CEREBRAL VENOUS SINUS THROMBOSIS

General therapy and acute anticoagulation in cerebral venous thrombosis

David Goldemund M.D.
Updated on 12/03/2024, published on 08/04/2021

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

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 gastrointestinal (GI) bleeding is either a preexisting lesion or a newly developed “stress ulcer
    • this condition involves disruption of the integrity of the upper GI mucosa due to extreme physiologic stress, typically in critically ill patients
    • often develops within a few hours after the initial insult
    • may result in bleeding or perforation ⇒ ↑ mortality and intensive care stay
    • the incidence is ~ 3% with prophylactic medication
  • it is important to assess each patient’s individual risk for GI complications before starting prevention. Not all hospitalized patients, including those in the ICU, require stress ulcer prophylaxis
  • risk factors for GI bleeding
    • coagulopathies, including iatrogenic
    • history of GI bleeding/peptic ulcer
    • mechanical ventilation > 48 hours
    • traumatic brain/spinal cord injury
    • sepsis
    • corticosteroid use
    • renal and hepatic impairment
    • malignancy
    • severe trauma or burns
    • severe stroke
  • initiate enteral nutrition as soon as possible!
  • prophylaxis should be administered only to patients at increased risk and should be discontinued as soon as possible (to reduce the risk of complications, such as nosocomial pneumonia, Clostridium difficile infection, drug interactions, and hepatotoxicity)
  • routine use of PPIs does not reduce mortality
  • proton pump inhibitors (PPIs)

PANTOPRAZOLE OMEPRAZOLE

  • PPIs are more expensive and significantly more effective than H2-blockers [Buendgens, 2016]
  • histamine-2 blockers if PPIs are contraindicated

FAMOTIDINE 

  • PO: 40 mg once daily or 20 mg twice daily; maintenance therapy is 20 mg orally once daily
  • IV: 20 mg twice daily, IV injection over 5 minutes or infusion over 15 minutes (+100ml of D5W)
  • adjustments are necessary for patients with renal impairment
  • sucralfate forms a protective barrier at the ulcer site. It adheres to the ulcer surface, especially in an acidic environment, creating a physical barrier that protects the ulcer from further damage by gastric acid and pepsin

SUCRALFATE

  • 1g PO or via nasogastric tube every 6-8 hours on an empty stomach; treatment usually continues for 4 to 8 weeks
  • used in the prevention and treatment of peptic ulcer disease or to reduce hyperphosphatemia
  • dose adjustment is needed in renal impairment (due to potential aluminum accumulation)
  • it is beneficial to combine analgesics with anxiolytics; consider regular administration every 6-8 hours
  • peroral analgesics:
    • ACETAMINOPHEN/PARACETAMOL
    • METAMIZOLE
    • TRAMADOL
  • intravenous analgesics:
    • ACETAMINOPHEN/PARACETAMOL
      • 500-1000 mg IV every 6-8 hours
      • max dose: 4 g/day

    • DOLSIN
    • TRAMADOL
    • SUFENTANIL
  • seizures in the acute phase are termed Acute Symptomatic Seizures (ASS)
    • ASSs occur in close temporal association with an acute brain or a systemic disturbance
  • seizures increase intracranial pressure and may potentiate secondary brain injury
  • anti-seizure medications (ASMs) are indicated for all patients after the first seizure  (ESO guidelines 2017)
  • prophylactic treatment in the first 7-14 days after diagnosis of CVST may be considered (based on the ICSVT study cohort results)
    • patients with hemiparesis and parenchymal lesions are at higher risk for ASS
    • prophylactic treatment does not lower 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
    • phenytoin (PHE) has potential interactions with anticoagulants
    • for long-term medication, consider carbamazepine (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
    • monitor serum osmolality with a target range typically 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

ACETAZOLAMIDE  (Diamox)

    • consider in cases of severe headache or visual compromise  ESO guidelines 2017
    • dosing generally starts at 250-500 mg orally, 1-4 times daily
      • dosage adjustments may be necessary for patients with renal impairment
    • monitoring of serum electrolytes is recommended due to the risk of metabolic acidosis
  • 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 cases of severe, refractory intracranial hypertension
  • actively search for and treat any infection potentially causing thrombosis
    • a facial furuncle could be the source of cavernous sinus thrombosis
    • in cases of sigmoid and transverse sinus thrombosis, look for concomitant middle ear inflammation (such as otitis media)

