[Antiphospholipid antibodies and thrombosis: the putative mechanisms of hypercoagulable state in patients with anticardiolipin antibody].
Antiphospholipid antibodies are well recognized as associated with serious clinical complications such as arterial and venous thrombosis and recurrent spontaneous abortion. These complications are collectively called antiphospholipid syndrome(APS). The mechanisms responsible for the thrombosis are unclear. We reported three mechanisms. beta 2-glycoprotein I(beta 2GPI) inhibited activated protein C(APC) activity and, furthermore, APC activity decreased by the addition of monoclonal aCL and beta 2GPI. Monoclonal anticardiolipin antibodies(aCL) seemed to enhance the inhibition of APC procoagulant activity caused by beta 2GPI. Monoclonal aCL in the presence of beta 2GPI also increased the activity of plasminogen activator inhibitor(PAI)-1 in the mixture of tissue-plasminogen activator(t-PA) and PAI-1 by inhibiting the function of beta 2GPI, which increased the remaining t-PA activity in the mixture. The formation of thrombin-antithrombin complexes(TAT) in APS was impaired. The level of TAT in APS did not increase, however the level of prothrombin fragment 1 + 2 (F1 + 2) increased. Therefore, free thrombin present in patients' blood may contribute to thrombosis in APS. These reports indicate that thrombosis in APS may be caused by several thrombogenic factors that stimulate aCL.
Ieko
M
M
Department of Internal Medicine, School of Dentistry, Health Sciences University of Hokkaido.
D017153:Antibodies, Anticardiolipin / Q000502:physiology*; D016736:Antiphospholipid Syndrome / Q000145:classification; D000990:Antithrombin III / Q000378:metabolism; D005342:Fibrinolysis; D006023:Glycoproteins / Q000502:physiology; D006801:Humans; D010447:Peptide Hydrolases / Q000378:metabolism; D017395:Plasminogen Activator Inhibitor 1 / Q000502:physiology; D011486:Protein C / Q000502:physiology; D013927:Thrombosis / Q000209:etiology*; D010959:Tissue Plasminogen Activator / Q000502:physiology; D053482:beta 2-Glycoprotein I
D017153:Antibodies, Anticardiolipin; D006023:Glycoproteins; D017395:Plasminogen Activator Inhibitor 1; D011486:Protein C; C046193:antithrombin III-protease complex; D053482:beta 2-Glycoprotein I; D000990:Antithrombin III; D010447:Peptide Hydrolases; D010959:Tissue Plasminogen Activator