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[口服避孕药与血栓形成风险:血栓形成倾向筛查试验的价值]

[Risk of thrombosis with oral contraceptives: value of a thrombophilia screening test].

作者信息

Bauersachs R, Kuhl H, Lindhoff-Last E, Ehrly A M

机构信息

I. Medizinische Klinik, Schwerpunkt Angiologie, Klinikum der Johann Wolfgang Goethe Universität, Frankfurt.

出版信息

Vasa. 1996;25(3):209-20.

PMID:8967151
Abstract

Oral contraceptives increase the natural incidence of venous thrombosis of 1-2/10,000 women per year 3- to 4-fold. Recent studies have shown that desogestrel or gestodene containing formulations bear twice the risk of older low-dose ovulation inhibitors. During pregnancy, the incidence of thrombosis rises to 10/10,000 women-years and post partum up to 40/ 10,000. For 60% of thromboses no causal explanation can be found. In approximately 40% of the patients an inherited thrombophilia can be presumed. Among the hereditary types of thrombophilia, a resistance to activated protein C (APC-resistance) represents nearly 50%, while in 15 to 20% a deficiency of antithrombin III, protein C or protein S is found. APC-resistance, with a prevalence of 3-5% in the general population, increases the risk of thrombosis 8-fold and in users of oral contraceptives 35-fold. Antithrombin III-deficiency carries a comparable risk. Protein C-deficiency increases the risk of thrombosis 9-fold and in users of oral contraceptives 15-fold. Ovulation inhibitors do not influence the risk of thrombosis in women with protein S-deficiency. Anti-phospholipid-antibodies increase during treatment with oral contraceptives and represent a considerably enhanced risk of thrombosis. Inherent thrombophilia is suspected in a patient with a positive history or family history of thrombosis, especially with thrombosis before the age of 40 or with atypical localisation. Even in these risk groups, the cost-benefit ratio of selective screening is unfavorable, as today at most 70% of the hereditary thrombophilias can be diagnosed by laboratory analysis, and only very few of the patients will actually experience a thrombotic event: only 3 of 1000 carriers of APC-resistance will suffer from thrombosis during oral contraception. On the other hand, a negative result of laboratory tests does not exclude a hereditary thrombophilic disorder. At present, it is unclear whether a selective screening process is superior to a careful assessment of individual and family history. A general screening, however, cannot be justified because of the unfavorable cost/benefit ratio. If the individual or family history or pathological laboratory parameters indicate an increased risk of thrombosis, this risk has to be carefully weighed against the consequences of discontinuation of pill use. Those few individuals with risk factors who will experience a thrombo-embolic event, cannot be identified in advance. If oral contraceptives represent a particularly high risk in patients with thrombophilic disorders and/or other risk factors, other contraceptive methods should be considered. If a patient with risk factors decides on the use of oral contraceptives, she must be informed that in the case of symptoms indicating a thrombosis, a physician should be consulted immediately. The earlier an appropriate therapy is initiated, the more effectively pulmonary thrombo-embolism and permanent damage, such as the post-phlebitic syndrome, can be prevented.

摘要

口服避孕药使每年每10000名女性中静脉血栓形成的自然发生率增加3至4倍,达到1 - 2/10000。最近的研究表明,含去氧孕烯或孕二烯酮的制剂发生血栓的风险是较老的低剂量排卵抑制剂的两倍。在怀孕期间,血栓形成的发生率上升至每10000名女性 - 年中有10例,产后则高达每10000名中有40例。60%的血栓形成找不到病因。大约40%的患者可推测存在遗传性血栓形成倾向。在遗传性血栓形成倾向类型中,对活化蛋白C的抵抗(APC抵抗)占近50%,而15%至20%的患者存在抗凝血酶III、蛋白C或蛋白S缺乏。APC抵抗在普通人群中的患病率为3 - 5%,会使血栓形成风险增加8倍,在口服避孕药使用者中增加35倍。抗凝血酶III缺乏具有类似风险。蛋白C缺乏使血栓形成风险增加9倍,在口服避孕药使用者中增加15倍。排卵抑制剂对蛋白S缺乏的女性发生血栓的风险没有影响。口服避孕药治疗期间抗磷脂抗体增加,这意味着血栓形成风险显著提高。有血栓形成阳性病史或家族史的患者,尤其是40岁之前发生血栓或血栓部位不典型者,怀疑存在先天性血栓形成倾向。即使在这些风险人群中,选择性筛查的成本效益比也不理想,因为目前通过实验室分析最多只能诊断出70%的遗传性血栓形成倾向,而且只有极少数患者会实际发生血栓事件:每1000名APC抵抗携带者中只有3人在口服避孕药期间会发生血栓。另一方面,实验室检查结果为阴性并不能排除遗传性血栓形成障碍。目前尚不清楚选择性筛查过程是否优于对个人和家族史的仔细评估。然而,由于成本效益比不佳,无法证明进行全面筛查是合理的。如果个人或家族史或病理实验室参数表明血栓形成风险增加,必须仔细权衡这种风险与停用避孕药后果之间的关系。那些少数有风险因素且会发生血栓栓塞事件的个体无法提前识别。如果口服避孕药在有血栓形成倾向疾病和/或其他风险因素的患者中风险特别高,应考虑其他避孕方法。如果有风险因素的患者决定使用口服避孕药,必须告知她如果出现提示血栓形成的症状,应立即咨询医生。开始适当治疗越早,预防肺血栓栓塞和永久性损伤(如血栓后综合征)就越有效。

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