November 2020

UPDATE ON DOAC STOP

A doctors’ “quip” online recently was “It usually requires a considerable time to determine with certainty the virtues of a new method of treatment and usually still longer to ascertain the harmful effects.” (Dr Alfred Blalock).

If you substitute “testing” for “treatment” then this statement also rings true for pathology, perhaps that may change soon if the following articles have anything to do with it:

New publications referring to DOAC Stop:

1. "Direct oral anticoagulant adsorption: Impact on lupus anticoagulant testing - Review of the literature and evaluation on spiked and patient samples". De Kesel PM, Devreese KMJ. J Thromb. Haemostas. 2020; 18: 2003-17.

This is a thorough review and investigation into the practical use of DOAC Stop in lupus anticoagulant (LAC) testing on 152 patient samples and various other DOAC-spiked plasmas. Quoting selectively from this paper- "In the majority of samples DOAC Stop eliminated false LAC results caused by DOAC, as observed in 7 other studies. DOAC adsorption with DOAC Stop represents a straightforward procedure to deplete samples of DOAC even at supratherapeutic levels…" Apixaban was reduced but not completely removed in a couple of plasmas. There were some minor changes in clotting times close to cutoff values among VKA and non-DOAC plasmas leading to altered diagnosis of LAC.
The final recommendation was that DOAC Stop can be used safely for LAC testing on plasmas from patients on DOACs. It is interesting that it does not recommend DOAC Stop for LA testing on plasmas that are not known to contain DOACs. Could it be that some of these cases had false positive LA due to DOACs in the first place?

2. Another paper from the same eminent laboratory is "Interference of DOAC Stop and DOAC Remove in thrombin generation and coagulation assays". Monteyne T, De Kesel P, Devreese KMJ. Thromb. Res. 2020; 192: 96-99.

This paper concludes that the influence of these agents is "minimal" in normal plasmas and that they can be safely used "to avoid DOAC influence on coagulation tests".
While the title of this "letter to the editor" is slightly misleading, it provides quite interesting results on the effect of these 2 DOAC adsorbing agents on thrombin generation assays (TGA). Also it reports no significant effects on PT, protein C or antithrombin assays, but small reductions in fibrinogen and free protein S tests.
It confirms that both adsorbents reduce tissue factor pathway inhibitor (TFPI) by approximately 15%, leading to a small procoagulant effect in various parameters of the TGA if this is carried out using dilute tissue factor. However, the effects were less than normal variations in the TGA and are stated to be "not clinically relevant". (Note that TFPI is not known to affect conventional clotting assays).
It is claimed that both agents prolonged APTT tests slightly, but a close look at their results shows no such effect with DOAC Stop. Indeed, there was a small shortening of 0.3%, whereas DOAC Remove caused a prolongation of 1.5% in APTT. These are minor changes which are not statistically significant. In almost every other test in this study, DOAC Stop caused slightly less interference than DOAC Remove.

3. The ISTH subcommittee on lupus anticoagulant testing has also issued new guidelines "Lupus anticoagulant detection in anticoagulated patients. Guidance from the scientific and standardization committee for lupus anticoagulant/antiphospholipid antibodies of the ISTH". Tripodi A, Cohen H, Devreese KMJ. J. Thromb. Haemost. 2020; 18: 1569-1575.

This article reviews the problems of testing for LAC in patients on warfarin or DOACs. Mixing tests usually help with warfarin plasmas but not for DOACs. Discontinuation of treatment obviously does work but puts patients at risk. Towards the end of this article, DOAC Stop and DOAC Remove are mentioned and it is suggested that the use of appropriate DOAC absorbents "is promising".

4. "Comprehensive review of the impact of direct oral anticoagulants on thrombophilia diagnostic tests: Practical recommendations for the laboratory". Siriez R, DogneJ-M, Gosselin R, et al. Int J Lab Hematol. 2020; online ahead of print.

It's pretty obvious that thrombophilia test results from patients on DOACs should be interpreted with caution. This paper elaborates on these problems and then briefly mentions that compounds or devices removing DOACs (such as DOAC Stop) and the use of methods insensitive to DOACs should be considered. It seems that my own review on this topic published in the same journal previously may not have been adequate. (Exner T, Rigano J, Favaloro EJ."The effect of DOACs on laboratory tests and their removal by activated carbon to limit interference in functional assays Int J Lab Hematol 2020; 420(Suppl. 1): 41-48).


A practical hint:

Some labs report difficulty in separating DOAC Stop completely from treated plasmas with residual particles in the supernatant plasma. We recommend the use of longer tubes for centrifuging. Microfuge tubes with a cone tip are also better at keeping supernatant plasma separate from the sedimented activated carbon pellet. However, we have found that small amounts of residual DOAC Stop in plasmas do not affect clotting time results. AC can also be filtered out provided that the filter itself does not affect clotting time results.

If you are interested in DOAC-Stop or any of our products we would like to hear from you. Haematex is the only Australian distributor which carries out local R&D into coagulation diagnostics.

When you purchase diagnostics from us, part of the money goes towards projects such as our own locally made DOAC-Stop, Inhibitor Dots, research on dRVVT and lupus anticoagulants.

Thanks for reading, we are grateful that we can act as your local coag news resource.