Thrombin generation assays are superior to traditional tests in assessing anticoagulation reversal in vitro

Abstract

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.

Reliable low-molecular-weight heparin reversal in a child undergoing emergency surgery: a case report

“…Therefore, because of the high risk of both venous and arterial thrombosis, rFVIIa should be reserved for patients with a contraindication to protamine or LMWH-related bleeding refractory to protamine. In another clinical study, PCC and aPCC have been used but did not show any improvement in the anti-Xa or anti-IIa activity in plasma exposed to enoxaparin [15] and, therefore, are not recommended for the reversal of LMWH.…”

Thrombin generation assays and their clinical application

“…A TG a VKA-terápia kezdeti szakaszában az alacsony molekulatömegű heparinnal történő együttes alkalmazás során is alkalmas az antikoaguláció monitorozására [30]. A TG nemcsak a heparin- [31] és alacsony molekulatömegű heparin- [32] terápia monitorozására alkalmas, hanem a heparinhatás közömbösítésé-re alkalmazott készítmények hatásának az ellenőrzésére is [33]. Az új típusú orális antikoaguláns szerek [34], azaz a direkt és reverzíbilis alvadási faktor inhibitorok antikoagulációs hatása is jellemezhető a TG-paraméterek alapján [35].…”

Alte und neue Gerinnungshemmer

“…Sie hemmen indirekt -durch Erhöhung der Antithrombin-(AT-)Aktivität -die Faktoren IIa und Xa. Hierbei zielen die LMWH mehr auf Faktor Xa, hemmen aber auch, abhängig von [13,14].…”