Based on Miyakis S et al. (2006) International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). Journal of Thrombosis and Haemostasis 4: 295-306.

C. The anticardiolipin antibody (aCL) test   

This measures antibodies in serum. SydPath only measures IgG antibodies, which are clinically the most important. If “anti-phospholipid antibodies” are requested, the aCL IgG antibody test will be performed.  aCL assays are prone to significant variability.  Samples from the same patient tested at different times or in different laboratories may show substantially different values.  Additionally, aCL may transiently appear during or after a variety of infectious, inflammatory and malignant diseases, in which case they are not associated with increased risk of thrombosis.  If a positive result is obtained the test should be repeated at least 12  weeks later before making the diagnosis of antiphospholipid syndrome.

In the absence of clinical features, the detection of aCL does not signify the presence of the anti-phospholipid syndrome, but it does signify a risk factor for having or developing this condition; in general, the higher the aCL value, the higher the risk of thromboembolic disease.  SydPath provides a numerical aCL value, and a table indicating the ranges of low, medium and high values. An aCL result in the "high" bracket on two occasions at least 12 weeks apart is strongly associated with clinical features of anti-phospholipid syndrome. aCL results in the "low" zone carry much less weight and are of uncertain significance.  Interpretation can be assisted by measurement of b2GP1 and LA.

D. Antibodies to b2GP1

Cardiolipin binds to a serum protein called b2GP1.  In patients with the antiphospholipid syndrome, anti-cardiolipin antibodies are associated with antibodies to b2GP1.  Therefore in patients who are positive for aCL, it is important to test for antibodies to b2GP1.  As with aCL, SydPath only measures IgG antibodies. This test is probably more specific than aCL for the diagnosis of the antiphospholipid syndrome.  However, the anti-b2GP1 antibody test has less sensitivity, and is not suitable as a single screening test for the antiphospholipid syndrome.

E. The lupus anticoagulant (LA) test  

Patients with antiphospholipid syndrome experience thromboembolic disease, but paradoxically their plasma exhibits prolonged clotting times in certain laboratory tests.  When the LA test is ordered, specific functional coagulation assays are performed on plasma.  Patients with LA exhibit prolonged coagulation times in phospholipid-dependent assays.  The abnormalities do not correct upon mixing with normal plasma, but they do correct in the presence of excess phospholipid.  Patients may sometimes be positive for LA, but negative in the other tests.  Recent studies have suggested that LA may be more strongly associated with thromboembolic disease than antibodies to cardiolipin or b2GP1.

When LA is requested, SydPath performs two tests - the dilute Russell’s Viper Venom Time (dRVVT) and the Tissue Thromboplastin Inhibition test (TTI) as well as a coagulation screen (PT and APTT).   The laboratory requires one citrate tube for LA testing; the coaulation screen can be performed on the same tube.  Only one of dRVVT or TTI needs to be positive to report that the patient has an LA.  SydPath reports positive LA results as weak, moderate or strong.  LA is one of the causes of a prolonged APTT that does not correct upon mixing with normal plasma.  However, the presence of a normal APTT does not exclude LA, and specific LA testing should always be requested. It is possible to perform LA testing on patients who are receiving anticoagulant therapy with unfractionated heparin, low molecular weight heparin or warfarin. However, a weak LA may be missed in these circumstances, hence it is advisable to repeat testing once the patient ceases anticoagulant therapy.

F. Test ordering and interpretation

There may be a correlation between results in the assays, but often, patients with anti-phospholipid syndrome are positive in only one assay.   Therefore if the syndrome is suspected, all assays (aCL, b2GPI and LA)should be requested. Caution needs to be exercised in interpretation of results because low level positive results are common and of dubious significance. Additionally, the APL syndrome cannot be diagnosed on test results alone, but requires compatible clinical features. The presence of high levels of antibodies, even if not associated with clinical features, probably does represent a major risk factor for future thromboembolic events, and expert assessment of the patient is advisable.