Blood tests for antiphospholipid antibodies

There are three main blood tests used to diagnose APS and they are all looking for antiphospholipid antibodies (aPL):

• Anticardiolipin antibodies (aCL)
• Lupus anticoagulant (LA)
• Anti-beta2-glycoprotein-1 (anti-B2GP1)

The result of the blood clotting lupus anticoagulant test is either negative or positive, while the results of the other two specific antibody tests are given in figures.

The reason for the three tests is that they measure aPL in different ways and many patients are positive for just one test, although some can be triple positive. So this means that one test alone could miss the diagnosis. The most common test to come back positive is the aCL, then the LA and finally the anti-B2GP1. People who have more than one positive test are considered at higher risk.

It is usually advisable to repeat the blood tests as one positive test for aPL does not necessarily mean that a person has APS. This is because harmless aPL can be detected in the blood for brief periods in association with a wide variety of infections such as chickenpox, and certain drugs including antibiotics and some blood pressure tablets. For this reason, the tests should be repeated typically after 12 weeks. If someone has only one positive test and it quickly becomes negative again, then it is unlikely they have APS.

Anticardiolipin antibodies – aCL

In this test, the chemical known as anticardiolipin is coated on a glass or plastic surface and the test serum is added. The stronger the binding of the blood serum, the higher the level of aCL.

Nationally, laboratories differ in the way they carry out their tests so it is impossible to compare results but, for an example, the ranges given out by St Thomas’ Hospital in London are:

aCL 0-15 - normal
aCL 15-40 - medium
aCL >40 - high

Many laboratories also record the particular class of the antibody (IgG or IgM) which is doing the binding, IgG being more likely (though not uniquely) to cause thrombosis. Again, laboratory ranges will differ all over the country but at St Thomas’ Hospital the ranges given out are:

IgG Range GPL

<2 Negative
2.0-20.0 Low Positive
20.0-80.0 Moderate
>80 High

IgM Range MPL

<3.2 Negative
3.2-6.0 Low Positive
6.0-50.0 Moderate
>50.0 High

The higher the titre (number) is, the more aPL a person has in their blood which suggests they are at greater risk of blood clots and other symptoms.

If a patient is already taking anticoagulants including aspirin, heparin, rivaroxaban or warfarin, it is still possible to take the aCL test as the results will not be affected.

The aCL test is not perfect which is why it is also necessary to perform the other two tests – the LA and the anti-B2GP1.

Lupus Anticoagulant – LA

This inaccurate and confusing name is given to the second test for APS. Lupus anticoagulant is in fact a double misnomer and is NOT a test for lupus and is not an anticoagulant. Unsurprisingly, many people assume they have lupus when they are told they have tested positive for the LA but this is not true – they are testing positive for the aPL associated with APS.

The lupus anticoagulant got its name because it was first discovered in patients with lupus and it interfered with a laboratory clotting test, making it look as though the patient was taking an anticoagulant. We now know that most lupus patients do not test positive for the lupus anticoagulant and that the LA causes clotting and is not an anticoagulant after all. However, the name seems to be fixed in laboratory terminology and would be difficult to change now.

Patients who are already taking warfarin are unable to take the LA test as warfarin interferes with the results. It can take approximately ten days for the effects of warfarin to wear off, but an alternative such as heparin can also affect the interpretation of the LA results so it is important to discuss this with a specialist before a patient proceeds.

The LA test is somewhat imperfect, being positive in about 50% of APS patients. Nonetheless, it can be positive in the face of a negative aCL test and is, therefore, widely used.

Anti-beta2-glycoprotein-1

The science behind the thrombotic tendency in APS is always improving and moving on – thanks to the ongoing research around the world.

It was soon discovered that for aPL to do their worst, binding to a protein was required. One such protein was called anti-beta2-glycoprotein-1. Some laboratories now include an assay for anti-B2GP1 for completeness and extra precision when testing, and it is usually tested on patients who have obvious symptoms of APS but have consistently negative aCL and LA test results.

The anti-B2GP1 can be tested if a patient is already taking anticoagulants such as warfarin, heparin, rivaroxaban or aspirin but, due to the complexity of the test, it is not yet widely available in all hospitals and laboratories.