Considerations for simultaneous detection of autoantibodies to coagulation factor and lupus anticoagulant

Abstract

In patients with autoimmune coagulation factor deficiency (AiCFD), the production of autoantibodies that inhibit coagulation factors in the blood reduces the activity of those relevant coagulation factors, resulting in severe bleeding symptoms. Recently, reports of patients with AiCFD have noted the concomitant detection of lupus anticoagulant (LA), a risk factor for thrombosis. LA-positive patients may show bleeding symptoms due to decreased activity of coagulation factor II (FII) caused by autoantibodies against FII, in addition to thrombotic symptoms, a condition termed LA-hypoprothrombinemia syndrome (LAHPS). Anti-FII antibodies in LAHPS cases are frequently cleared antibodies that can be detected using immunological techniques, such as enzyme-linked immunosorbent assay (ELISA). Recently, several cases of coagulation FV inhibitors, known as autoimmune FV deficiency, have been reported. Some of these cases may be complicated by LA, which can cause thrombosis. False-positive results for anticoagulant inhibitors are known to occur in LA cases; therefore, immunological confirmation of antibodies against coagulation factors is recommended. Additionally, acquired hemophilia A (AHA), caused by autoantibodies against FVIII, is a typical acquired hemorrhagic diathesis, although affected patients may present with thrombosis associated with LA. Thus, it is important to remember that hemorrhagic diathesis due to autoantibodies against clotting factors can also result in thrombosis, as demonstrated by the co-detection of LA. When clotting factor inhibitors are detected in LA-positive individuals, it is important to confirm the presence of autoantibodies against coagulation factors using immunological methods, such as ELISA, to avoid false-positive results.

Diagnosis and Treatment of Autoimmune Acquired Coagulation Factor Deficiencies: An Evidence-Based Review of Japanese Practice

“…22 36 37 Approximately 4% of patients with AiF5D reported unmeasurable for lupus anticoagulant (LA) 22 because of extremely prolonged clotting times, 33 thereby requiring diagnostic caution. 38 For example, 8 out of 13 (54%) of AiF5D patients had a diluted Russell viper venom time (dRVVT) of more than 200 and 130 seconds (T1 without excess phospholipid and T2 with excess phospholipid, respectively) measured by a commercial laboratory service (SRL Ltd., Hachioji, Japan) using the LA Test Gradipoa (MBL, Ina, Japan; reference range of T1/T2, <1.3). In contrast, all 18 AiF8D patients showed a T1 of dRVVT between 35.8 and 82.7 seconds and a T2 of dRVVT between 35.3 and 75.4 seconds (mean and standard deviation of T1/T2; 1.15 and 0.11).…”