Baier Katrin, Cvirn Gerhard, Fritsch Peter, Köstenberger Martin, Gallistl Siegfried, Leschnik Bettina, Muntean Wolfgang
Ludwig Boltzmann Researrch Institute for Pediatric Hemostasis and Thrombosis, Medical University of Graz, Graz, Australia.
Pediatr Res. 2005 May;57(5 Pt 1):685-9. doi: 10.1203/01.PDR.0000156515.49293.F8. Epub 2005 Feb 17.
Neonatal plasma clots slower than adult plasma, and only 30-50% of peak adult thrombin activity can be produced in neonatal plasma when high amounts of tissue factor (TF) are added to trigger clotting, as used in standard clotting assays. Plasma activation by addition of low amounts of TF probably better reflects conditions in vivo. Under these conditions, cord plasma clots faster than adult plasma. In the present study, we show that after activation with low amounts of TF, higher amounts of the anticoagulants heparin and hirudin are required in cord plasma for effective inhibition of thrombin generation compared with adult plasma. After strong activation with high amounts of TF (30 microM), the thrombin potential was significantly more suppressed in cord plasma compared with adult plasma in the presence of 0.4 IE/mL heparin (-92 versus -75%; p < 0.01) and in the presence of 2 IE/mL hirudin (-18 versus -8%; p < 0.01). In contrast, after weak activation with low amounts of TF (30 pM), the thrombin potential was significantly more suppressed in adult plasma compared with neonatal plasma in the presence of 0.025 IE/mL heparin (-93 versus -8%; p < 0.01) and in the presence of 2 IE/mL hirudin (-89 versus -48%; p < 0.01). Our results show that in neonates, effects of anticoagulants very much depend on the type of activation used to initiate clotting, and doses of anticoagulants should not be derived from studies done in adults, because potentially higher doses of anticoagulants may be required.
新生儿血浆的凝结速度比成人血浆慢，在标准凝血试验中，当添加大量组织因子（TF）以触发凝血时，新生儿血浆中只能产生30%-50%的成人凝血酶峰值活性。添加少量TF激活血浆可能更能反映体内情况。在这些条件下，脐带血浆的凝结速度比成人血浆快。在本研究中，我们发现，与成人血浆相比，用少量TF激活后，脐带血浆中需要更高剂量的抗凝剂肝素和水蛭素才能有效抑制凝血酶的生成。在用大量TF（30微摩尔）强力激活后，在存在0.4国际单位/毫升肝素的情况下（-92%对-75%；p<0.01）以及在存在2国际单位/毫升水蛭素的情况下（-18%对-8%；p<0.01），脐带血浆中的凝血酶潜力比成人血浆受到的抑制明显更大。相比之下，在用少量TF（30皮摩尔）弱激活后，在存在0.025国际单位/毫升肝素的情况下（-93%对-8%；p<0.01）以及在存在2国际单位/毫升水蛭素的情况下（-89%对-48%；p<0.01），成人血浆中的凝血酶潜力比新生儿血浆受到的抑制明显更大。我们的结果表明，在新生儿中，抗凝剂的效果很大程度上取决于用于启动凝血的激活类型，并且抗凝剂的剂量不应从在成人中进行的研究得出，因为可能需要更高剂量的抗凝剂。
