Light-chain paraproteins with lupus anticoagulant activity

A patient with newly diagnosed multiple myeloma manifested by urine kappa light-chain excretion and a small monoclonal spike (0.4 g/dl), presented with lower extremity deep venous thrombosis. A preheparin plasma-activated partial thromboplastin time (aPTT) was prolonged at 68 sec (normal control 26-42 sec). Additional studies confirmed the presence of lupus anticoagulant activity in the serum: the modified Russell Viper Venom Time (MRVVT) was 73 sec (normal control 24-42 sec) and with a 50:50 mix of the patient's plasma and pooled normal plasma, the MRVVT remained prolonged. Kappa light chains (LC) were isolated from the patient's urine and their purity confirmed by electrophoresis and immunofixation using specific immunoglobulin antisera. The patient's LC mixed with pooled normal plasma demonstrated LA activity by in vitro clotting tests (plasma-activated partial thromboplastin time 62 sec, with normal control of 45 sec), MRVVT of 44 sec with normal control of 35 sec. Purified urinary kappa light chains from a control patient with multiple myeloma and normal clotting studies, failed to prolong either the plasma-activated partial thromboplastin time or the MRVVT. We hypothesize that kappa LC in our patient demonstrated LA activity, which was unique to these LCs. Paraproteins with LA activity, to date, have included only intact immunoglobulins (Ig). While intact Ig paraproteins have been reported to possess LA activity, this is the first report to our knowledge of light-chain paraproteins possessing similar activity and resulting in clinically evident thrombosis. Light chain paraproteins could serve as useful models for further study of the mechanisms of activity of acquired LA inhibitors.