Towards A Better Understanding Of Cerebral Venous Thrombosis

Cerebral venous thrombosis (CVT) is a rare cause of stroke, predominantly affecting young reproductive-age women with a 6-15% death or dependency rate. In this thesis, I evaluated a large sample of adult CVT to determine the impact of age, gender, and risk factors on the onset, severity, and long-term outcome of CVT. I began by conducting a meta-analysis to compare the safety and effectiveness of direct oral anticoagulants (DOACs) and warfarin for the long-term (≥6 months) treatment of CVT. The literature on adult CVT was reviewed, noting that most studies were outdated and featured small sample sizes.
I integrated data from the prospective observational BEAST study (Biorepository to Establish the Aetiology of Sinovenous Thrombosis). The study recruited 1309 CVT patients (aged ≥18 years) of European ancestry from 11 countries in the UK, Europe, the USA, and Mexico.
I discovered that women suffered CVT 9 years earlier than men, and women with ≥1 risk factor suffer CVT ~12 years earlier than those with no identifiable risk factors. Further, the likelihood of CVT is ~4 times higher at ≥45 years in those with malignancy (Odds Ratio [OR]: 3.6, 95% CI 1.4-9.0; P=0.006).
A genetic analysis was undertaken on this cohort. This is the first study to identify PROC (protein C) SNPs (rs1799810, rs41280570, rs1158867, rs2069919, and rs5937) as potential genetic determinants linked to an increased risk (OR ~1.3) of CVT in Europeans. Moreover, the higher F8 level is an X-linked inherited disorder that increases the risk of superior sagittal sinus thrombosis by ~8 times in men, but only ~2 times in women.
Although CVT is a women-dominant disease, I observed that men are ~2-fold more likely to suffer from coma compared to women. Additionally, I found cerebral haemorrhage and endovascular thrombolysis were strong independent predictors of the long-term poor clinical outcome in CVT.
Finally, a meta-analysis evaluated 25 studies involving 2301 patients comparing outcomes between DOACs and warfarin in CVT management. I found comparable long-term outcomes represented by good clinical outcomes, new intracranial haemorrhage, all-cause mortality, non-recanalisation, and recurrence venous thrombosis events between the DOACs and warfarin arms.
Based on the current thesis findings, early diagnosis and effective management strategies are essential for enhancing the prognosis in adult CVT. Further, while DOACs and warfarin have similar long-term outcomes, DOACs are often preferred over warfarin due to their easier clinical management.