Excessive fibrinolysis in AL-amyloidosis is induced by urokinae-type plasminogen activator from bone marrow plasma cells.
Activation of fibrinolysis system and excessive fibrinolysis are observed in monoclonal antibody light chain (AL)-amyloidosis. However, the mechanisms by which activation of fibrinolysis occurs in AL-amyloidosis have not been fully elucidated. To determine whether urokinase type-plasminogen activator (uPA), an important activator of fibrinolytic system, contributes to the activation of fibrinolytic system in AL-amyloidosis, we immunohistologically examined uPA in bone marrow plasma cells. More than 90% of bone marrow plasma cells from five different AL-amyloidosis patients were uPA-positive as examined with immunohistochemical staining. All the bone marrow plasma cells from seven different patients with multiple myeloma were uPA-negative. A patient with AL-amyloidosis, who had bleeding diathesis and excessive fibrinolysis with hypofibrinogenemia, was treated with nafamostat mesilate, a potential inhibitor of uPA. After the administration of nafamostat mesilate, the bleeding diathesis disappeared, and excessive fibrinolysis and hypofibrinogenemia were improved. The present data suggested that uPA expressed in plasma cells may have contributed to the pathogenesis of excessive fibrinolysis.
Uchiba
Mitsuhiro
M
Department of Blood Transfusion and Cell Therapy, Kumamoto University Hospital, Kumamoto, Japan. mituhiro-uchiba@fc.kuh.kumamoto-u.ac.jp
Imamura
Takahisa
T
Hata
Hiroyuki
H
Tatetsu
Hiro
H
Yonemura
Yuji
Y
Ueda
Mitsuharu
M
Wada
Yoshihiro
Y
Mitsuya
Hiroaki
H
Ando
Yukio
Y
D000368:Aged; D000686:Amyloidosis / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology*; D001854:Bone Marrow Cells / Q000201:enzymology*; D005342:Fibrinolysis; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism*
D014568:Urokinase-Type Plasminogen Activator