ACQUIRED FREE PROTEIN-S DEFICIENCY ASSOCIATED WITH MULTIPLE-MYELOMA -A CASE-REPORT

Investigation of recurrent venous thromboembolic events in a 46-year-o ld man with progressive IgG kappa (total serum IgG, 74.3 mg/ml) multip le myeloma revealed profound reductions in free protein S (PS) antigen (<0.1 U/ml) and PS activity (0.33 U/ml). Total PS antigen, protein C, antithrombin III, and C4b-binding protein levels were within normal l imits. The patient had no family history suggestive of a congenital PS deficiency and no history of thrombosis predating the diagnosis of hi s plasma cell dyscrasia. Patient IgG was isolated from serum using a p rotein A-sepharose affinity column and characterized. PS-dependent clo tting assays (Staclot Protein S, Diagnostics Stage, Asnieres sur-Seine , France) performed on normal pooled plasma mixed with dilutions of pa tient IgG (0.0-33.0 mg/ml) revealed is dose-dependent neutralization o f PS activity by 43%. Total and free PS antigen levels were measured u sing Laurell rocket electroimmunodiffusion (Assera-Plate Protein S, Di agnostics Stage), which revealed a similar dose-dependent reduction in free PS antigen but preserved normal total PS antigen. Free PS antige n was reduced by 77% to 0.23 U/ml using an IgG concentration (16.5 mg/ ml) less than one-fourth of that of the patient at time of serum colle ction. Specific binding of the patient IgG to commercially available p urified human PS was demonstrated by Western immunoblot analysis. Wher eas acquired free PS deficiency has been previously reported in associ ation with nephrotic syndrome, inflammatory bowel disease, HIV infecti on, and varicella infection, this is the first reported case of a hype rcoagulable syndrome associated with acquired free PS deficiency a,nd multiple myeloma. (C) 1996 Wiley-Liss, Inc.