Gatt Alex, van Veen Joost J, Woolley Anita M, Kitchen Steve, Cooper Peter, Makris Michael
Sheffield Haemophilia and Thrombosis Centre, Royal Hallamshire Hospital, Sheffield, UK.
Thromb Haemost. 2008 Aug;100(2):350-5.
Even though new anticoagulants are being devised with the notion that they do not require regular monitoring, when bleeding occurs, it is important to have an antidote and a reliable test to confirm whether the anticoagulant effects are persisting. We examined the effects of five heparinoids, unfractionated heparin (UFH), tinzaparin, enoxaparin, danaparoid and fondaparinux on the traditional APTT and anti-Xa assays as well as on the calibrated automated thrombogram (CAT). We also studied the ability of protamine sulphate (PS), NovoSeven, FEIBA and FFP to reverse maximum anticoagulation induced by the different heparinoids. The CAT was the only test to detect the coagulopathy of all the anticoagulants. PS produced complete reversal of UFH, and this could be monitored with all three tests. Tinzaparin can also be completely neutralised in vitro with high doses of PS, but the maximum enoxaparin reversal achieved with PS is only approximately 60%. Fondaparinux does not significantly affect the APTT and PS has no significant effect on its reversal. Only NovoSeven was able to correct the fondaparinux induced CAT abnormalities whilst having no effect on the anti-Xa level. None of the reversal agents was very effective in danaparoid spiked plasma but NovoSeven, at high dose, increased the ETP by 40% and reduced the anti-Xa level from 0.93 to 0.78 IU/ml. We conclude that the CAT is superior to the traditional coagulation tests in that it not only detects the coagulopathy of all the heparinoids but can be also be used to monitor their reversal.
尽管新型抗凝剂的设计理念是无需定期监测，但出血发生时，拥有解毒剂和可靠的检测方法以确认抗凝效果是否持续存在非常重要。我们研究了五种类肝素（普通肝素（UFH）、替扎肝素、依诺肝素、达那肝素和磺达肝癸钠）对传统活化部分凝血活酶时间（APTT）和抗Xa检测以及校准自动血栓图（CAT）的影响。我们还研究了硫酸鱼精蛋白（PS）、诺其、活化凝血酶原复合物（FEIBA）和新鲜冰冻血浆（FFP）逆转不同类肝素诱导的最大抗凝作用的能力。CAT是唯一能检测所有抗凝剂引起的凝血病的检测方法。PS能完全逆转UFH的抗凝作用，且这一过程可用所有三种检测方法进行监测。替扎肝素在体外也可用高剂量PS完全中和，但PS对依诺肝素的最大逆转率仅约为60%。磺达肝癸钠对APTT无显著影响，PS对其逆转也无显著作用。只有诺其能够纠正磺达肝癸钠诱导的CAT异常，同时对抗Xa水平无影响。在达那肝素加样血浆中，没有一种逆转剂非常有效，但高剂量的诺其使内源性凝血酶原时间（ETP）增加了40%，并使抗Xa水平从0.93降至0.78 IU/ml。我们得出结论，CAT优于传统凝血检测方法，因为它不仅能检测所有类肝素引起的凝血病，还可用于监测它们的逆转情况。
