Episode 080: Heme Consult Series: When anticoagulation fails, Part 2
We started this conversation last week! This week, we focus on how to approach warfarin and enoxaparin failure! Be sure to check out Episode 079 for part 1!
How do we approach a patient with a true “Warfarin failure”?
Used the same steps as mentioned above first to confirm that this is indeed a new thrombus, while patient being adequately anticoagulated with warfarin (INRs therapeutic). Next steps:
We need to determine if the patient’s INR level correspond to a therapeutic level of factor X suppression. E.g., in the case of APLS, the patient’s lupus anticoagulant antibody may be interfering with the PT assay.
Earlier, recommendation would be to empirically increase the “goal INR range”, but now we can directly measure the degree of factor X suppression.
One method is to use chromogenic assay of factor X activity. This test determines what percent of normal factor X activity is present in the patient’s plasma sample by comparing the degree of color change to a standard curve (after adding substrate for activated factor X).
“Therapeutic range” on this assay for warfarin therapy is 20%- 40% of normal, which corresponds to an INR of 2-3, if PT/INR assay is functioning normally.
So, for e.g., If patient is having recurrent thrombosis at INR of 2.7, and chromogenic factor X came back at 48%, the therapeutic INR range could be increased to 3-4. Once that is achieved, the chromogenic factor X levels should normalize (20%-40%).
If recurrent clotting events while on therapeutically suppressed Xa level, then try to push them towards lower end of normal range (~20%) or switch to injectable anticoagulant.
How do we approach a patient with a true “Enoxaparin failure”?
Confirm that the patient is not underdosed for their body weight, given that therapeutic dose is 1mg/kg. Since these medications come in standard sizes, make sure the actual dose delivered to the patient is not much lower than 1mg/kg.
No firmly established ranges for enoxaparin drug level but typically aim for drug level between 0.5-1.0. Level should be drawn 4-6 hours after last dose, and patient should have received at least 3 shots of enoxaparin at that dose.
If level is below therapeutic threshold, can increase enoxaparin dose, and re-draw levels after 3 shots have been given at the new dose.
If level is within therapeutic range, and there is no alternate anatomic explanation for recurrent thrombosis, then you can try targeting upper limit of the therapeutic range.
How to manage a patient with multiple breakthrough thrombotic events while on therapeutic anticoagulation?
If there are multiple breakthrough events while on therapeutic anticoagulation, especially when in rapid succession, patient will need to be admitted for IV anticoagulation.
Exclude new diagnosis that could lead to a “thrombotic storm”.
Make sure they don’t have an indication for additional therapies like antibody eradication or complement inhibition.
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
