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Objective: Antithrombin (AT) plays a critical role in the coagulation system, and its deficiency induces hypercoagulability. AT deficiency is caused not only by inherited variants in the SERPINC1 gene but also by acquired conditions. Therefore, AT deficiency alone could not ensure the presence of the SERPINC1 mutation. We evaluated the utility of the SERPINC1 gene test in ischemic stroke, an important clinical type of arterial thrombosis. Methods: This retrospective, observational study investigated symptomatic patients who underwent the SERPINC1 gene test because of decreased AT activity (<80%) during 2009-2021 at a tertiary hospital. For the detection of sequence variants in the SERPINC1 gene, direct Sanger sequencing and multiplex ligation-dependent probe amplification were performed. The phenotypes of patients with SERPINC1 gene mutations were examined, and the conditions associated with the pathogenic variants were analyzed. Results: In our cohort (n = 19), 13 of 19 patients (68.4%) had the pathogenic variant of the SERPINC1 gene. Ischemic stroke (n = 7) was significantly associated with the pathogenic variants (p = 0.044), and the pathogenicity detection rate was 100%. For any kind of arterial thrombosis (n = 8), the detection rate of the pathogenic variant was 87.5%, but was not statistically significant (p = 0.177). The detection rates of the pathogenic variant in ischemic stroke or arterial thrombosis groups were both higher than those in the venous thrombosis-only group (54.5%). Conclusion: The SERPINC1 gene test was useful in determining the cause of AT deficiency-related arterial thrombosis, especially ischemic stroke. We propose the diagnostic flow of SERPINC1 -related ischemic stroke. [ABSTRACT FROM AUTHOR]

ObjectiveAntithrombin (AT) plays a critical role in the coagulation system, and its deficiency induces hypercoagulability. AT deficiency is caused not only by inherited variants in the SERPINC1 gene but also by acquired conditions. Therefore, AT deficiency alone could not ensure the presence of the SERPINC1 mutation. We evaluated the utility of the SERPINC1 gene test in ischemic stroke, an important clinical type of arterial thrombosis.MethodsThis retrospective, observational study investigated symptomatic patients who underwent the SERPINC1 gene test because of decreased AT activity (

Optimal diagnosis and management of stroke in young adults benefit from a multidisciplinary team, including a vascular neurology specialist. In addition to the 'standard' vascular risk factors including smoking, hypertension, diabetes, and hyperlipidemia, one needs to consider alternative etiologies including substance abuse, carotid/vertebral artery dissections, and rare genetic conditions among others. Once a young patient is determined to have had a stroke, the next question a clinician should ask is why did this patient have a stroke? A 'heart to head' diagnostic approach is recommended. A thorough history is performed, including a detailed family history with specific annotations on each family member. A thorough physical examination is necessary including a careful evaluation of the patient's general appearance, noting any joint laxity, and/or abnormalities of the skin, eyes, and heart. Findings across multiple organ systems in the patient and/or their family may indicate a genetic etiology. After an initial head CT rules out hemorrhagic stroke, additional testing should include a brain MRI, neck and cerebral vascular imaging (e.g., CTA for head and neck), transthoracic echocardiogram with a bubble study, telemetry monitoring, basic risk factor blood work (e.g., lipid panel, hemoglobin A1c, TSH, ESR, CRP, RPR, HIV, and toxicology screen), and, when appropriate, sickle screen and pregnancy test. There should be a low threshold to obtain blood cultures or a lumbar puncture. The acute treatment of ischemic stroke in young adult patients does not differ from treatment of older adults, using intravenous alteplase within 4.5 h, assuming no contraindications. In suspected proximal large artery occlusive disease, interventional clot extraction procedures should be employed in patients deemed eligible. Long-term secondary prevention strategies aimed to reduce recurrent stroke risk by targeting and modifying vascular risk factors should be instituted. The mainstay of preventative therapy is aspirin for most etiologies; however, for atrial fibrillation, anticoagulation is recommended. Statin therapy is another pharmacologic intervention recommended in most stroke patients. Other measures employed are blood pressure reduction, smoking cessation, optimal glucose control in diabetic patients, the initiation of a healthy diet and regular exercise, and lastly, substance abuse counseling in appropriate patients. [ABSTRACT FROM AUTHOR]