Male Sex, Factor V Leiden Mutation Increase Recurrent VTE Risk After First Cerebral Venous Thrombosis

A new study found that male sex and factor V Leiden mutation were associated with a higher risk of recurrent venous thromboembolism (VTE) after a first cerebral venous thrombosis (CVT) event. Despite this higher risk, the authors reported, the overall recurrence rate of VTE after a first CVT event was relatively low.

“CVT is a rare vascular disease of the brain … characterized by the occlusion of venous sinuses and/or cerebral veins by thrombi,” the researchers, led by Giselli S. Pires, MD, from the Federal University of Minas Gerais in Brazil, wrote. Although CVT is known to occur more frequently in women and investigators have identified several risk factors for a first event, “few studies have assessed factors associated with the risk of VTE recurrence.”

In this multicenter cohort study, researchers followed 203 adult patients (median age = 30.8 years; interquartile range [IQR] = 24.7-40.9 years) who were diagnosed with a first symptomatic CVT event. Participants were monitored for a median of three years (IQR=1.2-5.6 years), with follow-up starting after the patients discontinued anticoagulant therapy and ending at either VTE recurrence, last appointment, or last contact.

At admission and subsequent follow-up visits, a standardized questionnaire was administered to collect patient information, data on first CVT (i.e., date of diagnosis, factor V Leiden mutation, prothrombin G20210A mutation, oral anticoagulant, and start and end dates of anticoagulation), and data on VTE recurrence (i.e., date of the event, age at the time of event, affected site, date of event confirmation by objective methods, and VTE recurrence risk factors).

Although certain factors increased the risk of recurrent VTE, the overall recurrence rate of VTE after a first CVT event was relatively low.

Most patients (86.2%) were women. Of those of reproductive age, approximately 65.4% (n=106/162) experienced CVT during oral contraceptive use, and another 8% developed CVT during pregnancy or in the six weeks following pregnancy. The CVT event was considered unprovoked in 54 patients (26.6%).

During study follow-up, 13 patients developed recurrent VTE, for a low overall rate of 1.6 per 100 patient-years. Recurrent VTE events included:

  • CVT (1.1%)
  • pulmonary embolism (PE; 1.6%)
  • lower-limb deep vein thrombosis (DVT; 4.2%)

Recurrence rates for the specific types of VTEs were:

  • CVT: 0.2 cases per 100 patient-years
  • Other types of VTE: 1.4 cases per 100 patient-years
  • PE: 0.4 cases per 100 patient-years
  • Lower-limb DVT: 1.0 cases per 100 patient-years

Approximately 23% of these patients developed a recurrent event during the first year following the initial CVT.

Recurrence rates did not appear to differ according to provoked or unprovoked status of the initial CVT; however, the recurrence rate was highest for patients with heterozygous factor V Leiden mutation (9.2 cases per 100 patient-years).

In the multivariate analysis, the researchers found that the following factors were associated with a significantly higher risk of recurrent VTE (p values not reported):

  • male sex (hazard ratio [HR] = 4.2; 95% CI 1.2–14.1)
  • presence of heterozygous factor V Leiden mutation (HR=6.8; 95% CI 1.3–34.2)

Although the findings from this analysis confirm that recurrent VTE is low after an initial CVT, the authors noted several potential limitations, including the study’s small sample size, the lack of confirmation of the objective CVT diagnostic methods used by the coordinating center, and the 14 patients who were lost to follow-up.

The authors report no conflicts of interest.


Pires GS, Ribeiro DD, Oliveira JAQ, et al. Risk factors associated with recurrent venous thromboembolism after a first cerebral venous thrombosis event: A cohort study. Thromb Res. 2019;178:85-90.