tPA for patients on DOAC

I went through this before when I had stroke patient with altered mentation, we were not able to tell if he was taking his Eliquis or not. So here is what I’ve gathered from that time.  

There are two situations for patient on DOACs coming with acute stroke:

1- If they are not able to tell if they take their medications, as in dementia or obtunded patients. We can test for Anti Factor Xa, if normal (0), it means they haven’t taken their DOACs. 

2019 guidelines states:“Alteplase could be considered when appropriate laboratory tests such as aPTT, INR, ecarin clotting time, thrombin time, or direct factor Xa activity assays are normal or when the patient has not taken a dose of these ACs for >48 h and renal function is normal.” –> So, factor Xa assay can be used to decide if they can get tPA.

2- if we know patient has been taking it and coming with severely disabling stroke. We can test factor Xa to tell if the medication is still working and their blood is still ‘thin’ (which precludes tPA) or not. This may be more relevant if the last dose was > 12h ago (half life for DOACs is around 12h). Since it is not a standard of care yet, will have to discuss it with family.

There are two types of Factor Xa assay, the general (heparin-calibrated) which is available in all hospitals and results are expressed in IU/ml, usually can be done within 10-15 minutes and the apixaban-calibrated or rivaroxaban-calibrated factor Xa with results expressed in ng/ml. Different studies showed that there is variation in DOACs trough levels. Here for example, rivaroxaban trough ranged from9.02‐147 ng/m. Levels < 30ng/ml is considered not clinically significant by many trials. Some trials as Annexa4, they didn’t give reversal agent Andexxa to patients with Anti-Xa levels <75 ng/ml presenting with major bleeding.

If DOAC-calibrated anti-Xa tests are not available, can we use the heparin-calibrated anti-Xa tests instead?

There has been multiple studies that compared the general Xa-assay (heparin calibrated) to DOAC-calibrated Xa and showed positive correlation. compared heparin and DOAC-calibrated Xa, using cut-off of <0.3 IU/ml ruled out relevant DOAC concentrations with sensitivity of 92%.​– Japanese guidelines implementing the same principle of testing for coagulation profile (table 4) and giving tPA accordingly.

So, bottom line, if a patient on DOAC presented with severe stroke, last dose of DOAC was >12h then we may test Xa assay (available within 15 minutes). Levels < 0.3 IU/ml may indicate absence of clinically significant concentration.