Patients with
primary systemic amyloidosis (AL) often experience
bleeding, and we report a newly recognized coagulation abnormality in AL. Of 103 patients with primary systemic AL studied over 2 years, 41 had prolongation of the thrombin time (range, 25 to 46 seconds; normal, less than 22 seconds) and reptilase time (range, 17 to 39 seconds; normal, 14 to 16 seconds). The
fibrinogen from the plasma of 36 patients was precipitated by
beta-alanine and diluted to a concentration of approximately 200 mg/dL. The thrombin times of the precipitated
fibrinogens were normal in 34 patients, implying that an inhibitor was responsible for the abnormal tests. The addition of patient
fibrinogen-free plasma to normal plasma prolonged the thrombin times, and this result confirmed the presence of an inhibitor. The inhibitor is more likely to be present in patients with
nephrotic syndrome (20 of our patients) and
congestive heart failure (six). A circulating monoclonal
protein (24 patients), the presence of
amyloid liver involvement (eight), and the presence of
amyloid neuropathy (nine) were not predisposing factors. Only one patient
had deficiency of
factor X. We conclude that inhibition of
fibrinogen conversion to a
fibrin clot rather than dysfibrinogenemia is the cause of the prolonged thrombin time in primary systemic AL.