Graham Hughes1 and Shirish Sangle2
(1)
The London Lupus Centre, London Bridge Hospital, London, UK
(2)
Louise Coote Lupus Unit, St Thomas’ Hospital, London, UK
Abstract
The central pillar in the diagnosis of APS is the detection of antibodies against phospholipids. Two tests are routinely used, the anticardiolipin test (aCL) and the so-called lupus anticoagulant (LA).
20.1 Introduction
The central pillar in the diagnosis of APS is the detection of antibodies against phospholipids. Two tests are routinely used, the anticardiolipin test (aCL) and the so-called lupus anticoagulant (LA).
Unfortunately, as some patients may have only one of the two tests positive, it is recommended that both tests are ordered.
20.2 Anticardiolipin Antibodies
Based on an old test for syphilis, the so-called Wasserman reaction (WR), the immunoassay for anticardiolipin (aCL), is far more sensitive and has become the most reliable and widely used test. The antibody is tested for ELISA in most labs. Unfortunately, as different ELISA kits use different recipes, there is variation from lab to lab.
Most labs measure the different classes of antibody – i.e., IgG aCL, lgM aCL and (though by no means routinely) IgA aCL.
Positive results are usually expressed as low, medium or high.
In general, a high IgG anticardiolipin result is more of a risk factor for thrombosis than IgM, but there are many exceptions to this rule.
Positive aCL tests are reasonably specific for Hughes Syndrome, and unlike, say, anti-DNA tests in lupus, tend to remain fairly constant.
20.3 Lupus Anticoagulant (LA)
This capricious test should have been abandoned long ago. It survives partly because in some cases of APS, the only positive test is the LA. It is a rather complicated test, which indirectly measures the effects of antiphospholipid antibodies on blood clotting. To make matters worse, there are a number of different ways to measure LA, such as the direct Russel Viper Venom Time (DRVVT).
The test is also affected by treatment and cannot be interpreted if the patient is taking Warfarin. And the name is unfortunate – it is neither a “lupus” test nor an “anticoagulant” test. However, until something better comes along, the name has stuck.
20.4 Anti-Beta 2 GP1
It is now recognised that antiphospholipid antibodies don’t in fact react solely with phospholipids.
[Realistically the name APS is wrong.] They react with a complex mix of phospholipid and “carrier” proteins. A number of these carrier proteins or “co-factors” are known, the most well recognised being Beta 2 GP 1 and prothrombin.
Anti-Beta 2 assays have been introduced by a number of Kit companies in an attempt to broaden the diagnostic yield.
20.5 Other Tests
Hughes Syndrome is an autoimmune disease, and other antibodies may be detected. These include ANA (common-often with accompanying Sjögren’s syndrome), anti-DNA (where APS is part of lupus), thyroid antibodies and mitochondrial antibodies (type V). Coombs’ tests for haemolytic anaemia may be positive.