What are the management and treatment guidelines for Cerebral Venous Sinus Thrombosis (CVST)?

Management of Cerebral Venous Sinus Thrombosis (CVST)

For patients with CVST, immediate anticoagulation with either low-molecular-weight heparin (LMWH) or unfractionated heparin (UFH) is strongly recommended as first-line treatment, even in the presence of hemorrhagic lesions. 1, 2, 3

Initial Anticoagulation Therapy

LMWH Regimen

• Enoxaparin (Clexane) 1.0 mg/kg twice daily or 1.5 mg/kg once daily is the preferred initial treatment option due to superior efficacy compared to UFH 2, 4
• LMWH has been associated with significantly lower hospital mortality compared to UFH in CVST patients 4

UFH Alternative Regimen

• UFH should be used if there is renal failure, need for rapid reversal, or high bleeding risk 2
• Initial bolus of 5000 IU, followed by continuous infusion of approximately 30,000 IU over 24 hours 2
• APTT target is 1.5-2.5 times upper limit of normal (ULN) 2, 5

Transition to Oral Anticoagulation

Oral Anticoagulant Options

• Three oral anticoagulants that can be overlapped with heparin include:
  1. Warfarin (vitamin K antagonist)
  2. Direct oral anticoagulants (DOACs): apixaban, rivaroxaban, dabigatran 2, 6
• When using warfarin, INR target is 2.0-3.0 (target 2.5) times ULN 2, 7

DOAC Dosing

• Dabigatran: 150 mg twice daily (110 mg twice daily for patients >80 years or at high bleeding risk) 2, 6
• Rivaroxaban: 15-20 mg once daily with food 2, 6
• Apixaban: 5 mg twice daily (2.5 mg twice daily for patients meeting two of: age ≥80 years, weight ≤60 kg, or serum creatinine ≥1.5 mg/dL) 2, 6
• Edoxaban: 60 mg once daily (30 mg once daily for patients with CrCl 15-50 mL/min, weight ≤60 kg, or on certain P-gp inhibitors) 2, 6

Duration of Anticoagulation

Provoked CVST

• Duration of anticoagulation for provoked CVST is 3-6 months 1, 3, 7
• Provoked refers to CVST associated with transient risk factors (e.g., pregnancy, infection, dehydration) 7

Unprovoked CVST

• Duration of anticoagulation for unprovoked CVST is 6-12 months 3, 7
• Consider indefinite anticoagulation for recurrent events or severe thrombophilia 7

Conditions Requiring Lifelong Anticoagulation

1. Recurrent CVST (two or more episodes) 5, 7
2. CVST with severe hereditary thrombophilia 5, 7
3. CVST associated with antiphospholipid syndrome 1, 7
4. CVST associated with active cancer 2, 3

Special Considerations

Pregnancy

• LMWH is the anticoagulant of choice during pregnancy 2, 5
• Warfarin is contraindicated during pregnancy due to risk of fetal warfarin syndrome 5

Fetal Warfarin Syndrome

• Also called warfarin embryopathy 5
• Characterized by nasal hypoplasia, stippled epiphyses, and limb abnormalities 5

Conditions Where Warfarin is Preferred Over DOACs

1. Mechanical heart valves 1, 2
2. Antiphospholipid syndrome 1, 2
3. Severe renal impairment (CrCl <15-30 mL/min depending on the DOAC) 1, 2

Management of Increased Intracranial Pressure

Mannitol Administration

• Mannitol bolus dose is 0.5-1.0 g/kg 5
• 100 mL Mannitol bottle (20% solution) contains 20 g 5

Follow-up Care

• Follow-up imaging at 3-6 months after diagnosis is recommended to assess recanalization 3
• Regular neurological assessment is necessary to detect clinical deterioration 2
• Investigate underlying prothrombotic conditions as this affects treatment duration 3, 7

Evidence Quality and Considerations

• LMWH has demonstrated superior outcomes compared to UFH in CVST treatment, with one study showing zero mortality in the LMWH group versus six deaths in the UFH group 4
• The presence of intracranial hemorrhage related to CVST is NOT a contraindication for anticoagulation 1, 2, 3
• Recent evidence suggests NOACs may be as effective and safe as warfarin for CVST treatment, with potentially improved clinical outcomes 6