APS 101 takes you through the ins and outs of APS, providing facts and key information to help you better understand the disease.
APS 101 is written by Jacqueline Madison, MD, Assistant Professor in the Division of Rheumatology and member of the APS Research Labs. In this month’s edition, Dr. Madison discusses the oddly named “lupus anticoagulant” lab test - the history behind the name, and the questions the test answers.
Lupus Anticoagulant Lab Test
Patients have asked me: “I have a positive lupus anticoagulant, so does that mean I have lupus!?”
The short answer is no. A positive lupus anticoagulant does not necessarily mean that you have lupus. The long answer is, well, a bit longer!
First of all, what is this test? The lupus anticoagulant is one of the three most important ways that we test for antiphospholipid antibodies. It does not test for a specific antibody, but instead looks for their presence in an indirect way.
Anticoagulant
A basic definition: “anticoagulant.” If we break it down, we see it ends with “coagulant” meaning forming blood clots or stopping bleeding. “Anti-” implies the opposite, so putting that together, you might think this is a test for something that stops blood clots or thins the blood. In a way, it is, but the interpretation is more complex (and confusing).
History
Let’s go into the history of this test! In the 1950s, scientists and physicians noticed something unusual about the blood of patients with lupus. If they studied their plasma (the liquid part of blood) in a test tube, it took longer than usual for the plasma to clot. So, there was something in the lupus patients’ bloodstream that was working against normal clotting. Basically, it looked to researchers like there was an inhibitor of blood clotting (an anticoagulant) in the lupus blood.
In the 1960s, another group of scientists began to put the whole story together. We might have predicted that these lupus patients would be at risk for bleeding complications. BUT, the scientists reported that even though there was what looked like an anticoagulant in the test tube, there was an opposite-than-expected effect in the body: these patients actually had MORE blood clots! Not less!
Test Logistics
Fast forward to today. We do the test slightly differently, but with the same general approach - and with a better understanding of what we are looking for. This is not a simple yes-or-no test, but requires multiple steps and teamwork with our colleagues who are in the lab doing the testing.
First, the lab looks for that original finding from the 1950s: in certain clotting tests (that depend on phospholipids), does it take longer than normal for plasma to clot? As mentioned above, plasma is the liquid part of blood after all the cells have been removed. The phospholipids are important because they serve as a surface for all the clotting factors to find each other without cells. So, if it takes too long to clot, then either the phospholipids aren’t able to do their job, or something that normally forms the clot is missing.
Second, does the clotting still take too long even when mixed with normal plasma? This second part makes sure that there’s something preventing the clotting from working correctly (an inhibitor!). If the problem were instead a clotting protein deficiency (as happens in hemophilia), then the normal plasma would provide enough clotting proteins to return things to normal. This step confirms that there is an inhibitor present. It turns out that an antiphospholipid antibody is the type of inhibitor that we are testing for.
Third, the final step in our current test is to add a huge amount of extra phospholipids and make sure the clotting time goes back to normal. This final step tells us that the inhibitor is working specifically against phospholipids (which, in huge quantities, can soak up the inhibitor and prevent its effects) and not something else.
In summary, these antiphospholipid antibodies do one thing in the test tube (when all the cells have been removed from the blood), but a different thing in the person when cells are present. Put another way, in the test tube, it first looks like the antibodies are an “anticoagulant” but in people they work as a PRO-coagulant, promoting the formation of blood clots.
Lupus
Okay, so the anticoagulant testing part mostly makes sense, although it’s okay if you still find it a bit confusing. A lot of doctors find it tricky, too! What about that “lupus” part?
Well, because this abnormal blood clotting test was first studied in lupus patients, that is how the test was named. This name is a bit unfortunate because we now know that while some (perhaps half) of APS patients have another autoimmune disease like lupus, the other half do not. It is also puzzling to lupus patients who are negative for this test! Fortunately, there are much better and more definitive tests for a diagnosis of lupus that we can discuss another day.
Wrap Up
Here's a final note for our doctor friends. Interpreting the lupus anticoagulant test requires some extra caution in certain situations. Most important is that with some types of blood thinners, especially heparin products (like Lovenox) or direct oral anticoagulants (like Eliquis), we can’t tell how well the plasma naturally forms clots because the medications are present. Fortunately, if the patient is on Coumadin or warfarin, then an experienced lab may still be able to interpret the test results.
In summary, the lupus anticoagulant was first identified in mysterious lupus patients with seemingly thin plasma in the test tube that somehow still formed clots in their bodies. And despite the confusion it causes now, the name stuck. Aw shucks.
References:
Frick PG. Acquired circulating anticoagulants in systemic collagen disease; auto-immune thromboplastin deficiency. Blood. 1955 Jul;10(7):691-706. PMID: 14389382.
Bowie EJ, Thompson JH Jr, Pascuzzi CA, Owen CA Jr. Thrombosis in systemic lupus erythematosus despite circulating anticoagulants. J Lab Clin Med. 1963 Sep;62:416-30. PMID: 14061973.
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