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.

Antithrombin deficiency and decreased protein C activity in a young man with venous thromboembolism: a case report / 医学前沿

Antithrombin and protein C are two crucial members in the anticoagulant system and play important roles in hemostasis. Mutations in SERPINC1 and PROC lead to deficiency or dysfunction of the two proteins, which could result in venous thromboembolism (VTE). Here, we report a Chinese 22-year-old young man who developed recurrent and serious VTE in cerebral veins, visceral veins, and deep veins of the lower extremity. Laboratory tests and direct sequencing of PROC and SERPINC1 were conducted for the patient and his family members. Coagulation tests revealed that the patient presented type I antithrombin deficiency combined with decreased protein C activity resulting from a small insertion mutation c.848_849insGATGT in SERPINC1 and a short deletion variant c.572_574delAGA in PROC. This combination of the two mutations was absent in 400 healthy subjects each from southern and northern China. Then, we summarized all the mutations of the SERPINC1 and PROC gene reported in the Chinese Han population. This study demonstrates that the combination of antithrombin deficiency and decreased protein C activity can result in severe VTE and that the coexistence of different genetic factors may increase the risk of VTE.

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.

Perioperative Management of Anticoagulation Therapy in a Case with Inherited Antithrombin Deficiency Receiving Aortic Valve Replacement / 日本心臓血管外科学会雑誌

A 72-year-old woman was admitted to our department with a diagnosis of severe aortic stenosis was also diagnosed Inherited antithrombin deficiency was also diagnosed after she suffered from a pulmonary thromboembolic event 10 years previously and had been taking warfarin since then. On admission, her antithrombin activity was 53% of normal, and her PT-INR level was maintained around 2.5. Preoperative management of anticoagulation therapy included discontinuation of warfarin, and supplementation of antithrombin with heparin infusion. On the day of operation, antithrombin activity was maintained above 80% by administering antithrombin, and aortic valve replacement with a mechanical valve prosthesis was carried out under standard cardiopulmonary bypass support using heparin. Heparin infusion was continued with antithrombin supplementation until PT-INR recovered to round 2.5 with warfarin. Her intra- and postoperative courses did not show any thromboembolic events, and she was discharged 14 days after the surgery.