HOMOZYGOUS VARIANT OF ANTITHROMBIN WITH LACK OF AFFINITY FOR HEPARIN - MANAGEMENT OF SEVERE THROMBOTIC COMPLICATIONS ASSOCIATED WITH INTRAUTERINE FETAL DEMISE

Patients with homozygous heparin-binding-site (HBS) qualitative antith rombin deficiencies are at significant risk of venous and arterial thr ombosis. We report on the eighth case of homozygous HBS deficiency, an d the fourth case concerning the Arg 47-Cys mutation. The proposita is a 25 year old, without known thrombotic antecedent, despite an oral c ontraceptive therapy for 7 years. After 25 weeks of a first pregnancy, she presented an intrauterine fetal demise complicated with deep vein thrombosis and pulmonary embolism. Heparin therapy was inefficient (n o clinical nor angiographic improvement, no biological hypocoagulabili ty). Heparin cofactor activity was < 10%, antigen concentration was no rmal. The crossed immunoelectrophoresis of patient's plasma, with and without heparin, showed a typical profile of qualitative HBS antithrom bin deficiency. The molecular analysis revealed an homozygous Arg 47-C ys mutation. Antithrombotic therapy was achieved with continuous infus ion of antithrombin concentrates (80 IU/kg/day) and unfractionated hep arin (500 IU/kg/day) during 12 days, leading to clinical improvement, and followed by treatment with vitamin K antagonists. This observation emphasizes the risk of intrauterine fetal demise and the inefficiency of heparin therapy without antithrombin infusion in type II HBS homoz ygous deficiency. The management of a future pregnancy will probably r equire repeated infusions of antithrombin.