Episode 079: Heme Consult Series: When anticoagulation fails, Part 1
It’s time for another Heme Consult series, this time focusing on another common question we see in the hospital and in clinic: “is this anticoagulation failure?”
In this two-part series, we break down how we approach the workup to determine exactly this. In this first episode, we discuss “DOAC failure.”
How do we approach a patient with a potential “DOAC failure”?
When a patient develops recurrent thrombosis on DOAC therapy, the first step in their evaluation is to assess for true DOAC failure versus inadequate anticoagulation.
Step 1: Get a detailed adherence history.
DOAC medications are reversible inhibitors which really work when taken very regularly and absorption is optimal.
Gather information about missed doses, irregular refills, medication organization, polypharmacy etc.
Assess for optimal absorption- e.g., Rivaroxaban needs fat for adequate absorption at therapeutic doses. Ask for detailed dietary history in relation to medication intake. Also exclude malabsorptive conditions like IBD, Celiac disease, bowel resections, etc.
Step 2: Perform anticoagulation assay.
Check for detectable levels of anti-coagulation with an assay.
Binary results: present or absent; does not give you therapeutic range.
Same test, different names in different labs: Heparin level/LMWH level/apixaban level/ rivaroxaban level/ Anti-XA level
Does not work for Dabigatran (thrombin inhibitor)
Step 3: Look for anatomic causes for thrombosis.
Rule out extrinsic compression from a tumor, malignant invasion of blood vessel
Review prior imaging and compare old vs new clot.
If anatomic reason is found, continue same AC and discuss with IR/surgery about fixing the anatomic issue.
Step 4: Compare old and new imaging to confirm presence of “new” clot.
The old clot may not go away completely, since AC are not clot busters, only help restore blood flow around the clot, or with collaterals.
Old residual clot becomes organized and/or scar tissue.
Once you have determined that the patient has undetectable levels of AC, regular adherence, and no anatomic reason for recurrent thrombosis, you are concerned about “true DOAC failure”.
Next steps:
No benefit of switching from one DOAC to another (unless severe side effect leading to non-adherence or cost issue) for true DOAC failure
No benefit for increasing the dose, since there are no well-established therapeutic ranges.
Generally, opt for Warfarin or Enoxaparin.
A few reasons why Warfarin would be the preferred option in case of true DOAC failure:
Different mechanism of action. Acts on larger range of clotting factors, while DOACs target only activated Factor X or II.
Longer half-line with warfarin. Consistency of suppression of factor production is much more prolonged and durable (less fluctuations) with warfarin. DOACs remain active only while they are still circulating in blood stream.
Monitorability of therapeutic AC with INR is an option with warfarin.
Warfarin is immediately and fully reversible.
Another option is to use heparin products or fondaparinux. They work through irreversible inhibition of activated factor X (and sometimes II) via enzymatic digestion with antithrombin III.
Specific scenarios where you would consider treatment with warfarin (and not DOAC) upfront:
Antiphospholipid antibody syndrome with arterial manifestations like MI or CVA
“High-risk” APLS like triple positive disease
LV thrombus (although some data suggests that DOAC work just fine for this)
Mechanical heart valves
LVAD
The crew behind the magic:
Show outline: Dan Hausrath
Production and hosts: Ronak Mistry, Vivek Patel, Dan Hausrath
Editing: Resonate Recordings
Shownotes: Agrima Mian
Social media management: Ronak Mistry
We are proud to partner with HemOnc.org!
Want to learn more about the trials that lead to the regimens discussed today? What about dosing schedules? See links in the show notes for a link to HemOnc.org
