Summary
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 he-parinoids but can be also be used
to monitor their reversal.
Keywords
Thrombin generation - APTT - anti-Xa assay - heparinoids - reversal agents