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Dabigatran in Cerebral Sinus Vein Thrombosis and Thrombophilia

Lukas Kellermair1,2, Matthias W G Zeller1,2, Caterina Kulyk1,2

  • 1Department of Neurology 2, Kepler University Hospital, Med Campus III, 4020 Linz, Austria.

Life (Basel, Switzerland)
|July 27, 2022
PubMed

Insights

Thrombophilia influences dabigatran levels in cerebral sinus vein thrombosis (CSVT) patients. Homozygote prothrombin mutation (PTM) significantly lowers dabigatran peak concentration, unlike heterozygote PTM or Factor V Leiden (FVL).

Area of Science:

  • Pharmacogenomics
  • Vascular Medicine
  • Thrombosis Research

Background:

  • Thrombophilic gene alterations are significant risk factors for cerebral sinus vein thrombosis (CSVT).
  • Up to 30% of CSVT patients exhibit thrombophilic defects like prothrombin mutation (PTM) or Factor V Leiden (FVL).
  • The impact of thrombophilia on dabigatran etexilate plasma levels in CSVT patients remains unclear.

Purpose of the Study:

  • To investigate the influence of thrombophilia on dabigatran peak-plasma levels in patients with CSVT.
  • To compare dabigatran levels and radiological outcomes between CSVT patients with and without genetic thrombophilia.

Main Methods:

  • Prospective case-control study monitoring 10 patients with acute CSVT and genetic thrombophilia on off-label dabigatran etexilate (150 mg twice daily) for 12 months.
  • Measurement of dabigatran peak-plasma levels and radiological outcomes.
  • Comparison with a control group of patients without genetic thrombophilia on the same dabigatran regimen.

Main Results:

  • Patients with homozygote PTM showed significantly lower dabigatran peak concentrations (23 ± 4.2) compared to FVL (152.3 ± 27.5) and control groups (159.6 ± 63.08; p ≤ 0.05).
  • No significant difference in dabigatran levels was observed between heterozygote PTM, FVL, and control groups (p = 0.29).
  • No correlation was found between dabigatran peak concentration and the rate of thrombus dissolution.

Conclusions:

  • Dabigatran peak concentration is stable in heterozygote FVL and PTM patients but not in homozygote PTM patients compared to controls.
  • Genetic screening for thrombophilia in post-CSVT patients may aid in personalized oral anticoagulation therapy decisions.
  • Tailored therapeutic strategies based on genetic screening could potentially reduce thrombotic events in CSVT patients.
Abstract

Keywords:
cerebral sinus vein thrombosisdabigatran peak concentrationfactor II mutationfactor V Leidenthrombus dissolution

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