Antithrombin deficiency caused by SERPINC1 gene mutations predispose to venous thrombotic events / 中华检验医学杂志

Objective:To analyze 12 antithrombins (AT) gene mutations that cause AT deficiency and discuss the relationship between the SERPINC1 gene. mutations and venous thrombotic events.Methods:This study belongs to case series of observational studies. Collected the clinical data of 12 AT deficiency cases in the First Affiliated Hospital of Wenzhou Medical University from April 2014 to April 2021 and collected the blood samples before treatment. The AT activity (AT: A) and AT antigen (AT: Ag) was detected by chromogenic substrate and immunoturbidimetry, respectively. The 7 exons and flanking sequences of the SERPINC1 gene were sequenced directly by PCR, the suspected mutations were validated by reverse sequencing. Analyzed the correlation between the SERPINC1 gene. mutations and venous thrombotic events and figured out the proportion.Results:The AT: A of the 12 patients all decreased significantly, ranging from 30% to 66%, and the AT: Ag of the 7 patients decreased accordingly, showing type Ⅰ AT deficiency, and the AT: Ag of the other 5 patients were normal, presented type Ⅱ AT deficiency. 12 mutations were found including 6 heterozygous mutations which were discovered for the first time: c.456_458delCTT(p.phe121del), c.318_319insT(p.Asn75stop), c.922G>T(p.Gly276Cys), c.938T>C (p.Met281Thr), c.1346T>A(p.Leu417Gln)and c.851T>C(p.Met252Thr). All 12 patients had venous thrombosis, and 3 cases including 2 compound heterozygotes and 1 single heterozygote all suffered from deep venous thrombosis (DVT) when they were younger without obvious triggers. The other 9 patients all combined with the other thrombotic factors including old age, hypertensive, smoking, pregnancy, and prolonged immobilization.Conclusion:Patients with AT deficiency caused by SERPINC1 gene defects are prone to venous thrombosis, especially combined with other thrombotic factors.

Hereditary Antithrombin Deficiency with Hemorrhagic Cerebral Infarction and Cardiac Thrombosis Occurred in Neonatal Period: A Case Report / 임상소아혈액종양

Antithrombin (AT) is the main inhibitor of blood coagulation proteases. Hereditary AT deficiency is an autosomal-dominant thrombophilic disorder caused by a SERPINC1 abnormality, it represents a risk factor for thromboembolic disease. A 25-day-old male infant was referred to Severance Children's Hospital for hemorrhagic cerebral infarction with hydrocephalus. The initial laboratory study showed 11% AT activity. An approximate 4 mm-x-3 mm-size thrombosis was also found in the right ventricle by echocardiography. We found two deletion in the coding and flanking sequences of SERPINC1 c.235C>T (p.Arg79Cys) and c.442T>C (p.Ser148Pro) at 10 months of age. The p.Ser148Pro mutation was found in his mother but the other was not. This case is a rare thrombotic event that occured early year in due to AT deficiency. Our patient had side effects after heparin treatment, so aspirin therapy was employed. No thrombotic events occurred until 1 year of age.

Hereditary Antithrombin Deficiency with Hemorrhagic Cerebral Infarction and Cardiac Thrombosis Occurred in Neonatal Period: A Case Report / 임상소아혈액종양

Antithrombin (AT) is the main inhibitor of blood coagulation proteases. Hereditary AT deficiency is an autosomal-dominant thrombophilic disorder caused by a SERPINC1 abnormality, it represents a risk factor for thromboembolic disease. A 25-day-old male infant was referred to Severance Children's Hospital for hemorrhagic cerebral infarction with hydrocephalus. The initial laboratory study showed 11% AT activity. An approximate 4 mm-x-3 mm-size thrombosis was also found in the right ventricle by echocardiography. We found two deletion in the coding and flanking sequences of SERPINC1 c.235C>T (p.Arg79Cys) and c.442T>C (p.Ser148Pro) at 10 months of age. The p.Ser148Pro mutation was found in his mother but the other was not. This case is a rare thrombotic event that occured early year in due to AT deficiency. Our patient had side effects after heparin treatment, so aspirin therapy was employed. No thrombotic events occurred until 1 year of age.