Congenital antithrombin deficiency in patients with splanchnic vein thrombosis

Abstract

Background and aims Splanchnic vein thromboses (SVT) are a rare condition that can be life‐threatening. The most severe thrombophilia associated to SVT is antithrombin (AT) deficiency, usually caused by SERPINC1 mutations. Although transitory AT deficiencies and congenital disorders of the N‐glycosylation pathways (CDG) have been recently reported as causes of AT deficiency, the current AT clinical screening still only includes anti‐FXa activity. This study aims to (a) improve the detection of AT deficiency in SVT and (b) characterize the features of AT deficiency associated with SVT. Methods The study was performed in 2 cohorts: (a) 89 SVT patients with different underlying etiologies but in whom AT deficiency had been ruled out by classical diagnostic methods; and (b) 271 unrelated patients with confirmed AT deficiency and venous thrombosis. AT was evaluated by functional (anti‐FXa and anti‐FIIa) and immunological methods (ELISA, crossed immunoelectrophoresis, western blot), and SERPINC1 sequencing was performed. Results In 4/89 patients (4.5%) additional alterations in AT were found (two had SERPINC1 mutations, one had a specific variant causing transient AT deficiency and one patient had CDG). In 11 of the 271 patients (4.1%) with AT deficiency and thrombosis, thrombosis was located at the splanchnic venous territory. Conclusions Antithrombin deficiency may be underdiagnosed by current clinical screening techniques. Therefore, a comprehensive AT evaluation should be considered in cases of rethrombosis or doubtful interpretation of anti‐FXa activity levels. SVT is a relatively common localization of the thrombotic event in patients with congenital AT deficiency.

Antithrombin Deficiency: Frequency in Patients with Thrombosis and Thrombophilic Families

“…Frequency of AT deficiency was found in 1% in our cohort with splachnic thrombosis, which was lower in comparison with 4.5% found in a similar size of cohort (17).…”

Antithrombin deficiency as a still underdiagnosed thrombophilia: a primer for internists

“…Deep venous thrombosis, with or without complicated pulmonary embolism, is the most frequent manifestation noted so far (up to 75% of events), but thrombosis may also develop more likely in atypical venous territories such as splanchnic veins (including Budd--Chiari syndrome), the vena cava system, and cerebral sinuses. [45][46][47][48] A family history of thrombosis is an evidently strong indicator of a severe, inherited prothrombotic state. Then, even in the absence of molecular determination, a positive family history translates to severe hypercoagulability, which may be treated with antithrombotic therapy.…”

Direct oral anticoagulants for the treatment of splanchnic vein thrombosis: A state of art

“…Inherited thrombophilic disorders could be detected in about 20% of cases[ 16 ]. The most common clotting factor alteration is factor V Leiden mutation (8% of cases), followed by G20210A prothrombin mutation and antithrombin deficiency (5% of cases each); protein S and protein C deficiency are less frequent (less than 2% and 1%, respectively)[ 25 - 27 ].…”