Homozygous variant of antithrombin with lack of affinity for heparin: management of severe thrombotic complications associated with intrauterine fetal demise

Blood Coagul Fibrinolysis. 1996 Oct;7(7):705-10. doi: 10.1097/00001721-199610000-00008.

Abstract

Patients with homozygous heparin-binding-site (HBS) qualitative antithrombin deficiencies are at significant risk of venous and arterial thrombosis. We report on the eighth case of homozygous HBS deficiency, and the fourth case concerning the Arg 47-Cys mutation. The proposita is a 25 year old, without known thrombotic antecedent, despite an oral contraceptive 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 (no clinical nor angiographic improvement, no biological hypocoagulability). Heparin cofactor activity was < 10%, antigen concentration was normal. The crossed immunoelectrophoresis of patient's plasma, with and without heparin, showed a typical profile of qualitative HBS antithrombin deficiency. The molecular analysis revealed an homozygous Arg 4-Cys mutation. Antithrombotic therapy was achieved with continuous infusion of antithrombin concentrates (80 IU/kg/day) and unfractionated heparin (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 homozygous deficiency. The management of a future pregnancy will probably require repeated infusions of antithrombin.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Antithrombin III / genetics*
  • Antithrombin III / metabolism
  • Binding Sites / genetics
  • Blood Coagulation Factors / analysis
  • Female
  • Fetal Death*
  • Heparin / metabolism*
  • Heparin / therapeutic use
  • Homozygote*
  • Humans
  • Immunoelectrophoresis, Two-Dimensional
  • Pregnancy
  • Pregnancy Complications, Hematologic / blood*
  • Sequence Analysis, DNA
  • Thrombosis / blood*
  • Thrombosis / drug therapy
  • Thrombosis / genetics*

Substances

  • Blood Coagulation Factors
  • Antithrombin III
  • Heparin