Abnormalities in thrombin-antithrombin pathway in AL amyloidosis.
Various pathogenic factors have been proposed to explain the abnormal hemostasis observed in AL amyloidosis. Since imbalance between clotting factors and inhibitors could play a pathogenic role in both hemorrhagic and thrombotic manifestations, we investigated the thrombin-antithrombin pathway in 35 patients with AL amyloidosis. Ten patients suffered from bleeding while 3 patients experienced deep venous thrombosis. Thrombin time was prolonged in 29 subjects, the mean values of antithrombin III activity (ATIII Act) were significantly lower than those of antithrombin III antigen (ATIII Ag) with loss of relationship between these two different techniques of ATIII detection, normally observed in healthy controls. In 19 patients increased levels of thrombin-antithrombin (TAT) complexes were present. Crossed immunoelectrophoresis of ATIII, performed in presence of heparin, evidenced ATIII forms with reduced binding capacity to heparin and TAT complexes of various electrophoretic mobilities. In conclusion, the impairment of the thrombin-antithrombin pathway, in association with the low ATIII biological activity, might play a pathogenic role in the hypercoagulable state reported in AL amyloidosis, despite the higher frequency of bleeding manifestations.
Gamba
G
G
Department of Internal Medicine, University of Pavia, IRCCS Policlinico San Matteo, Italy.
Montani
N
N
Anesi
E
E
Palladini
G
G
Lorenzutti
F
F
Perfetti
V
V
Merlini
G
G
D000328:Adult; D000368:Aged; D000682:Amyloid / Q000097:blood / Q000652:urine; D000686:Amyloidosis / Q000150:complications / Q000378:metabolism*; D000990:Antithrombin III / Q000378:metabolism*; D020147:Coagulation Protein Disorders / Q000503:physiopathology; D005260:Female; D006493:Heparin / Q000378:metabolism; D006801:Humans; D007122:Immunoelectrophoresis; D008297:Male; D008875:Middle Aged; D010447:Peptide Hydrolases / Q000378:metabolism*; D011485:Protein Binding; D013918:Thrombin Time
D000682:Amyloid; C046193:antithrombin III-protease complex; D000990:Antithrombin III; D006493:Heparin; D010447:Peptide Hydrolases