General therapy and acute anticoagulation in cerebral venous thrombosis

Created 08/04/2021, last revision 27/09/2023

  • the patient should be monitored in the Intensive Care Unit (ICU) in the acute stage
  • order bed rest with the upper body in a slightly elevated position
  • initiate general therapy and acute anticoagulation
  • investigate the underlying cause of thrombosis (e.g., hypercoagulable state, infection, etc.)
  • with extensive or progressive thrombosis, consider early endovascular treatment

General therapy

  • thanks to anticoagulant therapy, no specific strategy is necessary
  • Intermittent Pneumatic Compressions (IPC) may be added → VTE prevention
  • the most common cause of GI bleeding is either a preexisting lesion or newly developed “stress ulcer
    • disruption of the integrity of the upper GI mucosa due to extreme physiological stress, typically in critically ill patients
    • often develops within a few hours after the initial insult
    • can result in bleeding or perforation ⇒ ↑ mortality and intensive care stay
    • incidence approx. 3% when on prophylactic medication
  • risk factors for GI bleeding
    • coagulopathies, including iatrogenic
    • history of GI bleeding/peptic ulcer
    • mechanical ventilation > 48h
    • traumatic brain/spinal cord injury
    • sepsis
    • corticosteroids use
    • renal and hepatic impairment
    • malignancy
    • sever stroke
  • prophylaxis should be administered only to patients at increased risk and discontinued in a timely manner (due to the increased risk of nosocomial pneumonia, Clostridium difficile infection, drug interactions, or hepatotoxicity); routine use of PPIs does not reduce mortality
    • proton pump inhibitors (PPIs) – PANTOPRAZOLE OMEPRAZOLE
      • 20-40 mg once daily PO or IV
      • PPIs are more expensive and significantly more effective than H2-blockers [Buendgens, 2016]
    •  use H2 blockers if PPIs are contraindicated FAMOTIDINE
      • 40 mg once daily, or 20 mg twice daily PO
      • 1g PO or via nasogastric tube every 6-8 hours
      • used in peptic ulcer prevention and treatment or to reduce hyperphosphatemia
    • antacids
  • initiate enteral nutrition as soon as possible!
  • it is beneficial to combine analgesics with anxiolytics; consider regular administration every 6-8 hours
  • anxiolytics:

      bromazepam   (LEXAURIN / LECTOPAM)
      tablets:   1.5 mg / 3 mg

      • starting dose for anxiety:  1.5 mg taken 2-3 times a day
        • elderly patients may start with a lower dose
      • gradually increase until anxiety is controlled (usually 1.5-3 mg 3 times a day)
      • the usual maximum adult dose: 9 mg/day
      • discontinuation:  the drug should never be abruptly stopped but slowly tapered off under medical supervision
      • bromazepam binds to the GABA-A receptor producing a conformational change and potentiating its inhibitory effects
      • short-term treatment of insomnia, short-term treatment of anxiety or panic attacks, and the alleviation of the symptoms of alcohol- and opiate-withdrawal

      • hypersensitivity to benzodiazepines, bromazepam, or to any of the excipients
      • myasthenia gravis, severe respiratory insufficiency, sleep apnoea syndrome

      alprazolam   (NEUROL / XANAX / ALPRAZOLAM)
      tablets:   0.25 / 0.5 / 1 mg

      • starting dose for anxiety:  0.25 mg taken 2-3 times a day
        • elderly patients may start with a lower dose of 0.125 mg taken 2-3 times a day
      • gradually increase until anxiety is controlled (usually 0.2-1 mg 3 times a day)
      • the usual maximum dose: 3 mg/day
      • discontinuation:  decrease the daily dose of alprazolam by 0.25 mg every three days

      • hypersensitivity to benzodiazepines, alprazolam, or to any of the excipients
      • myasthenia gravis, severe respiratory insufficiency, sleep apnoea syndrome and severe hepatic insufficiency
      • 2.5-10 mg, taken 2-4 times daily

  • peroral analgesics:
  • intravenous analgesics:
      • 500-1000 mg IV every 6-8 hours
      • max dose: 4 g/day


      metamizole   (NOVALGIN, ANALGIN, PYRALGIN)
      ampule: 1ml / 500 mg

      • metamizole is a strong analgesic and antipyretic with spasmolytic properties
      • it has weak anti-inflammatory or antithrombotic properties

      • adults: 1-2 ampules (1-2ml/500-1000 mg) + 100 ml of NS via IV infusion over 15-30 minutes every 6-8 hours
      • maximum dose: 5 g/day

