Arterial thrombosis in homozygous antithrombin deficiency.

UNLABELLED: Antithrombin (AT), a serin protease inhibitor (serpin) produced in the liver, inhibits mainly thrombin and factor Xa. Antithrombin deficiency (AD) is associated with a higher incidence of thrombosis.

CASE REPORT: We report a newborn with uncomplicated birth in the 40+5 week of gestation and postnatal appearance of a reticular, livide haematoma on the right upper arm and a tonic clonic epileptic seizure. Clinical examination revealed weak pulses in the A. radialis and ulnaris. MRI scan showed a large thrombus in the A. carotis interna and externa with large cerebral infarction and a thrombus in the A. subclavia. Laboratory work up showed elevated D-dimers and antithrombin levels <20% (lowest 15%), age-related values for protein C, protein S, plasminogen, and no other inherited thrombophilia.

THERAPY: We started anticoagulation with unfractionated heparin intravenously (aPTT: 50-60 s) and under suspicion of an AD the substitution of AT (70 U/kg body weight). In course of time we changed anticoagulation to low molecular weight heparin (Anti Xa 0.6-0.8 U/ml) and substitution of 250 E/kg AT every second day. In the molecular work up we found a homozygous missense mutation in exon 2 of SERPINC1 gene (type "Budapest 3"). Molecular analysis showed also heterozygous mutations in both parents and a homozygous mutation in the asymptomatic brother aged three years. At age of six months we changed the anticoagulation to coumadin (INR 2.5-3.5). Anticoagulation with coumadin was also started in the brother.

DISCUSSION: Hereditary AD is associated with an increased risk of thrombosis. The homozygous status mainly leads to intrauterine fetal loss or the occurrence of peri- and postnatal thrombosis. Therapy consists in the substitution of AT and a lifelong anticoagulation with vitamin K antagonists also in asymptomatic patients.