title: Aberrations of the tissue factor pathway in patients positive for lupus anticoagulant.
abstract: To evaluate the relationship between the tissue factor (TF) pathway and lupus anticoagulant (LA), in the present study, we measured the plasma levels of TF antigen and TF pathway inhibitor (TFPI) antigen in patients positive for LA. Plasma TF and TFPI levels in LA-positive patients were significantly higher than levels in healthy volunteers (p < 0.01). In LA-positive patients, there were no significant differences in plasma TF and TFPI levels between patients with and without thrombosis. In patients with thrombosis, there was no significant difference in the plasma TF level between LA-positive and LA-negative patients; however, the plasma TFPI level in LA-positive patients was significantly lower than that in LA-negative patients (p < 0.01). We also examined the TF pathway in human umbilical venous endothelial cells (HUVEC) incubated with plasma of LA-positive patients, LA-negative patients, and healthy volunteers. TF activity was significantly higher (p < .05) in HUVECs incubated with the plasma of LA-positive patients than in cells incubated with the plasma of the other two groups (p < .01). However, there was no significant difference in TFPI antigen levels among the media of HUVECs incubated with the plasma of all groups. The viability of HUVEC incubated with the plasma of LA-positive patients with thromboses, LA-positive patients without thromboses, and LA-negative patients with thromboses were significantly lower than that of HUVECs incubated with the plasma of healthy volunteers (p < .01). These findings suggest that abnormalities of the TF pathway plays an important role in the mechanism of hypercoagulability in LA-positive patients. LA may affect vascular endothelial cells causing thrombogenesis.
authors.affiliation: Second Department of Internal Medicine, Mie University School of Medicine, Tsu-city, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Wakita
authors.forename: H
authors.initials: H
authors.lastname: Wada
authors.forename: T
authors.initials: T
authors.lastname: Nakase
authors.forename: T
authors.initials: T
authors.lastname: Nakasaki
authors.forename: M
authors.initials: M
authors.lastname: Shimura
authors.forename: K
authors.initials: K
authors.lastname: Hiyoyama
authors.forename: Y
authors.initials: Y
authors.lastname: Mori
authors.forename: E C
authors.initials: EC
authors.lastname: Gabazza
authors.forename: M
authors.initials: M
authors.lastname: Nishikawa
authors.forename: K
authors.initials: K
authors.lastname: Deguchi
authors.forename: H
authors.initials: H
authors.lastname: Shiku
mesh_terms: D000328:Adult; D000925:Anticoagulants / Q000097:blood / Q000276:immunology; D000933:Antifibrinolytic Agents / Q000378:metabolism; D000941:Antigens / Q000097:blood; D000990:Antithrombin III / Q000378:metabolism; D018929:Cell Culture Techniques; D002470:Cell Survival; D015331:Cohort Studies; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D065427:Factor Xa Inhibitors; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D005341:Fibrinolysin / Q000378:metabolism; D005343:Fibrinolytic Agents / Q000097:blood / Q000276:immunology; D006490:Hemostatics; D006801:Humans; D008074:Lipoproteins / Q000097:blood / Q000276:immunology; D016682:Lupus Coagulation Inhibitor / Q000097:blood*; D008180:Lupus Erythematosus, Systemic / Q000097:blood; D008297:Male; D008875:Middle Aged; D010447:Peptide Hydrolases / Q000378:metabolism; D015842:Serine Proteinase Inhibitors / Q000097:blood / Q000276:immunology; D013925:Thromboplastin / Q000096:biosynthesis* / Q000276:immunology / Q000378:metabolism*; D013927:Thrombosis / Q000097:blood / Q000378:metabolism; D014471:Umbilical Veins / Q000473:pathology; D000979:alpha-2-Antiplasmin
chemical_list: D000925:Anticoagulants; D000933:Antifibrinolytic Agents; D000941:Antigens; D065427:Factor Xa Inhibitors; D005338:Fibrin Fibrinogen Degradation Products; D005343:Fibrinolytic Agents; D006490:Hemostatics; D008074:Lipoproteins; D016682:Lupus Coagulation Inhibitor; D015842:Serine Proteinase Inhibitors; D000979:alpha-2-Antiplasmin; C046193:antithrombin III-protease complex; C036309:fibrin fragment D; C051928:lipoprotein-associated coagulation inhibitor; C037742:plasmin-plasmin inhibitor complex; D000990:Antithrombin III; D013925:Thromboplastin; D010447:Peptide Hydrolases; D005341:Fibrinolysin