticoagulation or strategies around secondary prevention anticoagulation may involve shared decision-making between patients and clinicians. Clinicians are encouraged to consider the potential for heavy menstrual bleeding in discussions with patients who menstruate and to take a thorough menstrual history as well as a complete blood count and ferritin at baseline. Refer to section 4.1, clinical considerations, anticoagulation and heavy menstrual bleeding for further summary of the existing evidence around assessment and management of heavy menstrual bleeding.

In a substudy of the ACTION-CVT study, Black race was an independent risk factor for recurrent VTE (HR 2.13, 95% CI 1.14-3.98), both overall in a sensitivity analysis examining events occurring off oral anticoagulation (HR 2.59, 95% CI 1.17-5.75). Provoking factors were not significantly different between individuals with Black race versus non-Black race, with lower rates of Factor V Leiden and prothrombin gene mutations in individuals with Black race. Black race was associated with lower rates of follow-up with INR checks in warfarin-treated patients. The authors concluded that, similar to what has been reported in the overall stroke literature, (Towfighi et al. 2023) that the increased risk associated with Black race was likely due to social determinants of health, including disparities in access to care, structural racism and socioeconomic inequities (Shu et al. 2022).