Clotting alterations in primary systemic amyloidosis.

Background and Objectives. The bleeding manifestations frequently observed in patients with immunoglobulin light chain amyloidosis (AL) have been attributed to different pathogenetic factors: amyloid deposits in several organs and systems leading to failures of these latter, the affinity of amyloid for some clotting factors, and the presence of plasma components interfering with fibrin formation could all induce alterations of clotting tests. This investigation was aimed at defining the prevalence of clotting abnormalities and their clinical manifestations in patients with AL. Design and Methods. Thirty-six consecutive patients with biopsy proven amyloidosis and documented monoclonal gammapathy were enrolled within one year The following clotting tests were considered in the study activated partial thromboplastin time (aPTT), prothrombin time (PT), thrombin time (TT), reptilase time (RT), Russell's viper venom time (RVTT), fibrinogen, factor X and alpha-2 antiplasmin. Results. Hemorrhagic manifestations were mild to moderate in nine patients, but severe and untractable in one. The most frequent clotting anomaly was defective fibrinogen conversion to fibrin, as demonstrated by prolongation of both TT (85% of cases) and RT (90% of cases). Low levels of actor X activity were observed in about 1 out of 4 samples, while fibrinogen and alpha2 antiplasmin levels were distributed over a wide range of values. PT was prolonged in 8 and aPTT in 25 patients. The search for lupus anticoagulant was negative in samples showing a prolongation of aPTT and/or RVVT. Interpretation and Conclusions. The prolongation of TT and RT is not dependent on either the presence of a heparin-like substance in the plasma or an fibrinogen levels; furthermore, the prolongation of RVVT is not related to factor X level. The hypothesized presence in the plasma of an inhibitor of fibrin formation could also affect factor X activation by Russell viper venom. The prolongation of TT and RT represents a peculiar feature of amyloidosis. The variability in the behavior of the other clotting times and hemostatic factors studied is mirrored in the heterogeneity of the clinical features observed in this disease.