Laboratory diagnosis of lupus anticoagulants.

Circulating anticoagulants or inhibitors of clotting factors are defined as endogenously produced substances that interfere with various in vitro tests of coagulation. Anticoagulants are usually immunoglobulins, although other endogenous materials, such as heparin or fibrinogen split products, may inhibit in vivo or in vitro coagulation (Table 1). Specific inhibitors are immunoglobulins with epitope specificity for a single coagulation protein. These inhibitors may be neutralizing or nonneutralizing. The most common specific inhibitors are auto or alloantibodies to Factor VIII. It is imperative to identify correctly Factor VIII inhibitors, since they are associated with significant clinical bleeding. Nonspecific inhibitors, such as lupus anticoagulants (LA) are not directed at any single coagulation protein and they are generally not associated with bleeding. Conley and Hartmann first reported an association between circulating anticoagulants and systemic lupus erythematosus (SLE). Their first case report emphasized a correlation with bleeding; however, subsequent studies have shown that these patients generally do not have a bleeding tendency attributable to the coagulation inhibitor. The term "Iupus anticoagulant" was suggested in 1972 by Feinstein and Rapaport. It is, however, an unfortunate misnomer, since the majority of patients do not have SLE and, in the absence of other hemostatic abnormalities, the patients do not bleed. Since patients with LA generally lack hemorrhagic symptoms, clinicians and laboratories initially regarded LA as a nuisance. However, laboratories were required to investigate the causes of abnormal activated partial thromboplastin times (APTT). Often the evaluation of the abnormal APTT involved multiple factor assays and time-consuming mixing studies yielded inconclusive or confusing results. Thus, some reagent manufacturers designed their reagents to be insensitive to the presence of LA. Paradoxically, LA was subsequently found to be associated with both arterial and venous thrombosis as well as recurrent pregnancy loss. Consequently, laboratories are now receiving requests to evaluate patients for the presence of LA. This review will focus on the characterization, clinical associations, and laboratory diagnosis of LA.