Schmidt B, Buchanan M R, Ofosu F, Brooker L, Hirsh J, Andrew M
Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada.
Thromb Haemost. 1988 Oct 31;60(2):289-92.
The relative deficiency of antithrombin III (AT III) in neonatal plasma results in lower recovery of heparin in some assay systems. It is uncertain whether low AT III levels also limit the antithrombotic effects of heparin in this age group. We therefore compared the antithrombotic properties of heparin in mature pigs and newborn piglets, whose coagulation and inhibitor system closely resembles that of the human neonate. Animals were pretreated with saline, 10 or 25 U/kg heparin (n greater than or equal to 16 per age group and dose). Following an injection of 100 U/kg thrombin, systemic 125I-fibrinogen consumption and local 125I-fibrinogen incorporation into jugular venous stasis thrombi were measured. Significantly more 125I-fibrinogen was consumed in piglets than in pigs systemically (p less than 0.0001), as well as within the occluded vein segment (p = 0.0112), largely because heparin was less effective in piglets than in pigs. This neonatal resistance to heparin could not be explained by lower heparin levels in the newborn animals. However, pretreatment with AT III concentrate significantly improved the antithrombotic properties of heparin in this age group (p less than 0.0001). We conclude that physiologically low AT III levels reduce the efficacy of heparin in neutralizing thrombin activity in newborn piglets. We speculate that AT III deficiency may also limit the antithrombotic properties of heparin in newborn infants with thrombotic disease.
新生儿血浆中抗凝血酶III（AT III）相对缺乏，导致在某些检测系统中肝素的回收率较低。尚不确定低AT III水平是否也会限制该年龄组中肝素的抗血栓形成作用。因此，我们比较了成熟猪和新生仔猪中肝素的抗血栓形成特性，它们的凝血和抑制剂系统与人类新生儿的非常相似。动物分别用生理盐水、10或25 U/kg肝素预处理（每个年龄组和剂量n≥16）。注射100 U/kg凝血酶后，测量全身125I-纤维蛋白原的消耗以及局部125I-纤维蛋白原掺入颈静脉淤滞血栓的情况。与猪相比，仔猪全身（p<0.0001）以及闭塞静脉段内（p=0.0112）消耗的125I-纤维蛋白原明显更多，这主要是因为肝素在仔猪中的效果不如在猪中。新生动物中肝素水平较低并不能解释这种对肝素的新生儿抵抗。然而，用AT III浓缩物预处理可显著改善该年龄组中肝素的抗血栓形成特性（p<0.0001）。我们得出结论，生理性低AT III水平会降低肝素中和新生仔猪凝血酶活性的功效。我们推测，AT III缺乏也可能会限制患有血栓性疾病的新生儿中肝素的抗血栓形成特性。
