PD Dr. Sabine Schneider (Erlangen/ DE), Robert Anton Kramer (Erlangen/ DE), Prof. Dr. Robert Zimmermann (Erlangen/ DE), PD Dr. Julian Strobel (Erlangen/ DE), Dr. Susanne Achenbach (Erlangen/ DE), Armin Michael Ströbel (Erlangen/ DE), Prof. Dr. Holger Hackstein (Erlangen/ DE), PD Dr. David Alexander Christian Messerer (Erlangen/ DE)
Background
Prothrombotic hereditary risk factors for cerebral vein thrombosis (CVT) are underinvestigated but of clinical interest to better understand the underlying pathophysiology and stratify patients for the risk of recurrence. Our exploratory study aimed to identify hereditary prothrombotic risk factors in CVT patients using next generation sequencing (NGS).
Methods
In our outpatient clinic, 183 patients presented in the years 1999-2021 with a history of CVT. An initial screening identified a number of common prothrombic risk factors, including Factor V Leiden (rs6025) and Prothrombin G20210A (rs1799963). All patients without relevant findings (58 individuals) were invited to participate in a subsequent genetic analysis of 55 relevant genes using NGS. The prevalence of the identified variants in the study population was compared with a general European population, accessing the NCBI database of Genotypes and Phenotypes Release 2.
Results
Three intron variants (ADAMTS13: rs28446901, FN1: rs56380797, rs35343655) were identified to occur with a significantly higher frequency in the CVT patient cohort compared to the general European population. Furthermore, the combined prevalence of at least two of four potentially prothrombic single nucleotide polymorphisms (SNPs) [FGA (rs6050), F13A1 (rs5985), ITGB3 (rs5918), and PROCR (rs867186)] was significantly higher for five out of six possible combinations in the CVT subjects.
Conclusion
SNPs rs6050 and rs5985 affect fibrin characteristics, rs5918 enhances fibrin binding, and rs867186 reduces the profibrinolytic effect of APC. According to a higher frequency of at least two of these variants in CVT patients, altered blood clot properties combined with increased platelet binding/reduced fibrinolysis might increase the risk for thromboembolic events, such as CVT. Identification of hereditary prothrombic variants makes NGS a valuable tool for supporting standard diagnostics.
Offenlegung Interessenkonflikt:
No coflicts of interest.