HOMOZYGOUS VARIANT OF ANTITHROMBIN WITH LACK OF AFFINITY FOR HEPARIN - MANAGEMENT OF SEVERE THROMBOTIC COMPLICATIONS ASSOCIATED WITH INTRAUTERINE FETAL DEMISE
A. Bauters et al., HOMOZYGOUS VARIANT OF ANTITHROMBIN WITH LACK OF AFFINITY FOR HEPARIN - MANAGEMENT OF SEVERE THROMBOTIC COMPLICATIONS ASSOCIATED WITH INTRAUTERINE FETAL DEMISE, Blood coagulation & fibrinolysis, 7(7), 1996, pp. 705-710
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.