Got a Clot? When to Suspect Antiphospholipid Syndrome

This transcript has been edited for clarity.

Matthew F. Watto, MD: Welcome to The Curbsiders. I'm Dr Matthew Frank Watto, here with America's primary care physician, Dr Paul Nelson Williams. Today's topic is antiphospholipid syndrome (APLS).

I've wanted to do this topic for a long time. We often come across antiphospholipid antibodies because they can be present even in patients who don't have the syndrome. When we test for antiphospholipid antibodies, we sometimes find them in patients who aren't having clotting. People can develop these antibodies, but it's hard to predict which patients with these antibodies are going to develop a clot. That's because they not only must have the antibodies, but the antibodies must be able to activate the clotting cascade. We don't have testing yet to predict who can do that until they have an event.

So, when should we suspect APLS and send the testing?

Paul N. Williams, MD: I often see these ambiguously positive tests when the APLS is part of an order set. It comes back positive, and then I think, What do I do with this? Rather than doing that, Dr Arielle Langer suggests that we do more directed testing on patients in whom we should have high suspicion for APLS. That includes patients who have arterial clotting without atherosclerosis (eg, younger patients in whom that kind of clotting would be unusual), or patients with clotting despite appropriate anticoagulation therapy. If they are overcoming anticoagulation for reasons that are unclear, that's when to think about APLS.

An important sign that is often missed is venous clotting at unusual sites, such as splanchnic and intracerebral clotting. These events should also prompt suspicion for APLS. A history of autoimmunity is the risk factor we classically think about (but not just lupus), and someone with a clot should prompt testing as well.

Watto: New criteria were released in 2023, but they are very research heavy. Our expert recommended continuing to use the revised Sapporo criteria, which basically require a clinical component — either arterial or venous clotting, plus at least one of the antibodies: lupus anticoagulant, beta-2 glycoprotein, or anticardiolipin. If the patient has at least one of those three and a clot, you should test them again 12 weeks later. The reason is that inflammation in the body can cause transient positivity (false positives) on some of these tests. They have to remain positive at 12 weeks for you to make the diagnosis. You want to see the titers of the antibodies above 40. Between 20 and 40 is an ambiguous range. Ideally, you should test for lupus anticoagulant before starting any kind of blood thinner, because once they are on a blood thinner it becomes more difficult to interpret the test.

Williams: It's a rare occasion when you would stop anticoagulation solely for the purpose of checking that level after the fact. Once that river's been crossed, you're kind of stuck there.

Watto: What about the treatment for APLS? Can we use direct oral anticoagulants (DOACs)?

Williams: The first-line treatment is warfarin. It's old-school. People are becoming increasingly terrified of warfarin as they become less familiar with it. The INR goal is between 2 and 3. We just don't have a lot of data on this, so Dr Langer aims for 2-3 because benefits haven't been seen at higher INR goals. With DOACs, recurrent clots were seen compared with warfarin in a couple of studies, regardless of whether the patient has so-called single, double, or triple antibody positivity. We should prescribe warfarin unless the patient is very low risk and absolutely doesn't want to be on warfarin. Then you can consider a DOAC, but for most patients it's going to be warfarin.

Watto: Patients who have APLS are at high risk for clotting and should be bridged when they're going for surgical procedures. Dr Langer made the point that we should involve the patient's hematologist if they're going for a surgical procedure to make sure it's done correctly. Often when we try to bridge somebody, it doesn't go smoothly. This is one time when you need it to go smoothly because these patients are really at high risk.

Williams: Even if you do it perfectly, hematology is going to be lightly annoyed at you if they're not involved in the decision-making process, so just give your friendly neighborhood hematologist a call.

Watto: This was an extensive episode. We also talked about obstetric APLS. If you're interested in hearing more, please click on this link.