Anticoagulation in the acute stage

  • the objectives of anticoagulation therapy in CVT are to:
    • prevent thrombus growth
    • facilitate spontaneous fibrinolytic activity
    • prevent recurrent VTE events
  • the presence of ischemia or secondary hemorrhage is not a contraindication to anticoagulant therapy (ESO guidelines 2017)
  • anticoagulant therapy is effective in most cases; however, in case of extensive thrombosis, it may not be sufficiently fast and effective → 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 (AHA guidelines, 2024)
      • practical administration
      • more predictable anticoagulation effect
      • lower risk of thrombocytopenia
    • LMWH is also advised during pregnancy and puerperium (AHA guidelines, 2024)
    • in unstable patients, heparin may be preferable as it can be more easily discontinued 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. if a surgical procedure is anticipated )

ENOXAPARIN 1mL/10000IU/100mg (CLEXANE / LOVENOX / INHIXA)

NADROPARIN 1mL/9500IU (FRAXIPARINE)
  • target anti-Xa levels: 0.5-1 kIU/l
  • administer for 5-10 days; after clinical stabilization, switch to warfarin or DOAC (AHA guidelines, 2024)
  • in pregnancy, continue until delivery, then either continue with LMWH or switch to warfarin/DOAC
  • take care of contraindications (reduce dose in renal insufficiency, etc.)
  • DOACs are not recommended for treatment in the acute stage
  • CVT-RESPECT trial suggests that dabigatran has similar outcomes to warfarin in the subacute stage  [Ferro, 2019]
  • similar results of DOACs and VKA were also reported in the ACTION-CVT trial
  • it is reasonable to switch to DOAC or VKA after a period of lead-in parenteral anticoagulation, but whether 5 to 15 days is
    a safer or more effective strategy than shorter periods is not known (AHA guidelines, 2024)
  • DOACs are not suitable:
    • in women who are pregnant or breastfeeding
    • in individuals with antiphospholipid antibody syndrome

→ Direct oral anticoagulants (DOACs)

Vaccine-induced thrombosis (VITT) management

  • limited data, therapy requires the cooperation of a neurologist and a hematologist
  • approach similar to HIT (Heparin-Induced Thrombocytopenia)
  • IVIG 1g/kg for 2 days  (AHA guidelines, 2024)  [Furie, 2021]
    • no hard data; however, IVIG is recommended for severe, refractory cases of HIT
    • before starting therapy, get blood samples for PF4 antibody testing
  • anticoagulation
    • do not administer heparins and warfarin
    • in the acute phase, apply parenteral non-heparin agents (argatroban, fondaparinux )
      • in therapeutic dose, adjust if severe thrombocytopenia (< 20,000/mm3) or low fibrinogen
    • then switch to DOAC
  • some authors also recommend corticosteroids
  • do not administer platelet transfusions unless absolutely necessary (e.g., in patients with a very high risk of bleeding, such as after cardiothoracic surgery, in cases of manifest bleeding)

FAQs

  • the initial treatment for CVT typically involves anticoagulation therapy, even if there is bleeding in the brain. This usually starts with heparin (unfractionated heparin or low-molecular-weight heparin) administered intravenously or subcutaneously
  • yes, anticoagulation is generally considered safe and is the recommended treatment in CVT even in the presence of intracranial hemorrhage. It helps to stop the progression of the thrombus, prevents new clots, and allows natural recanalization of the vessels.
  • after the initial phase of treatment with heparin, patients are often transitioned to oral anticoagulants like warfarin
  • DOACs (like dabigatran) are being studied for CVT and may be safely used instead of warfarin
  • the duration of anticoagulation therapy varies
  • it is typically continued for 3-12 months, depending on factors like the underlying cause of the CVT, the patient’s response to treatment, and the presence of any risk factors for further clotting
  • supportive treatments include managing symptoms such as headaches, seizures, and increased intracranial pressure
  • this can involve pain relief medications, anti-seizure medications, and measures to reduce intracranial pressure
  • pregnancy-related CVT is treated similarly with anticoagulation; LMWH is preferred due to its safety profile in pregnancy
  • the management should be coordinated with a multidisciplinary team, including obstetricians

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General therapy and acute anticoagulation in cerebral venous thrombosis
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