Abstract
Lupus anticoagulant is a misnomer as it is commonly associated with thromboembolic events. In few cases, the name retains its literal meaning when it characterizes patients with a bleeding disorder. We describe a patient with lupus anticoagulant, hypoprothrombinemia, and major bleeding (lupus anticoagulant/hypoprothrombinemia syndrome). Immunological studies revealed a huge amount of circulating monoclonal immunoglobulin M lambda (IgMλ) antiphosphatidylserine/prothrombin antibodies (14,400 U/mL). Affinity purified monoclonal antibodies (440 U/mL) prolonged the coagulation time of normal plasma by 12.2 seconds (diluted Russell viper venom time) and 25.5 seconds (silica clotting time). The original patient's plasma mixed 1:1 with normal plasma showed a marked prolongation of coagulation times (lupus cofactor) from a ratio of 2.94 to 5.23 in diluted Russel viper venom time and from 2.30 to 3.00 using the silica clotting time. Human prothrombin added to original patient's plasma caused a marked prolongation of coagulation times in diluted Russell viper venom test thus unequivocally explaining the lupus cofactor phenomenon. In conclusion, we have shown that lupus anticoagulant/hypoprothrombinemia syndrome is attributable to monoclonal IgMλ antibodies directed to phosphatidylserine/prothrombin and that prothrombin is the protein responsible for the observed lupus cofactor phenomenon.
Highlights
Lupus anticoagulant (LA) indicates the presence of a type of “antiphospholipid antibody” that is frequently, but not always, associated with thromboembolic events
Testing for LA was remarkable as both Diluted Russell viper venom time (dRVVT) and silica clotting time (SCT) ratio further increased in mixing studies (LC)
One simple explanation might be that the coupling of ligand through primary amines determines a conformational change of the protein similar to that induced by PS and calcium ions
Summary
Lupus anticoagulant (LA) indicates the presence of a type of “antiphospholipid antibody” that is frequently, but not always, associated with thromboembolic events. LA and hypoprothrombinemia was described by Loeliger.[5] Interestingly, the mixing studies (patient plasma plus normal plasma) prolonged instead of shortening the clotting time of patient’s plasma. This phenomenon that increased the inhibitor activity by a normal plasma component was called “lupus cofactor” (LC).[6,7] Loeliger suggested that responsible for the (unknown) “cofactor” could be prothrombin (PT), while others said that LC was driven by β2‐glycoprotein I (β2‐GPI).[8] In this report, we describe a patient with LA-HPS caused by circulating antibodies against PT and prove that prothrombin is responsible for the observed LC phenomenon
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