Individuals with the antiphospholipid antibody
syndrome (APS) have an increased risk for stroke, myocardial infarction,
venous thrombosis, thromboembolism, thrombocytopenia, and/or recurrent
miscarriages. In 1999, an international consensus conference found that
one criterion for the serologic diagnosis of “definite antiphospholipid
syndrome” is the presence of anticardiolipin antibody of IgG and/or IgM
isotype, at medium or high titer, on two or more occasions, at least 6
weeks apart.3 The presence of ACA of moderate to high titer
for IgG is strongly associated with both arterial and venous thrombosis
and recurrent pregnancy loss.2,4,5 The IgM isotype of ACA has also been shown to be associated with venous thrombosis.4 Other studies found that ACA of the IgA isotype at moderate to high titer can also be associated with increased risk of APS.2,6
ACA
antibodies are quite common in the general population and are not
always associated with APS. Studies indicate that there is a higher
prevalence of IgM positives than IgG in the general population with
these isotypes occurring in 9.4% and 6.5% of the population,
respectively.7 The incidence of these ACA is even higher in normal pregnancy with detection rates of 17% for IgM and 10.6% for IgG.8
Many of these antibodies are transient and not associated with APS. The
diagnosis of APS should not be made on the basis of a single ACA result
but rather on repeated positive results obtained at least six weeks
apart.1
The Venereal Disease Research Laboratory
(VDRL) agglutination test that has been used for decades in the
diagnosis of syphilis is based on the detection of antibodies to
cardiolipin.9 The first solid-phase immunoassays for ACA were developed in the early 1980s.9
These solid-phase assays are at least 100-fold more sensitive than the
classical VDRL assay and produce many more positive results. In general,
ACA are considered to be more sensitive than lupus anticoagulants (LA)
for the detection of APS.4 The ACA test is positive in 80% to 90% of patients with APS,10 and ACA are implicated in approximately five times more cases of APS than are LA;2 however, LA are considered to be more specific for APS than ACA.2,10 Due to the heterogeneity of antibodies associated with APS, both LA and ACA testing is recommend when APS is suspected.4,11
ACA
are frequently observed in patients with other autoimmune disorders and
malignancies. Individuals with ACA secondary to these other conditions
are at increased risk of developing APS. A variety of therapeutic drugs
can induce the production of ACA. These drug-induced antibodies may be
clinically significant if they persist.2,12
