AntiCardiolipin (Anti-phospholipid) Antibody
The presence of anticardiolipin antibody (ACA) has been associated with recurrent arterial and venous thrombosis, recurrent fetal loss, thrombocytopenia, neurologic events including transient ischemic attack (TIA) and stroke, and dermatologic disease, primarily livedo reticularis. In addition to testing for lupus anticoagulant, immunologic methods can be used to detect anticardiolipin antibody.
Diagnostic criteria for the antiphospholipid syndrome include both clinical and laboratory findings. At least one of the following clinical criteria must be met; arterial or venous thrombosis, pulmonary hypertension, livedo reticularis, TIA or stroke, recurrent fetal loss, or thrombocytopenia. Laboratory findings must include positive tests for lupus anticoagulant and/or anticardiolipin antibody. Anticardiolipin antibody and lupus anticoagulant tests are discordant in approximately 30% of patients. Positive results with either of these assays should be regarded as independent risk factors for a thrombotic tendency. Positive results with both tests do not connote a greater risk of thrombosis than a single positive test. The anticardiolipin antibody test is more useful than the lupus anti-coagulant to follow patients undergoing immunosuppressive treatment.
A close relationship has been established between thrombotic events and the presence of anticardiolipin antibodies (ACA). There is little information, however, on the prevalence and clinical significance of ACA in healthy subjects. In a recent study, 552 healthy blood donors were screened for the presence of ACA (by ELISA). ACA positive donors were monitored every 3 months for one year for persistence of ACA, and for presence of lupus anticoagulant, ANA, antibodies to double stranded DNA, rheumatoid factor, and various viral and bacterial serological tests. The prevalence of IgG ACA in a healthy population was 6.5% and 9.4% for IgM ACA. ACA levels declined progressively, with only 4 donors positive for IgG ACA and 1 positive for IgM ACA after one year of follow-up. No subjects were positive for lupus anticoagulant or any of the other autoantibodies or serological tests performed. Only 5 donors with IgG ACA and 4 with IgM ACA had a family, but not personal history of thrombosis, and only 1 donor with IgG ACA and 2 with IgM ACA had a past history of unexplained miscarriages. The relative absence of clinical complications in the subjects positive for ACA suggests that additional risk factors may be present when thrombotic complications occur. This study indicates a significant prevalence of ACA in healthy subjects, with no apparent clinical manifestations. In this situation, ACA may represent natural antibodies, or an immune system that is functioning normally.
There is strong evidence linking ACA with venous thromboembolism in patients with SLE, however evidence linking ACA with venous thromboembolism (VTE) in patients without SLE is limited. It has also been suggested that non-SLE patients with ACA and VTE are resistant to usual intensities of warfarin therapy, which has prompted more intense anticoagulation of these patients by many physicians. In a recent study addressing these issues, 244 patients with a first episode of clinically suspected deep vein thrombosis or pulmonary embolism were evaluated with objective tests for VTE, and laboratory tests for both LA and ACA. The patients with proven VTE were treated with usual intensities and duration of anticoagulants, and were followed prospectively for recurrence of VTE both during and after discontinuation of anticoagulants.
The investigators observed a strong and statistically significant association between the presence of LA and VTE, with a relatively high prevalence of LA in patients with VTE (14%), versus those without VTE (2%). On the other hand, there was no association between ACA and VTE, with an equally high prevalence of ACA in those with (14%) and without (18%) VTE. The authors also noted that none of the patients with VTE and ACA developed recurrent VTE while on warfarin therapy. Furthermore, there was no difference between those with and without ACA in the recurrence rate of VTE after warfarin anticoagulation was discontinued.
The findings in this study support the use of laboratory tests for LA in the evaluation of patients with VTE. The results suggest, however, that testing for ACA in this situation may not be clinically useful, in view of the high prevalence of abnormal results in patients without VTE. It is possible that some of these positive ACA results are transient - a longer-term study would be required to evaluate a possible relationship between persistent ACA positivity and VTE. The findings also suggest that the presence of APA in patients with VTE is not associated with resistance to a conventional intensity of warfarin therapy or an increased risk of recurrent VTE, and do not support the use of more intense anticoagulation in these patients. The authors caution, however, that a larger study is required to address these treatment issues.
Information on the prevalence and clinical significance of IgA ACLA is contradictory. Some studies have indicated that these antibodies have a low prevalence and are of little if any clinical importance, while others have suggested possible clinical significance. A recent study sought to evaluate the usefulness of IgA ACLA as markers of thrombosis and/or the APLA syndrome. ELISA tests for IgG, IgM, and IgA ACLA, and coagulation tests for lupus anticoagulant were performed in 795 patients (255 with autoimmune diseases including SLE and primary APLA syndrome, 153 with deep vein thrombosis, 108 with transient ischemic attacks, 196 with obstetric complications including recurrent fetal loss and retarded fetal growth, and 83 with infectious diseases including syphilis and HIV infection) and 81 healthy laboratory workers. IgA ACLA were positive in only two patients (0.25% of the whole patient group), both of whom had SLE, and both of whom were also positive for IgG ACLA. IGA ACLA was not detected in any other patient group, or in the control subjects.
The authors conclude that the incidence of IgA ACLA is extremely low, and that their determination is not helpful in the investigation of thrombosis or other manifestations of the APLA syndrome. Testing for IgA ACLA was recently discontinued in Saint Luke’s Regional Laboratories due to our similar finding of low prevalence of these antibodies. The ACA panel includes only IgG and IgM antibodies.
Clinically significant anticardiolipin antibodies that cause thrombosis usually have the following characteristics.
- IgG class
- Persistently present for more than two months
- High titer (>40 GPL units)
- Associated with anti-beta 2 glycoprotein 1 antibody
Reference range is 0 - 20 GPL units and 0 - 10 MPL units.
Specimen requirement is one SST tube of blood.
