Utility of the SERPINC1 Gene Test in Ischemic Stroke Patients With Antithrombin Deficiency

Area of Science:

• Genetics
• Hematology
• Neurology

Background:

• Antithrombin (AT) deficiency, caused by SERPINC1 gene mutations or acquired conditions, increases hypercoagulability.
• AT deficiency alone does not confirm a SERPINC1 mutation, necessitating genetic testing for accurate diagnosis.
• Ischemic stroke is a significant clinical manifestation of arterial thrombosis.

Purpose of the Study:

• To evaluate the diagnostic utility of the SERPINC1 gene test in patients with suspected antithrombin deficiency and arterial thrombosis, with a focus on ischemic stroke.
• To correlate SERPINC1 gene variants with clinical phenotypes, particularly ischemic stroke.
• To propose a diagnostic pathway for SERPINC1-related ischemic stroke.

Main Methods:

• Retrospective analysis of symptomatic patients with decreased AT activity (<80%) who underwent SERPINC1 gene testing (2009-2021).
• Utilized direct Sanger sequencing and multiplex ligation-dependent probe amplification for SERPINC1 variant detection.
• Examined patient phenotypes and analyzed conditions associated with pathogenic SERPINC1 variants.

Main Results:

• Pathogenic SERPINC1 variants were identified in 68.4% (13/19) of the cohort.
• Ischemic stroke showed a significant association with pathogenic SERPINC1 variants (100% detection rate, p=0.044).
• Arterial thrombosis overall had an 87.5% detection rate for pathogenic variants, while venous thrombosis-only cases had a 54.5% detection rate.

Conclusions:

• The SERPINC1 gene test is a valuable tool for diagnosing the cause of AT deficiency-related arterial thrombosis, especially ischemic stroke.
• The findings support the use of SERPINC1 genetic testing in the diagnostic workup of ischemic stroke patients with low AT activity.
• A proposed diagnostic flow for SERPINC1-related ischemic stroke can improve patient management.