Benigni A, Gregorini G, Frusca T, Chiabrando C, Ballerini S, Valcamonico A, Orisio S, Piccinelli A, Pinciroli V, Fanelli R
Mario Negri Institute for Pharmacological Research, Bergamo, Italy.
N Engl J Med. 1989 Aug 10;321(6):357-62. doi: 10.1056/NEJM198908103210604.
There is evidence that aspirin in low doses favorably influences the course of pregnancy-induced hypertension, but the mechanism, although assumed to involve suppression of the production of thromboxane by platelets, has not been established. We performed a randomized study of the effect of the long-term daily administration of 60 mg of aspirin (n = 17) or placebo (n = 16) on platelet thromboxane A2 and vascular prostacyclin in women at risk for pregnancy-induced hypertension. Low doses of aspirin were associated with a longer pregnancy and increased weight of newborns. Serum levels of thromboxane B2, a stable product of thromboxane A2, were almost completely (greater than 90 percent) inhibited by low doses of aspirin. The urinary excretion of immunoreactive thromboxane B2 was significantly reduced without changes in the level of 6-keto-prostaglandin F1 alpha, a product of prostacyclin. Mass spectrometric analysis showed that aspirin reduced the excretion of the 2,3-dinor-thromboxane B2 metabolite--mainly of platelet origin--by 81 percent and of thromboxane B2, probably chiefly of renal origin, by 59 percent. The urinary excretion of 6-keto-prostaglandin F1 alpha and of its metabolite 2,3-dinor-6-keto-prostaglandin F1 alpha was not affected. Low doses of aspirin only partially (63 percent) reduced neonatal serum thromboxane B2. No hemorrhagic complications were observed in the newborns. Thus, in women at risk for pregnancy-induced hypertension, low doses of aspirin selectively suppressed maternal platelet thromboxane B2 while sparing vascular prostacyclin, but only partially suppressed neonatal platelet thromboxane B2, allowing hemostatic competence in the fetus and newborn.
有证据表明，低剂量阿司匹林可对妊娠高血压的病程产生有利影响，但其机制虽被认为与抑制血小板血栓素生成有关，但尚未明确。我们进行了一项随机研究，探讨长期每日服用60毫克阿司匹林（n = 17）或安慰剂（n = 16）对有妊娠高血压风险女性的血小板血栓素A2和血管前列环素的影响。低剂量阿司匹林与更长的孕期和新生儿体重增加相关。血栓素B2是血栓素A2的稳定产物，其血清水平几乎完全（超过90%）被低剂量阿司匹林抑制。免疫反应性血栓素B2的尿排泄显著减少，而前列环素产物6 - 酮 - 前列腺素F1α的水平无变化。质谱分析显示，阿司匹林使主要源于血小板的2,3 - 二去甲血栓素B2代谢产物的排泄减少81%，使可能主要源于肾脏的血栓素B2的排泄减少59%。6 - 酮 - 前列腺素F1α及其代谢产物2,3 - 二去甲 - 6 - 酮 - 前列腺素F1α的尿排泄未受影响。低剂量阿司匹林仅部分（63%）降低新生儿血清血栓素B2。新生儿未观察到出血并发症。因此，对于有妊娠高血压风险的女性，低剂量阿司匹林选择性抑制母体血小板血栓素B2，同时保留血管前列环素，但仅部分抑制新生儿血小板血栓素B2，使胎儿和新生儿具备止血能力。
