Correlation between lupus anticoagulants and anticardiolipin antibodies in patients with prolonged activated partial thromboplastin times

PURPOSE: An increased incidence of thrombosis has been reported in patients with a prolonged activated partial thromboplastin time (APTT) due to a lupus anticoagulant (LA), which is an antibody to negatively charged phospholipids. The antiphospholipid antibodies can be quantitated in an enzyme-linked immunoabsorbent assay (ELISA) that utilizes cardiolipin as the antigen. With the development of the ELISA, two major areas of controversy have arisen. First, the correlation between assay results for LA and for the ELISA has varied widely among laboratories. Second, some investigators have described a correlation between high levels of anticardiolipin antibodies (ACA) and thrombotic disorders, whereas others have found no association between ACA levels and thrombosis in a general population of medical patients. To explore these issues further, the present study determined the sensitivity and specificity of an LA assay for detecting ACA in medical patients with a prolonged APTT. The association between the isotype and titer of ACA and thrombosis was examined in those patients positive for LA. PATIENTS AND METHODS: Plasma samples from 70 medical patients with a prolonged APTT by routine screening studies were tested for the presence of LA by dilution of phospholipid in an APTT system and for IgM and IgG ACA according to a standardized ELISA. Clinical records were reviewed for a history of thrombotic events by an investigator who had no knowledge of the laboratory results. RESULTS: The ACA assay gave positive results in 47 patients, 44 of whom also tested positive for LA. Thus, the sensitivity for the LA assay for detecting ACA was 94 % (confidence interval, 82 % to 99 %). The result of the LA assay was negative in 20 of 23 patients who were ACA-negative. The specificity of the LA assay was 87 % confidence interval, 67 % to 98%). Twelve of the 47 patients (26%) had a history of venous or arterial thrombosis. Of these Patients, 75% tested in the high-positive range for IgG or IgM ACA, or both. Of the 35 patients without thrombosis, only 14% were in this range. Patients with thrombosis had either underlying systemic lupus erythematosus, lymphoma, or no apparent etiology for IA. There was no history of thrombosis in patients with LA associated with infection or medication. CONCLUSION: A test for LA in medical patients with a proloned APFT can be sensitive and specific for ACA. Determination Of ACA levels in patients who have LA that is not induced by medication or infection may define those patients at increased risk for thrombosis.
Activated partial thromboplastin time (APTT) is the time required for a clot to form after the blood clotting factor thromboplastin, calcium and a phospholipid are added to a blood sample. Normal values range from 16 to 40 seconds, with prolonged times indicating blood clotting abnormalities. The incidence of thrombosis or blood clotting may be increased in patients with prolonged APTT due to a lupus anticoagulant (LA), an antiphospholipid antibody or specialized protein that specifically binds to and inactivates phosphate-containing compounds. The antiphospholipid antibodies can be measured using an immunological test called the enzyme-linked immunoabsorbent assay (ELISA) that uses cardiolipin as the phospholipid. However, studies have not consistently shown a correlation between direct measurements of LA and results from cardiolipin-dependent ELISA or an association between anticardiolipin antibodies (ACA) and thrombosis. The sensitivity and specificity of an LA assay for detecting ACA was evaluated in 70 patients with a prolonged APTT. The LA assay was shown to be 94 percent sensitive and 87 percent specific for detecting ACA. ACA were detected in 75 percent of 12 patients with thrombosis and 14 percent of 35 patients without thromboses. Patients with LA due to infection or medication had no thrombosis. The findings demonstrate that a test for LA in patients with prolonged APTT is sensitive and specific for measuring ACA levels, which may indicate the risk for thromboses in patients with LA unrelated to infection or medication. (Consumer Summary produced by Reliance Medical Information, Inc.)