What are the causes of cerebral venous sinus thrombosis (CVST) in young female patients?

Causes of Cerebral Venous Sinus Thrombosis in Young Female Patients

Oral contraceptive use is the single most important modifiable risk factor for CVST in young women, with 85-96% of young female CVST patients using oral contraceptives, conferring a 13-22 fold increased risk. 1

Primary Risk Factors in Young Women

Hormonal Factors (Most Common)

• Oral contraceptives represent the dominant acquired risk factor, with meta-analyses showing a relative risk of 15.9 (95% CI 6.98-36.2) and odds ratio of 5.59 (95% CI 3.95-7.91) 1
• The majority of younger nonpregnant women with CVST are oral contraceptive users 1
• Pregnancy and puerperium account for a substantial proportion of cases, with an estimated 12 cases per 100,000 deliveries 1
• Most pregnancy-related CVST occurs in the third trimester or postpartum period, with 7 of 8 pregnancy-related CVTs occurring postpartum 1
• Risk increases with cesarean delivery, maternal age, hypertension, infections, and excessive vomiting in pregnancy 1

Inherited Thrombophilias (Critical to Identify)

• Protein C deficiency carries a combined odds ratio of 11.1 for CVST 1, 2
• Protein S deficiency and antithrombin III deficiency are significant risk factors, though antithrombin III deficiency is rare (only 2% in one series) 1
• Factor V Leiden mutation and prothrombin G20210A mutation are important genetic thrombophilias 1, 2
• Hyperhomocysteinemia is another significant prothrombotic risk factor 2, 3

Synergistic Risk Amplification (Critical Clinical Pitfall)

The combination of oral contraceptives with inherited thrombophilia dramatically amplifies CVST risk beyond either factor alone:

• Factor V Leiden + oral contraceptives: OR 30.0 (95% CI 3.4-263.0) 1
• Prothrombin G20210A mutation + oral contraceptives: OR 79.3 (95% CI 10.0-629.4), with one study showing OR 149.3 1
• This multiplicative effect means young women on oral contraceptives with undiagnosed thrombophilia face exponentially higher risk 1

Secondary Causes to Consider

Malignancy

• Cancer accounts for 7.4% of CVST cases, particularly hematologic malignancies 1
• Mechanisms include direct tumor compression, sinus invasion, hypercoagulable state, and chemotherapeutic/hormonal agents 1

Infections

• Parameningeal infections (ear, sinus, mouth, face, neck) explain 8.2% of adult cases 1
• This is notably less common in adults than children (where 40% are infection-related) 1

Emerging Risk Factors

• Obesity and polycystic ovary syndrome are newly recognized risk factors 4
• COVID-19 infection and vaccine-induced thrombocytopenia and thrombosis 4

Rare Hematologic and Inflammatory Conditions

• Paroxysmal nocturnal hemoglobinuria, iron deficiency anemia, thrombocythemia 1
• Systemic lupus erythematosus, Behçet disease, inflammatory bowel disease 1
• Nephrotic syndrome, thrombotic thrombocytopenic purpura 1

Clinical Approach Algorithm

When evaluating a young woman with suspected CVST:

1. Immediately assess oral contraceptive use - present in the vast majority of cases 1
2. Determine pregnancy/postpartum status - particularly high-risk in puerperium 1
3. Screen for inherited thrombophilias - especially if on oral contraceptives, given synergistic risk 1
4. Evaluate for hyperhomocysteinemia - particularly in pregnant/postpartum women 1, 2
5. Consider malignancy screening if no obvious risk factors identified 1
6. Rule out parameningeal infections with appropriate imaging and examination 1

Key Clinical Caveat

In approximately 34% of CVST cases, an inherited or acquired prothrombotic condition is identified 1. However, the presence of oral contraceptive use is so dominant in young women that it should be the first line of investigation, with thrombophilia screening essential given the multiplicative risk when both factors coexist 1.