Haemorrhage is a frequent manifestation of
amyloidosis. We performed a retrospective clinical analysis of 337 patients with systemic
immunoglobulin light-chain (
AL)-amyloidosis, in whom whole-body
serum amyloid P component (SAP) scintigraphy and a clotting screen had been performed. Abnormal
bleeding was noted in 94 cases (28%), and the coagulation screen was abnormal in 172 cases (51%). The most common abnormalities were prolongation of the thrombin time (TT; 108 cases, 32%) and the prothrombin time (PT; 82 cases, 24%). In multivariate analysis, a prolonged PT was the only coagulation abnormality associated with abnormal
bleeding (P = 0.0012), but this was independent of the whole-body
amyloid load. Prolongation of the TT was associated with hepatic
amyloid infiltration (P < 0.00001), with
proteinuria (P < 0.001) and low
serum albumin (P < 0.00001). In 154 patients who were studied further, subnormal
factor X activity (FX:C) was found in 22 cases (14%). In cases with subnormal FX:C, the corresponding
factor X antigen (FX:Ag) measurements were consistently higher (median FX:Ag/FX:C 2.5, range 0.81-9.25, n = 16) than cases with normal FX:C (median FX:Ag/FX:C 0.96, range 0.65-1.29, n = 28, P < 0.0001). No evidence was found of an FX inhibitor. Of the 48/154 (31%) cases with a prolonged TT, the reptilase time was also prolonged in 38/48 cases (79%). These data show that haemorrhage and abnormal coagulation are common in
AL-amyloidosis and are multifactorial in origin. We provide evidence suggesting that hepatic
amyloid infiltration and
nephrotic syndrome are determinants of the TT. In most patients, prolongation of the PT was explained by reduction in FX:C, but this was not wholly explained by a reduction in FX:Ag.