Bleeding symptoms and coagulation abnormalities in 337 patients with AL-amyloidosis

Haemorrhage is a frequent manifestation of amyloidosis. We performed a retr ospective clinical analysis of 337 patients with systemic immunoglobulin li ght-chain (AL)-amyloidosis, in whom whole-body serum amyloid P component (S AP) scintigraphy and a clotting screen had been performed. Abnormal bleedin g was noted in 94 cases (28%), and the coagulation screen was abnormal in 1 72 cases (51%). The most common abnormalities were prolongation of the thro mbin time (TT; 108 cases, 32%) and the prothrombin time (PT: 82 cases, 24%) . In multivariate analysis, a prolonged PT was the only coagulation abnorma lity associated with abnormal bleeding (P = 0.0012). but this was independe nt of the whole-body amyloid toad. Prolongation of the TT was associated wi th hepatic amyloid infiltration (P < 0.00001), with proteinuria (P < 0.001) and low serum albumin (P < 0.00001). In 154 patients who were studied furt her, subnormal factor X activity (FX:C) nas found in 22 cases (14%). In cas es with subnormal FX:C, the corresponding factor X antigen (FX:Ag) measurem ents 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 coagulatio n are common in AL-amyloidosis and are multifactorial in origin. We provide evidence suggesting that hepatic amyloid infiltration and nephrotic syndro me 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 red uction in FX:Ag.