Dabigatran in Cerebral Sinus Vein Thrombosis and Thrombophilia

Lukas Kellermair; Matthias W G Zeller; Caterina Kulyk; Josef Tomasits; Tim J von Oertzen; Milan R Vosko

doi:10.3390/life12070970

Dabigatran in Cerebral Sinus Vein Thrombosis and Thrombophilia

Life (Basel). 2022 Jun 28;12(7):970. doi: 10.3390/life12070970.

Authors

Lukas Kellermair^{1

2}, Matthias W G Zeller^{1

2}, Caterina Kulyk^{1

2}, Josef Tomasits^{2

3}, Tim J von Oertzen^{1

2}, Milan R Vosko^{1

2}

Affiliations

¹ Department of Neurology 2, Kepler University Hospital, Med Campus III, 4020 Linz, Austria.
² Medical Faculty, Johannes Kepler University, 4040 Linz, Austria.
³ Department of Laboratory Medicine, Kepler University Hospital, Med Campus III, 4020 Linz, Austria.

Abstract

Background and purpose: Thrombophilic gene alterations are a major risk factor for cerebral sinus vein thrombosis (CSVT). Up to 30% of all patients with cerebral sinus vein thrombosis (CSVT) are found to have thrombophilic defects such as prothrombin mutation (PTM) or factor V Leiden (FVL). Their repercussions on the plasma levels of dabigatran etexilate are unclear. In this prospective case-control study, we aimed to investigate whether thrombophilia in CSVT has an influence on dabigatran peak-plasma levels.

Methods: We monitored 10 patients over 12 months with acute CSVT, genetic thrombophilia with off-label use of dabigatran etexilate 150 mg twice a day and measured dabigatran peak-plasma levels and radiological outcome. We also monitored patients without genetic thrombophilia with dabigatran etexilate 150 mg twice a day and compared the efficiency and dabigatran peak-plasma levels.

Results: Patients with homozygote PTM had significantly lower dabigatran peak concentration compared to patients with FVL or the control group (23 ± 4.2 vs. 152.3 ± 27.5 and 159.6 ± 63.08; p-value ≤ 0.05) There was no significant difference in dabigatran etexilate plasma levels between the heterozygote PTM group compared to patients with FVL or the control group (p = 0.29). There was no correlation between dabigatran peak concentration and delayed thrombus dissolution.

Conclusions: Dabigatran peak concentration was stable in patients with heterozygote FVL and heterozygote PTM, but not in homozygote PTM, compared to controls. Genetic screening for thrombophilia in patients after CSVT may be useful to make patient tailored therapeutic decisions regarding oral anticoagulation and may decrease thrombotic events.

Keywords: cerebral sinus vein thrombosis; dabigatran peak concentration; factor II mutation; factor V Leiden; thrombus dissolution.

Grants and funding

Lukas Kellermair has received honoraria as a speaker from AbbVie GmbH and Sobi, all outside of the present study Matthias Zeller has nothing to disclose Caterina Kulyk has nothing to disclose Josef Tomasits has nothing to disclose Tim von Oertzen reports personal fees from Zogenix, Angelini Pharma, Arvelle Pharma, LivaNova, Eisia, AbbVie, Bayer, Novartis and GW Pharma, grants from Novartis, and Boehringer Ingelheim, all outside of the present study, Milan R. Vosko has received speakers honoraria from Boehringer Ingelheim, Bristol-Myers Squibb and Bayer, all outside of the present study Open Access Funding by the University of Linz.