Background: Agenesis of inferior vena cava is a rare congenital malformation with unknown etiology, although the potential role of thrombotic events during embryogenesis has been suggested.

Aims: The identification of inferior vena cava agenesis (Figure 1) in a case with early idiopathic venous thrombosis and antithrombin deficiency caused by the homozygous c.391C>T variant in SERPINC1 (p.Leu131Phe, antithrombin Budapest 3), the most severe viable thrombophilia, encouraged to evaluate the potential role of this very rare homozygous type II deficiency in this vascular abnormality.

Methods: Two large cohorts (Spain, N=313 and Hungary, N=281) of unrelated patients with congenital antithrombin deficiency (biological and genetically characterized) were enrolled. Image analysis included computed tomography (CT) and cavography/ phlebography.

Results: We recruited the worldwide largest cohort of patients with homozygote Budapest 3 variant (N=59, 10 from 7 Spanish families and 49 from 40 Hungarian families). In 12 out of 21 cases with available CT, inferior vena cava agenesis was identified, and four of them had additional anatomic defects: hypoplasia of one or both iliac veins (N=3) and renal and adrenal agenesis (N=1). Moreover, one additional case had atresia of the left iliac vein. Compensatory mechanisms, such as dilation of azygos/ hemiazygos veins or double inferior vena cava, were observed (Table 1).

Conclusions: This study shows a strong association between a specific genetic defect, homozygous SERPINC1 c.391C>T, responsible for a very severe thrombophilic state, with an embryonic congenital malformation, inferior vena cava system agenesis, identified in 62% of carriers. The impaired control of thrombin generation might facilitate intrauterine or perinatal thrombosis in this localization. Moreover, the high risk of thrombosis described in patients with this congenital malformation might be explained by the underlying thrombophilia. These data encourage the search for severe thrombophilic states and to consider the use of antithrombotic prophylaxis at risk situations in patients with these vascular defects.
ISCIII&FEDER-PI18/00598;FundaciónSéneca-19873/GERM/15

[Figure 1. Axial CT (A), 3D scan (B) and flebograhy (C,D) supporting inferior vena cava agenesis (yellow arrow) and compensatory mechanisms]

[Table 1. Characteristics of homozygous carriers of the Budapest 3 variant evaluated by CT analysis]

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ISTH Congress Abstracts - https://abstracts.isth.org/abstract/homozygous-antithrombin-budapest-3-deficiency-causes-inferior-vena-cava-system-agenesis/