Increase in plasma thrombin-activatable fibrinolysis inhibitor may not contribute to thrombotic tendency in antiphospholipid syndrome because of inhibitory potential of antiphospholipid antibodies toward TAFI activation.
The causes of thrombosis in antiphospholipid syndrome (APS) remain unknown, though several hypotheses in regard to hypofibrinolysis have been proposed. To clarify the mechanism, we measured plasma levels of thrombin-activatable fibrinolysis inhibitor (TAFI) in APS patients. Both the TAFI antigen (TAFI:Ag) level measured with an ELISA, and thrombin-thrombomodulin-dependent TAFI activity (TAFI:Ac) were elevated in 68 APS patients as compared with those in 66 healthy controls, though they were lower than those in 46 patients with autoimmune diseases. As for the influence of antiphospholipid antibodies (aPL) on TAFI levels, the mean TAFI:Ac level in 39 SLE patients positive for APS was significantly lower than that in 27 SLE patients without APS, whereas there was no difference in TAFI:Ag between those groups. Furthermore, purified IgG from patients positive for aPL, and monoclonal aPL (EY2C9 and 23-1D) inhibited the activation of TAFI in a concentration dependent manner. These results suggest that aPL inhibits TAFI activation by affecting the function of thrombomodulin-thrombin complex through phospholipids. Although TAFI in plasma is elevated in autoimmune diseases including APS, we concluded that an elevated level is not likely a risk factor for thrombosis in APS patients, because of the inhibition of TAFI activation by aPL.
Ieko
Masahiro
M
Department of Internal Medicine, School of Dentistry, Health Sciences University of Hokkaido, 1757-Kanazawa, Ishikari-Tobetsu, Hokkaido, 061-0293, Japan. iekom@hoku-iryo-u.ac.jp
Yoshida
Mika
M
Naito
Sumiyoshi
S
Nakabayashi
Toru
T
Kanazawa
Kaoru
K
Mizukami
Kazuhiro
K
Mukai
Masaya
M
Atsumi
Tatsuya
T
Koike
Takao
T
D000328:Adult; D000368:Aged; D017152:Antibodies, Antiphospholipid / Q000276:immunology*; D016736:Antiphospholipid Syndrome / Q000097:blood* / Q000150:complications; D025901:Carboxypeptidase B2 / Q000097:blood* / Q000276:immunology; D005260:Female; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000097:blood; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D013927:Thrombosis / Q000209:etiology*
D017152:Antibodies, Antiphospholipid; D025901:Carboxypeptidase B2