Coexistence of antithrombin deficiency and suspected inferior vena cava atresia in an adolescent and his mother – case report and clinical implications

Abstract

Background Antithrombin deficiency (ATD) is an autosomal dominant thrombophilia presenting with varying phenotypes. In pediatric patients with ATD, thrombosis typically develops during the neonatal period or adolescence. However, to date there are no consistent recommendations on the therapeutic management of children with ATD. Inferior vena cava atresia (IVCA) belongs to a range of congenital or acquired vena cava malformations and is described as an independent risk factor for thrombosis. The present case report explores two cases of combined ATD and IVCA in an adolescent and his mother. Case presentation A 14-year-old male presented with extensive deep venous thromboses (DVTs) of both lower extremities as well as an IVCA. The patient had previously been diagnosed with an asymptomatic ATD without therapeutic consequences at that time. His mother was suffering from an ATD and had herself just been diagnosed with IVCA, too. The DVTs in the adolescent were treated by systemic anticoagulation and catheter-directed local thrombolysis causing favourable results. Yet, despite adequate oral anticoagulation the DVTs in both lower extremities reoccurred within 1 week after the patient was discharged from hospital. This time, thrombolysis could not be fully achieved. Surprisingly, probing and stenting of the IVCA was achieved, indicating an acquired IVCA which could have occurred after undetected thrombosis in early childhood. Genetic analyses showed the same mutation causing ATD in both son and mother: heterozygote missense mutation c.248 T > C, p.(Leu83Pro), within the heparin binding domain of antithrombin. This mutation was never reported in mutation databases before. Conclusions To our knowledge this is the first case report discussing combined ATD and IVCA in two family members. Since ATDs present with clinical heterogeneity, taking a thorough family history is crucial for the anticipation of possible complications in affected children and decisions on targeted diagnostics and therapeutic interventions. Affected families must be educated on risk factors and clinical signs of thrombosis and need an immediate diagnostic workup in case of clinical symptoms. IVCA in patients with ATD could occur due to thrombotic occlusion at a very early age. Therefore, in case of family members with IVCA and ATD ultrasound screening in newborns should be considered.

Identification and characterization of two SERPINC1 mutations causing congenital antithrombin deficiency

“…Its clinical manifestations are severe and usually associated with severe mutations in SER-PINC1, which lead to a significant decrease in the level of AT in plasma owing to mutations that destabilize mRNA, misfolded proteins, and intracellular retention, or lead to abnormal degradation [21][22][23]. Type II mainly affects the domain function bound to thrombin or heparin, with normal plasma AT antigen content, but its activity is weakened [24], its clinical manifestations are mild, and its incidence is relatively high [25]. Moreover, the mutant forms are mostly missense mutations, which only affect the functional domain of AT [26][27][28].…”

Antithrombin Deficiency and Thrombosis: A Wide Clinical Scenario Reported in a Single Institution

“…According to these publications, ultrasound screening in newborns with relatives with IVCA and congenital AT deficiency is suggested, and early therapeutic intervention is necessary to prevent further thrombotic complications. 12 , 13 …”

“…According to these publications, ultrasound screening in newborns with relatives with IVCA and congenital AT deficiency is suggested, and early therapeutic intervention is necessary to prevent further thrombotic complications. 12,13 Age is an important risk factor for thrombosis development. Up to 60% of patients with inherited AT deficiency have thrombosis before the age of 65.…”