A monoclonal immunoglobulin A (kappa) factor VIII:C inhibitor associated with primary amyloidosis: identification and...

Factor VIII:C inhibitors associated with primary amyloidosis have not been previously reported. A patient with autopsy-proved primary amyloidosis developed renal failure requiring peritoneal dialysis. Purpura and a prolonged partial thromboplastin time (PTT) were first observed 3 years later, after treatment was changed from peritoneal dialysis to hemodialysis. Plasma contained a time-dependent factor VIII:C inhibitor. The inhibitor on isoelectric focusing showed two peaks of activity, one with an isoelectric point (pl) of approximately 4 and the second larger, with a pl of approximately 8. Both were neutralized only by antisera to IgA and kappa light chain. A monoclonal antibody prepared in Balb/c mice against the variable region of the kappa light chain also blocked the inhibitor. The delayed onset of the coagulopathy could be explained by the change from peritoneal to hemodialysis, because in the former, significant amounts of the paraprotein, indicated by an "M-spike," were recovered in the dialysate. N-terminal amino acid sequencing of the first 20 amino acids of the variable region of the kappa light chain from the urinary protein and the splenic amyloid subunit showed identity.