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: 3.88). 05/2008; 34(3):251-5. DOI: 10.1055/s-0028-1082268
Source: PubMed


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.

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    ABSTRACT: Almost 30 years after it was first described as a discrete clinical entity, the antiphospholipid syndrome (APS) remains a challenge for clinicians in a wide range of specialities. There remain ongoing issues regarding nomenclature, the expanding range of clinical manifestations, and management of certain APS patient subgroups. In addition to the presence of appropriate clinical features, the diagnosis of APS also fundamentally requires the finding of positive antiphospholipid antibody test result(s), and unfortunately much still has to be done to improve the robustness, reproducibility, and standardization of these assays. This article discusses ongoing dilemmas and issues related to clinical aspects of APS including (i) the derivation of the current nomenclature and the implications of recent proposals for its revision; (ii) the problems that the protean clinical manifestations pose for many clinicians, in particular those not intimately familiar with APS; (iii) the potential pitfalls of applying the APS classification criteria as diagnostic criteria (although no doubt tempting for nonspecialist clinicians); (iv) the concept of seronegative APS and the effect that recent proposed changes in antiphospholipid antibody testing strategies may have on this diagnosis; and finally (v) an overview of key developments in the clinical management of APS patients over the past 30 years.
    Seminars in Thrombosis and Hemostasis 05/2008; 34(3):295-304. DOI:10.1055/s-0028-1082275 · 3.88 Impact Factor
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    ABSTRACT: Extensive research work over the past couple of decades has indicated a series of intricate relations between immune and reproductive systems. A range of reproductive immunology topics including the roles of adoptive and innate immunity in infertility and pregnancy, the immune system's role in induction of labor and preterm delivery, and immuno-modulatory effects of the female sex hormones will be discussed in this and the next issue of the Journal. The implications of this research on the development of novel therapeutic approaches are also addressed.
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    ABSTRACT: Tissue factor (TF) is an initiator of the extrinsic blood coagulation, which is often susceptible to upregulation by tissue injury, advanced glycation end-product, or diverse inflammation. TF hypercoagulability is accompanied by elevated generation of clotting factors (e.g., FVIIa, FXa, and thrombin) and fibrin production, all of which are proinflammatory. In this laboratory, our in vitro experimental results show that polycationic anticoagulants (compound 48/80, ruthenium red, polybrene, protamine, Buforin I, and cationic polyamino acids) intervene TF hypercoagulability at posttranslational level. Polycations preferentially suppress TF-dependent FVII activation with diminished FVIIa formation shown on Western blotting, resulting in non- or un-competitive inhibition on FVIIa amidolytic activity. In contrast, polycations have no effect on FVIIa catalysis, FXa activity, or thrombin activity per se. Polycations could present a new class of anticoagulants with such unique upstream downregulation of blood coagulation. In view of coagulation-dependent inflammation and the new paradigm of blood coagulation-inflammation-thrombosis circuit, the polycations as a new class of anticoagulants could effectively contribute to antiinflammation, antithrombosis, and cardioprotection. Further development of effective anticoagulants is of biopharmaceutical significance in broadly easing disease conditions.
    02/2011; 10(1):13-8. DOI:10.2174/187152811794352079
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