      • metamizole can lead to agranulocytosis, a life-threatening side effect where a patient’s neutrophil count falls below 500 cells per μL (dose-independent)
      • hypotension
      • risk of anafylactoid reaction
    • DOLSIN
  • seizures in the acute phase are termed as Acute Symptomatic Seizures (ASS)
    • ASS occurs at the time of a systemic insult or in close temporal association with a documented brain insult
  • seizures increase intracranial pressure and may potentiate secondary brain injury
  • antiepileptic drugs (AEDs) are indicated in all patients after the first seizure  (ESO guidelines 2017)
  • prophylactic treatment in the first 7-14 days after diagnosis of CVST may be considered (according to cohort results from the ICSVT study)
    • patients with hemiparesis and parenchymal lesions are at higher risk for ASS
    • prophylactic treatment does not reduce the risk of post-CVST epilepsy
  • choice of antiepileptic drug
    • in the acute phase, choose valproic acid (VPA) or levetiracetam (LEV), as they allow rapid parenteral titration
    • the issue with phenytoin (PHE) is possible interaction with anticoagulants
    • for long-term medication, consider CBZ, VPA, LEV

→ see intracranial hypertension treatment

    • often used as an osmotic diuretic to reduce intracranial pressure
    • initial dose: 0.25 to 1 g/kg IV, usually given as a 15-minute infusion
    • maintenance dose: 0.25 to 0.5 g/kg IV every 4-6 hours as needed, based on clinical response and serum osmolality
    • serum osmolality should be monitored, with a target range usually between 300-320 mOsm/kg
    • monitor renal function, electrolytes, and fluid balance

FUROSEMIDE (Furosemide, Lasix)

    • dose:  20-40 mg IV, with the potential for titration based on clinical response
    • monitoring of electrolytes and renal function is advised


    • consider in cases of severe headache or visual compromise  ESO guidelines 2017
    • dosing generally starts at 250 mg to 500 mg orally, twice a day
  • steroids are not recommended [Canhão, 2008]
    • steroids may be administered only in CVST associated with Behcet’s disease or other inflammatory diseases (e.g., SLE) (ESO guidelines 2017)
  • consider decompressive craniectomy for severe, refractory intracranial hypertension
  • actively search for and treat the infection that may be causing the thrombosis
    • a facial furuncle may be the source of cavernous sinus thrombosis
    • in cases of sigmoid and transverse sinus thrombosis, look for concomitant middle ear inflammation (otitis media)

Anticoagulation in the acute stage

  • the outcome for patients treated with heparin was significantly better than for those given a placebo in studies
  • the presence of ischemia or secondary hemorrhage is not a contraindication to heparin (AHA/ASA 2014 IIa/B, ESO 2017 )
  • anticoagulant therapy does not dissolve the thrombus; it prevents its growth and facilitates spontaneous fibrinolytic activity
    • rapid and good effect in smaller thrombi
    • for large thromboses, anticoagulation alone may not be a sufficiently fast and effective treatment → consider early endovascular intervention
  • non-randomized trials suggest a better outcome with LMWH compared to unfractionated heparin (UHF)
    • LMWH is preferred in clinical practice and according to guidelines (ESO 2017)
    • administer LMWH during pregnancy (ESO 2017, AHA/ASA 2014 IIa/C)
    • in unstable patients, heparin may be preferable as it is easier to discontinue treatment prior to an invasive procedure
  • 1 vial = 25000 IU/5mL
  • continuous infusion  → heparinization protocol)
  • administer for 5-10 days until the patient is clinically stable; maintain aPTT at 2-2.5x the upper limit of normal
  • in the presence of significant ischemia or secondary hemorrhage, skip bolus
  • use UFH if LMWHs are contraindicated (e.g., due to renal insufficiency) or when a rapid withdrawal is required (e.g., an anticipated neurosurgical procedure)


  • target anti Xa levels: 0.5-1 kIU/l
  • administer for 5-10 days; after clinical stabilization, switch to warfarin (DOAC may be considered)
  • in case of pregnancy, continue until delivery, then either continue with LMWH or switch to warfarin/DOAC
  • take care of contraindications (reduce dose in renal insufficiency, etc.)
  • data from case reports
  • CVT-RESPECT trial suggests that dabigatran has similar outcomes to warfarin in the subacute stage   [Ferro, 2019]
    • patients with acute CVT, who were stable after 5-15 days of treatment with parenteral heparin, were screened
    • both dabigatran and warfarin may be safe and effective for preventing recurrent VTEs in patients with CVT
  • according to ESO guidelines 2017, DOACs are not recommended for treatment in the acute stage

→ Direct oral anticoagulants (DOACs)

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General therapy and acute anticoagulation in cerebral venous thrombosis
link: https://www.stroke-manual.com/cerebral-venous-thrombosis-acute-anticoagulation/