Non-criteria APS

The path to diagnosing a disease is usually a straightforward one. If the patient complains of symptoms, then either a blood test and/or scans confirm the diagnosis. APS is slightly different.

Historically, APS has been diagnosed on the basis of clinical and laboratory CRITERIA. These criteria were published in important papers that defined the disease (the Sapporo and Sydney criteria). The clinical criteria are either blood clots or certain types of pregnancy loss, and the laboratory criteria are three APS blood tests (please see below).

The standard definition of APS has been that a person with the disease must have at least one of the clinical criteria and one of the laboratory criteria.

APS blood tests

If your doctor suspects you may have APS, they should order the following three blood tests that look for antiphospholipid antibodies (aPL) in your blood:

• The anticardiolipin (aCL)
• The confusingly named lupus anticoagulant (LA)
• The anti-beta2-glycoprotein-1 (anti-B2GP1)

The first two tests have been used since the discovery of the condition, but the anti-B2GP1 test is more recent and may not be carried out in all hospitals.

If any of the above tests are positive and indicate you have aPL in your blood, then you will be asked to repeat the blood tests within six to twelve weeks to confirm that you are positive.

What is non-criteria APS?

In recent years there has been recognition that some people may have APS without fulfilling the criteria exactly. In particular, the possibility has been proposed that there are people with APS who persistently test negative in all three of the standard blood tests. So they fulfil the clinical criteria but not the laboratory criteria. This scenario is called seronegative APS.

There may be other people who test positive in one or more of the blood tests and have some symptoms very suggestive of APS – for example, migraine, heart valve problems and some types of rash - but they have not had clots or miscarriages. These patients fulfil the laboratory criteria but do not fulfil the clinical criteria exactly.

Patients like this – who fulfil one set of criteria but not the other – are sometimes said to have “non-criteria APS”.

It is important to be aware that the idea of non-criteria APS is still being developed, and only a very small minority of patients with APS are likely to have non-criteria APS. Currently, non-criteria APS is more a research concept than one used in clinical management.

Seronegative APS

In other autoimmune conditions, such as rheumatoid arthritis and lupus, seronegativity is an accepted diagnosis and patients can be treated accordingly. This has been a contentious issue where APS is concerned because the criteria say that all patients must be seropositive. However, there have now been many publications describing patients thought to have seronegative APS and there are two main possibilities:

1. The diagnosis of APS is wrong and the patient has a different condition.
    
2. The current laboratory tests are not sensitive enough and fail to identify the antibodies in all patients. This concept is supported by the more recent introduction of the anti-B2GP1, which yielded positive tests in patients who repeatedly had negative aCL and LA tests results. Research is still taking place to refine the aPL tests so even more accurate ones may be available in the future.

Confirming a diagnosis of seronegative APS (SN-APS) can be difficult as it is not officially recognised by many specialists. However, thanks to a piece of research undertaken by University College London (UCL) and St Thomas’ Hospital, which was driven by APS Support UK’s patient group, SN-APS is now becoming more accepted in the medical community.

The collaborative research project used a new laboratory test devised by Professor Rahman’s team at UCL and found that 10% of patients who had previously had clear clinical symptoms of APS but always tested negative did actually test positive for this new test. Please click here to read the abstract of the study that was published in the Annals of the Rheumatic Diseases in 2014.

What does this mean for patients?

If a person has a blood clot and tests show that they have APS, then treatment with anti-clotting drugs such as warfarin will be continued for much longer than if they do not have APS. Similarly, if a woman with APS becomes pregnant, the management of subsequent pregnancies will be different than if she did not have APS.

So there may be a very small group of patients in whom doctors diagnose “non-criteria APS” and therefore manage them as APS patients even though they do not fulfil the usual conditions necessary to diagnose this disease (for example, they are seronegative). If this is the case for you, then your doctor should explain it to you and also document it in letters sent to your GP.