Tamoxifen-induced tissue factor pathway inhibitor reduction: a clue for an acquired thrombophilic state?
Tamoxifen-induced tissue factor pathway inhibitor reduction: a clue for an acquired thrombophilic state?
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DOI：
10.1093/annonc/mdh437
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发表时间：
2004-11-01
影响因子：
50.5
通讯作者：
Celik, I
中科院分区：
文献类型：
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作者：
Erman, M;Abali, H;Celik, I
背景资料：目前对止血系统的了解使我们能够更好地探索他莫昔芬（TAM）诱导的血栓形成素质的神秘病理学。因此，我们的目的是评估乳腺癌患者接受TAM的辅助basis.Patients和方法的止血变化：研究人群包括43名女性激素受体阳性乳腺癌患者接受TAM 20毫克/天作为其辅助治疗的一部分。平均年龄为52 ± 12岁（范围25-74岁）。21例患者（49%）为绝经前。在TAM治疗6个月之前和之后收集血浆样品，并测定总组织因子途径抑制物（TFPI）、游离TFPI、脂质结合TFPI、血栓调节蛋白、D二聚体、活化蛋白C抗性（APC res）、因子VIIa、II、V、VII和X以及总体纤溶能力（GFC）。中位总TFPI从48.5 ng/ml显著降至36.2 ng/ml（P=0.001），游离TFPI从10 ng/ml降至7.6 ng/ml（P=0.001），脂质结合TFPI从39.1 ng/ml降至28.7 ng/ml（P=0.001）。凝血因子11（P=0.03）、凝血因子V（P=0.001）、凝血因子VII（P=0.06）、血栓调节蛋白（P=0.01）和D-二聚体（P=0.001）水平显著降低。然而，APC静息时间显著延长（P=0.04）。其余参数，我们已经研究了没有显着affected.Conclusion：我们的研究结果表明，TAM往往激活凝血途径，通过抵消主要分子参与凝血抑制，即TFPI和TM。如原型GFC所反映，药物似乎会损害纤维蛋白溶解系统的预期代偿性激活，该系统可清除凝血激活产生的纤维蛋白聚合物。
Background: Current understanding of hemostatic systems enables us to better explore the enigmatic pathobiology of tamoxifen (TAM)-induced thrombotic diathesis. We have therefore aimed to assess the hemostatic changes in breast cancer patients receiving TAM on an adjuvant basis.Patients and methods: The study population consisted of 43 female patients with hormone receptor-positive breast cancer who received TAM 20 mg/day as part of their adjuvant treatment. Mean age was 52+/-12 years (range 25-74). Twenty-one patients (49%) were premenopausal. Plasma samples were collected prior to and following 6 months of TAM therapy and were assayed for total tissue factor pathway inhibitor (TFPI), free TFPI, lipid-bound TFPI, thrombomodulin, D dimer, activated protein C resistance (APC res), factors VIIa, II, V, VII and X, and global fibrinolytic capacity (GFC).Results: Median total TFPI decreased significantly from 48.5 ng/ml to 36.2 ng/ml (P=0.001), free TFPI from 10 to 7.6 ng/ml (P=0.001) and lipid-bound TFPI from 39.1 to 28.7 ng/ml (P=0.001). There were significant decreases in the levels of factor 11 (P=0.03), factor V (P=0.001), factor VII (P=0.06), thrombomodulin (P=0.01) and D dimer (P=0.001). However, APC res times were significantly prolonged (P=0.04). The remaining parameters that we have studied were not significantly affected.Conclusion: Our findings suggest that TAM tends to activate the coagulation pathway by counteracting major molecules involved in coagulation inhibition, namely TFPI and TM. As reflected by unchanged GFC, the drug appears to impair the expected compensatory activation of the fibrinolytic system, which removes fibrin polymers resulting from coagulation activation.