Lupus Anticoagulants and Their Relationship with the Inhibitors against Coagulation Factor VIII: Considerations on the Differentiation between the 2 Circulating Anticoagulants

Lupus anticoagulants (LAs) are a heterogeneous group of immunoglobulins directed against negatively charged phospholipids in complex with proteins [β2-glycoprotein I (β2GPI), prothrombin and others] (1). LAs prolong phospholipid-dependent coagulation tests and are associated with increased risk of thrombosis and fetal loss (1). There are other types of anti-phospholipid (aPL) antibodies with or without LA activity that are detected by ELISAs that use as capture antigen cardiolipin, β2GPI, or prothrombin (1). Although the exact distribution of the 2 types of antibodies is unknown, it is widely accepted that LAs and aPL antibodies coexist in a large number of patients classified as having the antiphospholipid syndrome.The relationship of these factors to inhibitors of individual coagulation factors seen in other conditions is controversial. Among the inhibitors of individual coagulation factors, those that inhibit factor VIII (anti-FVIII) are the most frequent, with an estimated incidence of 30% in patients with severe hemophilia A (2). They may also occur in nonhemophiliacs, producing a clinical condition known as acquired hemophilia (2). Anti-FVIII inhibitors bind to FVIII over a period of time and are associated with the risk of bleeding (3). Although LA and anti-FVIII inhibitors are dissimilar in terms of target and clinical presentation, they are somewhat related, as both of them prolong the phospholipid-dependent coagulation tests. Over the years there has been much debate on the possibility that some hemophiliacs may bear both types of anticoagulants (4)(5)(6), but this is still an unresolved question because tests to detect LA without interference from the anti-FVIII inhibitors are lacking (7).In an attempt to clarify these issues and to explore the suitability of current diagnostic strategies to differentiate LAs from specific inhibitors to coagulation factors, we used a variety of phospholipid-dependent tests to detect LA …