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

Abstract

Summary. 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.

Direct Factor X sequestration by systemic amyloid light‐chain amyloidosis

“…Six to fourteen percent of AL amyloidosis patients develop an acquired Factor X (FX) deficiency 3, 4, 5. The direct binding/adsorption of FX onto amyloid fibrils has been thought to be a major mechanism for FX deficiency in amyloidosis.…”

Spontaneous rupture of the spleen in AL amyloidosis

“…reported series that have indicated Factor X deficiency in 6.3-14% of patients [26,32]. In our experience, 75% of patients with severe Factor X deficiency had hemorrhagic complications, of which 50% were severe and 17% fatal.…”

“…In a review of the literature, we have been able to identify 17 cases of splenic rupture associated with amyloidosis reported since 1948 [13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28]. Although this number does not define the actual incidence of spontaneous rupture of the spleen in amyloidosis, it suggests the splenic rupture is a rare complication in this disease.…”

Splenectomy in plasma cell dyscrasias: A review of the clinical practice

“…It has been reported to occur in 6.3-14% of these patients [24,[27][28][29]. Factor X deficiency has long been thought to result from adsorption or the in vivo binding of the factor to the amyloid fibrils [30,31].…”

“…Recent work by Mumford et al [29] has also shown that the simple adsorptive mechanism for factor X deficiency in amyloidosis may be an oversimplification, and that there may be other mechanisms, including a functional impairment of factor X.…”