Would you consider using transdermal estrogen in a patient with “high risk” APLS patient on warfarin?

Given her clinical diagnosis of high-risk APS, I would first trial nonhormonal therapies or progesterone-only therapies for management of her post-menopausal symptoms. Current ACR guidance recommends against hormone replacement therapy in patients with APS on anticoagulation (Sammaritano et al., PMID 32090480). However, if nonhormonal therapies were ineffective and the patient has been well controlled on warfarin (INRs within the target 2-3 range), transdermal estrogen does have the least thrombotic risk and thus would be reasonable to consider. Patient should be counseled that we don't have data specifically in high-risk APS patients receiving transdermal estrogen. It would be important to ensure INR is within range during her therapy with...

The ACR guidelines apply to 1) patients with a Rheumatic/Musculoskeletal disease (RMD) AND APS/+aPLs. This short case stem doesn't mention an RMD. 2) Not those on anticoagulation, so really can't be referenced here.

We also know that the route of estrogen delivery greatly impacts VTE risk and that transdermal is very low and does not increase VTE incidence. This came out after the guidelines were published for prospective. Sobel and Shen, PMID 35357370

Our hematology colleagues have looked into this more specific question of anticoagulation + estrogen in either contraception or HRT and have not found an increase in VTE incidence in this population. Hormonal Therapy Does Not Increase VTE Risk in Women on Anticoagulant Therapy. This could be ap...

I wouldn't categorically rule out its use, but I would be very frank with the patient about risks and benefits. While transdermal estrogen is felt to have a much better VTE risk profile than oral estrogen, there is still largely a sense that there is some risk. In a patient with multiple types of thrombosis (VTE + arterial) I would want to trial all non-hormonal options possible before trying estrogen.

That said, we have evidence that for patients on anticoagulation, adding hormonal therapy does not seem to increase thrombotic risk. The caviat here is that I do not know of a study like this where patients with APLS are well-represented, so this requires some extrapolation.

If they have not had further thromboses since starting on warfarin and...