Homozygous Antithrombin Deficiency in Adolescents Presenting With Lower Extremity Thrombosis and Renal Complications

Abstract

We present 2 cases of lower extremity deep venous thrombosis in 2 gypsy adolescents from related families. The patients had low antithrombin activity levels and inherited homozygous antithrombin deficiency was confirmed by molecular analysis (Leu131Phe mutation). One patient had a history of nephrectomy at the age of 9 due to nonfunctioning kidney and 2 siblings died at 4 months of age. His mother had 3 fetal losses in the third trimester. The other propositus had an elder sister who suffered from postpartum deep vein thrombosis and pulmonary embolism. Heterozygous mutation was demonstrated in both parents.

Antithrombin deficiency in pregnancy

“…However, few published cases of patients with homozygous mutations in the heparin-binding site (HBS) have suggested that homozygosity results in an earlier presentation of thrombotic disease 12. Moreover, the replacement of threonine-85 (Thr-85) methionine (known as antithrombin-Wibble) results in a mild adult-onset thrombotic disease, whereas replacement of the same Thr-85 by lysine (known as antithrombin-Wobble) results in early childhood onset of thrombosis 12…”

Exploring antithrombin: insights into its physiological features, clinical implications and analytical techniques

“…In heterozygous form, VTE can manifest in early adolescence or younger adulthood [41], and patients with inherited thrombophilia remain at a heightened risk of VTE throughout their lifetime [4,42]. Based on antithrombin functional activity and quantity, inherited antithrombin deficiency is categorized into two types: Inherited type I antithrombin deficiency and inherited type II antithrombin deficiency [43,44].…”

A rare case of unprovoked venous thromboembolism manifestation in a young patient with antithrombin Type IIB deficiency combined with inferior vena cava anomaly from Lithuania

“…It was first described in 1965 in a Scandinavian family [1]. Inherited AT de ciencies are uncommon, with prevalence in the general healthy population being 1 in 5000 and in patients with a history of thrombosis 1 in 500 [2,3]. Most of patients have quantitative type I deficiency associated with proportional decrease of protein activity and antigen levels while type II is a qualitative deficiency leading to discrepancy between AT activity and antigen levels and causing dysfunction of the protein.…”