Screening for the lupus anticoagulant

Abstract

The lupus anticoagulant may be defined as an immunoglobulin (IgG, IgM or both) which interferes with one or more of the in vitro phospholipid-dependent tests of coagulation. For many years, lupus anticoagulants were regarded as a laboratory nuisance; consequently, reagents were often selected on the basis of insensitivity to lupus anticoagulants. Recently, lupus anticoagulants have been associated with a variety of clinical conditions including recurrent thromboembolic events (both arterial and venous), obstetrical complications including fetal death and spontaneous abortion, and a variety of hematologic and neurologic complications. As a result, many laboratories are now being asked to identify the presence of lupus anticoagulants in selected patient populations. In addition to assays for lupus anticoagulants, there are immunologic assays designed to detect phospholipid antibodies using solid phase systems (RIA or ELISA). A variety of screening tests have been designed to enhance sensitivity to lupus anticoagulants. Test systems with decreased amounts of phospholipid (phosphatidylserine) appear to be most sensitive to lupus anticoagulants. Of the various tests used, the activated partial thromboplastin time (APTT) appears to be most sensitive. The sensitivity of any screening test system is inversely proportional to the residual platelets in the patient sample. APTT reagents differ widely in their sensitivity to lupus anticoagulants. The dilute Russell viper venom time is also highly dependent on the choice and concentration of phospholipid with respect to its sensitivity. Once an abnormality of a screening test has been identified, it is necessary to prove the abnormal result is due to the presence of an inhibitor. This step in the diagnosis may utilize either mixing studies or plasma agarose gels. The final step in the diagnosis of lupus anticoagulants is the demonstration of phospholipid specificity of the inhibitor. Two approaches have been utilized: 1. test systems designed to enhance anticoagulant effect (phospholipid-depleted), and 2. test systems with increased or altered phospholipids which will bypass or neutralize the anticoagulant.