Management in the subacute phase of cerebral venous thrombosis

Created 08/04/2021, last revision 16/11/2023

Anticoagulant therapy

acute parenteral therapy (usually using LMWH) is replaced by oral anticoagulant therapy
WARFARIN with a target INR 2-3 → see here
DOACs seem to have similar efficacy and better safety profiles [Geisbüsch, 2014]
- positive results of the RE-SPECT CVT trial
  - n=120 (dabigatran 2x150mg vs. warfarin with INR 2-3), treatment duration 24 weeks
  - 5-15 days pretreatment with parenteral heparin, major bleeding 1 vs. 2 (warfarin), no thrombotic events
- the ACTION-CVT (2022) trial showed equal efficacy of DOACs and warfarin, with DOACs having a lower risk of major bleeding (HR 0.35)
- DOACs are not recommended in the acute phase (ESO guidelines 2017)

therapy of CVST provoked by VITT (Vaccine-induced Immune Thrombotic Thrombocytopenia)
- DOACs are preferred (American Society of Hematology guidelines for HIT therapy – 2018)
- switch to oral anticoagulation is advised only after normalization of platelet count

warfarin	LMWH	DOAC
antiphospholipid syndrome (APL) hypercoagulable states (Leiden, etc.)	pregnancy active cancer	active cancer VITT (Vaccine-induced Immune Thrombotic Thrombocytopenia) other causes of CSVT

the decision regarding the duration of anticoagulant therapy is based on individual hereditary and provoking factors, as well as the potential bleeding risks associated with long-term treatment (Einhäupl, 2006]
sinus recanalization most commonly occurs within the first 3-4 months; the rate of rethrombosis is low
regular follow-up visits should be conducted after discontinuing anticoagulant therapy
patients should be educated about early signs of potential relapse (most commonly headache)

3-6 months	transient risk factors (e.g., oral contraceptives, puerperium, infection)
6-12 months	idiopathic (unprovoked) thrombosis mild thrombophilia (e.g., heterozygous Leiden V or MTHFR), then switch to aspirin (AHA/ASA 2014 IIa/C) some clinicians use repeated venous imaging to guide the duration of therapy
long-term anticoagulation	recurrent venous thrombosis severe thrombophilia (e.g., Leiden homozygote, prothrombin G20210A mutation, protein C and S deficiency, antiphospholipid antibodies)

avoid estrogen-containing contraceptives (ESO guidelines 2017)
- an intrauterine contraceptive device (IUD) is advised
in the absence of a hypercoagulable state or a history of previous thromboembolism, recurrent venous thrombotic events during subsequent pregnancy are rare [Sousa, 2017]
- educate patients about the increased risk of CVST and/or VTE
- reviews indicate no increased incidence of miscarriage after the previous CVST
no clear consensus exists on the prophylactic administration of LMWH during pregnancy and puerperium; data are weak and mostly from observational studies
- prophylactic LMWH seems appropriate (unless contraindicated or full anticoagulation is indicated) (ESO guidelines 2017)
- in the U.S., LMWH is administered from the 3rd trimester to the 8th week postpartum
patients on warfarin should plan pregnancy with a switch to LMWH (due to warfarin´s teratogenicity)

optimal duration of antiseizure medication (ASM) is unknown
risk of epilepsy is approx. 5-11% (higher in patients with parenchymal hemorrhages and focal neurological deficits)
- most late-onset seizures occur within the first year
- late-onset seizures are more common in patients with early symptomatic seizures
duration should be guided by the presence and extent of parenchymal lesions, EEG findings, and the timing of epileptic seizures (early x late)
no strict recommendation; an individualized approach is advised to avoid unnecessary long-term ASM use
- isolated symptomatic seizure (<2 weeks after CVT onset) without parenchymal lesion ⇒ AED therapy can be gradually tapered within 2-4 weeks after the acute phase
- isolated symptomatic seizure or multiple ASS with parenchymal lesion and/or pathological EEG ⇒ continue ASM treatment for up to 12 months
- post-CVT epilepsy (at least two seizures > 2 weeks after CVT onset) ⇒ long-term ASM is reasonable

anxiety
depression (SSRI)
vascular cognitive deficit or impaired symbolic functions in patients with parenchymal lesions

up to 14% of patients experience chronic headache
for atypical presentation or intensity, thrombosis recurrence must be excluded (CT/MR venography + D-Dimer)