Novel considerations in the pathogenesis of the antiphospholipid syndrome: involvement of the tissue factor pathway of blood coagulation.

School of Human Life Sciences, University of Tasmania, Tasmania, Australia.
Seminars in Thrombosis and Hemostasis (Impact Factor: 4.22). 05/2008; 34(3):251-5. DOI: 10.1055/s-0028-1082268
Source: PubMed

ABSTRACT The antiphospholipid syndrome (APS) is characterized by clinical manifestations such as venous and arterial thrombosis, thrombocytopenia and/or recurrent pregnancy loss, as well as the persistent presence of laboratory markers of antiphospholipid (aPL) antibodies detected in laboratory assays. Though it is generally accepted that aPL antibodies, such as anticardiolipin (aCL), anti-beta2 glycoprotein I (anti-beta2GPI), and lupus anticoagulants (LA) contribute to the pathogenesis of APS, precise mechanism(s) are yet to be fully described. It is probable that aPL antibodies bind to a range of cellular targets (e.g., platelets, endothelial cells, and monocytes), leading to thrombosis and obstetric complications. There is now increasing evidence that alterations to the tissue factor (TF) pathway of blood coagulation contribute toward hypercoagulability in patients with aPL antibodies. This article reviews current evidence that suggests changes and/or interference to the major pathway of blood coagulation may represent a novel mechanism that contributes to the development of APS.

1 Bookmark
  • [Show abstract] [Hide abstract]
    ABSTRACT: Increased mean platelet volume (MPV) is associated with platelet reactivity and is a predictor of cardiovascular risk and unprovoked venous thromboembolism. The aim of our study was to evaluate MPV in patients with confirmed antiphospholipid antibody syndrome (APS) and to identify the correlation between the value of MPV and the recurrence of thrombosis. The studied group consists of 247 patients with a history of thrombosis and/or pregnancy loss (median age 38, range 18-66 years) classified as APS group (n = 70) or APS negative patients (n = 177) according to the updated Sapporo criteria. The control group consisted of 98 healthy subjects. MPV was significantly higher in the group of patients with clinically and laboratory confirmed APS (median 7.85, range 4.73-12.2 fl) in comparison with the controls. It was also higher than in APS negative patients (7.61, range 5.21-12.3 fl). APS patients with triple positivity for antiphospholipid antibodies with respect to Miyakis classification categories had higher MPV values than other APS patients (9.69 ± 1.85 vs. 7.29 ± 1.3 fl, p = 0.001). Recurrent thrombotic episodes were observed in 83 patients, but among the triple positive high-risk patients with APS in 80 % cases (p = 0.0046). In receiver operating characteristic curve analysis, the value of MPV level for thrombosis recurrence prediction in the APS group with sensitivity of 86 % and specificity of 82 % was 7.4 fl. In the multivariate logistic regression model, MPV above 7.4 fl (OR 3.65; 95 % CI 1.38-9.64, p = 0.009) significantly predicts thrombosis recurrence. Our results identify the value of MPV as a prognostic factor of thrombosis recurrence in patients with APS.
    Rheumatology International 03/2014; · 2.21 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Recurrent early miscarriages (excluding chromosomal anomalies), late fetal loss, and maternal thrombosis are characteristic of obstetric antiphospholipid syndrome (APS). Obstetric complications such as preeclampsia, fetal growth restriction, premature delivery, and fetal death also occur in higher frequency in APS patients than in the general population. A high-risk obstetric center is needed for proper evaluation of and intervention with pregnant women with APS. Association with lupus carries additional risk of thrombosis when antiphospholipid antibodies (aPLs) are present. Gestational results with live births are improved to about 80% when antithrombotic therapy is used, but failure in 20% to 30% of the cases despite correct treatment with low-dose aspirin with or without heparin reveals new pathways for pregnancy loss in APS and unmet needs. At the moment, there is no recommendation to investigate patients with infertility for the presence of aPLs.
    Current Rheumatology Reports 11/2011; 14(1):79-86.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Thrombosis is a frequent manifestation in patients with systemic lupus erythematosus (SLE), although precise mechanisms remain unclear. This study investigated whether the major physiological trigger of blood coagulation, the tissue factor (TF) pathway, was altered in SLE patients. Furthermore, we investigated potential associations between the TF pathway, the presence of antiphospholipid (APL) antibodies and other abnormalities present in SLE. A total of 101 participants (40 SLE patients and 61 age- and sex-matched controls) were recruited from Tasmania, Australia. Markers of the TF pathway, hypercoagulability, inflammation and endothelial cell damage were measured in plasma. Serum levels of APL antibodies (anti-cardiolipin antibodies [ACL], lupus anticoagulants [LAC], anti-beta2-glycoprotein-1 [anti-β2GP1] and anti-prothrombin antibodies) were also determined. Despite similar TF and TF pathway inhibitor (TFPI) total antigen levels, SLE patients had significantly increased levels of TFPI free antigen (patients vs controls; mean ± SD) (11.6 ± 0.9 ng/mL vs 6.4 ± 0.4 ng/mL; p < 0.001) but significantly reduced TFPI activity (0.66  ± 0.07 U/mL vs 1.22 ± 0.03 U/mL; p < 0.001), compared with healthy controls. Anti-TFPI activity, designated as the ability of isolated IgG fractions to inhibit TFPI activity in normal plasma, was detected in 19/40 (47.5%) of SLE patients and 3/40 (7.5%) of healthy controls. The significant reduction in TFPI activity in SLE patients reflects impaired functional control of the TF pathway. Moreover, SLE patients with a history of thrombosis demonstrated higher levels of TFPI activity compared with patients without a previous thrombotic event (0.97 ± 0.07 U/mL vs 0.53 ± 0.14 U/mL; p = 0.0026). Changes to the TF pathway were not associated with manifestations of SLE such as inflammation or endothelial cell damage. The results from this study suggest hypercoagulability in SLE may (in part) be due to reduced TFPI activity, a mechanism that appears to be independent of other abnormalities in SLE.
    Lupus 12/2011; 20(14):1474-83. · 2.78 Impact Factor


Available from