Homozygous variant of antithrombin with lack of affinity for heparin: management of severe thrombotic complications associated with intrauterine fetal demise.
Homozygous variant of antithrombin with lack of affinity for heparin: management of severe thrombotic complications associated with intrauterine fetal demise.
复制标题
缺乏肝素亲和力的抗凝血酶纯合变体：与宫内胎儿死亡相关的严重血栓并发症的治疗。
DOI：
10.1097/00001721-199610000-00008
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发表时间：
1996
期刊：
影响因子：
--
通讯作者：
B. Jude
中科院分区：
文献类型：
--
作者：
A. Bauters;C. Zawadzki;A. Bura;C. Théry;A. Watel;D. Subtil;M. Aiach;J. Emmerich;B. Jude
纯合子肝素结合位点（HBS）定性抗凝血酶缺乏的患者有静脉和动脉血栓形成的显著风险。我们报道了第8例纯合子HBS缺乏症，第4例关于Arg 47-Cys突变的病例。申请人为25岁，尽管口服避孕药治疗7年，但没有血栓病史。在第一次怀孕25周后，她出现了宫内胎儿死亡并伴有深静脉血栓形成和肺栓塞。肝素治疗无效（无临床和血管造影改善，无生物低凝性）。肝素辅助因子活性< 10%，抗原浓度正常。患者血浆的交叉免疫电泳，无论是否使用肝素，显示出典型的定性HBS抗凝血酶缺乏症。分子分析显示为精氨酸4-胱氨酸纯合突变。通过连续输注抗凝血酶浓缩物（80 IU/kg/天）和未分级肝素（500 IU/kg/天）12天实现抗血栓治疗，导致临床改善，随后使用维生素K拮抗剂治疗。这一观察结果强调了II型HBS纯合缺乏症患者宫内胎儿死亡的风险和不输注抗凝血酶的肝素治疗的低效率。未来妊娠的管理可能需要反复输注抗凝血酶。
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.