Cerebral venous thrombosis and pregnancy

• cerebral venous thrombosis (CVT) is a rare but life-threatening disease in pregnant women
• pregnancy induces changes in the coagulation system that persist into the puerperium and result in a hypercoagulable
  state, increasing the risk of CVT
• the risk is highest in the third trimester and the first 6 postpartum weeks (5-20% of the cases)
  • approximately 80% of pregnancy-related CVT cases occur after delivery
  • cesarean delivery appears to be associated with a higher risk
• other important risk factors include genetic thrombophilia, systemic diseases, infections, and cancer

• symptoms are the same as in nonpregnant individuals and may include headache, vision changes, seizures, weakness, nausea, and vomiting

• diagnosis is preferably made by using magnetic resonance imaging (MRI)/MR-venography due to the non-ionizing and non-invasive character
  • Time Of Flight (TOF) MR venography should be used
  • the use of contrast should be limited and only used when the benefits outweigh the possible risks for the fetus
• CT+CT venography if MRI/MRV is contraindicated or unavailable (careful fetal shielding with a lead apron is required!)
  • CT venography is assumed to be as accurate as MR venography
  • CT has reduced sensitivity for detecting cortical vein thrombosis and early parenchymal lesions compared to MRI

→ Neuroimaging in pregnancy

• if CVT is suspected during pregnancy or puerperium, one can consider cerebral imaging instead of measuring D-dimers
• D-dimers are unspecific and tend to be increased due to the increased fibrinolysis following fibrin formation throughout pregnancy

• standard treatment of CVT in pregnant and puerperal patients is anticoagulation
  • subcutaneous LMWH is preferred throughout pregnancy due to its safety profile
    • LMWH does not cross the placenta and has a good safety profile; studies have reported better outcomes with no significant risk of maternal or fetal hemorrhagic complications
      
  • UFH has the advantage of a short half-life with dose adjustments based on APTT and can be antagonized using protamine sulfate
    • although UFH is considered safe in pregnancy, associations with increased risk of fetal hemorrhage and teratogenicity have been described
  • vitamin K antagonists are contraindicated during pregnancy
  • DOACs, such as factor Xa inhibitors (apixaban, edoxaban, rivaroxaban) or thrombin inhibitors (dabigatran), are also contraindicated because they are likely to cross the placenta and teratogenic risks are not known
• in severe cases or when anticoagulation therapy fails, endovascular treatment or surgery (life-saving decompressive craniectomy) may be effective (Zhou, 2022)
  • only case reports of endovascular treatment and decompressive craniectomy in pregnant women with CVT have been published
• other treatments are symptomatic, addressing issues such as seizures, etc.

• the optimal dose of LMWH for thromboprophylaxis in pregnant women at moderate to high risk of venous thromboembolism recurrence is unknown
• prophylactic or intermediate doses of LMWH are currently two options, of which the prophylactic dose is the most often prescribed in the clinical setting
  • intermediate doses: enoxaparin 0.5 mg-1 mg/kg administered subcutaneously once or twice daily
  • prophylactic dose: enoxaparin 0,4 ml (40 mg) SC once daily
  • dose reduction is required in renal insufficiency
• therapeutic doses of LMWH are not widely accepted because of the possible bleeding risk during delivery

• as for nonpregnant women, a treatment period of 3–12 months can be advised (based on individual risk factors)
• therapeutic LMWH is typically continued for at least 6 weeks postpartum based on the known increased risk of CVT following delivery

• consider the mother’s wish regarding breastfeeding in the case of a lifelong indication for anticoagulation after the puerperium period
• LMWH is the gold standard during breastfeeding because it does not transfer easily into breastmilk
• UFH and warfarin are also acceptable during lactation
• DOACs should be avoided as no clinical data is available about their safety during lactation

• women with a history of VTE appear to have an increased risk of venous thromboembolism in future pregnancies
• reviews suggest a lower rate of recurrent thrombotic events in women who used antithrombotic prophylaxis (Sousa, 2018)
• therefore, thromboprophylaxis with LMWH throughout pregnancy and the postpartum period is probably beneficial (AHA guidelines 2023)
  • prophylactic LMWH seems appropriate (unless contraindicated or full anticoagulation is indicated) (ESO guidelines 2017) 
  • in the US, LMWH is administered from the 3rd trimester to the 8th week postpartum
  • data are weak and mostly from observational studies
• thromboprophylaxis with LMWH is considered safe and effective in preventing recurrent venous thromboembolism, though it may be associated with an increased risk of late obstetrical complications

• according to the available evidence, CVT is not a contraindication for future pregnancies
• prevention strategies include staying hydrated, maintaining physical activity as advised, and regular medical check-ups
• prophylactic dose of LMWH in women with a history of VTE may be considered (consult a hematologist)

• women with a history of CVT are advised against using estrogen-containing contraception due to the increased risk of recurrent CVT or other venous thromboembolic events
• instead, an intrauterine contraceptive device (IUD) is recommended
• progestogen-only contraceptives may be an alternative, but data on their safety is limited