Novak Michael, Schlagenhauf Axel, Bernhard Heike, Schweintzger Sabrina, Leschnik Bettina, Muntean Wolfgang
Department of Pediatrics and Adolescent Medicine, Medical University of Graz, Graz, Austria.
Blood Coagul Fibrinolysis. 2011 Oct;22(7):588-92. doi: 10.1097/MBC.0b013e328349f190.
Neonates have lower levels of clotting factors as well as inhibitors. Effects of heparin in neonatal plasma differ from those in adult plasma, and dosage recommendations cannot be extrapolated from adult trials. Riveroxaban is an oral direct factor Xa inhibitor that can achieve an anticoagulant effect without dependence on anti-thrombin. We performed comparative thrombin generation measurements in neonatal cord and adult plasma with different concentrations of unfractionated heparin and rivaroxaban to evaluate the potential of rivaroxaban in neonatal anticoagulation. The impact of heparin or rivaroxaban on the neonatal and adult hemostatic system was determined measuring calibrated automated thrombin generation and activated partial thromboplastin time in platelet-poor plasma pools of 15 adult samples or 15 neonatal cord samples and addition of seven increasing concentrations of heparin or rivaroxaban, respectively, to the pooled samples. Lag time, time to peak and peak height of thrombin generation in neonatal cord samples were significantly less affected by different heparin concentrations than in adult samples, whereas the impact on reduction of endogenous thrombin potential was higher in neonatal cord samples. The impact of rivaroxaban on thrombin generation parameters showed better comparability between neonatal cord and adult samples. Both anticoagulants showed the same differences in activated partial thromboplastin time between adult and neonatal plasma at each concentration. Rivaroxaban shows a very similar pattern in neonatal cord and adult plasma in suppressing thrombin generation and prolonging activated partial thromboplastin time values, suggesting that dose finding may be easier with rivaroxaban in neonates.
新生儿的凝血因子及抑制剂水平较低。肝素在新生儿血浆中的作用与在成人血浆中的不同，不能从成人试验中推断出新生儿的用药剂量建议。利伐沙班是一种口服直接Xa因子抑制剂，可在不依赖抗凝血酶的情况下实现抗凝效果。我们用不同浓度的普通肝素和利伐沙班在新生儿脐带血和成人血浆中进行了凝血酶生成的比较测量，以评估利伐沙班在新生儿抗凝中的潜力。通过测量校准的自动凝血酶生成和活化部分凝血活酶时间，确定肝素或利伐沙班对新生儿和成人止血系统的影响，分别向15份成人样本或15份新生儿脐带血样本的贫血小板血浆池中添加七种浓度递增的肝素或利伐沙班。与成人样本相比，不同浓度的肝素对新生儿脐带血样本中凝血酶生成的延迟时间、达到峰值的时间和峰值高度的影响明显较小，而对新生儿脐带血样本中内源性凝血酶潜力降低的影响则更大。利伐沙班对凝血酶生成参数的影响在新生儿脐带血和成人样本之间显示出更好的可比性。在每个浓度下，两种抗凝剂在成人和新生儿血浆中的活化部分凝血活酶时间差异相同。利伐沙班在新生儿脐带血和成人血浆中抑制凝血酶生成和延长活化部分凝血活酶时间值的模式非常相似，这表明在新生儿中使用利伐沙班更容易确定剂量。
