Organization of a Randomized Clinical Trial for the Prevention of Recurrent Thrombosis in the Antiphospholipid Syndrome: the WAPS Project (Warfarin in Antiphospholipid Syndrome)
Antiphospholipid (aPL) antibodies are a heterogeneous family of immunoglobulins directed against different protein-phospholipid complexes [1, 2]. They include lupus anticoagulants (LA) and anticardiolipin antibodies (aCL). The former recognize the (human) prothrombin-phospholipid complex, thereby inhibiting the phospholipid-dependent coagulation reactions , whereas the latter is directed towards β2-glycoprotein I (β2-GPI) bound to an anionic lipid surface [4, 5]. aCL can be divided into two groups [6, 7]: aCL type A, which inhibit coagulation reactions by enhancing the binding of β2-GPI to the procoagulant phospholipid surface; and aCL type B, which are devoid of anticoagulant properties. In recent years, the presence of aPL which recognize lipid-bound Protein S and lipid-bound activated Protein C (aPC) has been reported [8–10]. A consistent finding of many studies is the inhibition by aPL of the inactivation of factor Va by aPC in the presence of Protein S. In this way, aPL can interfere with the physiological function of these natural anticoagulants, suggesting a possible, albeit still unproven, mechanism for their association with thrombotic events [11, 12].
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- 3.Bevers EM, Galli M, Barbui T et al (1991) Lupus anticoagulant IgG’s ( LA) are not directed to phospholipids only, but to a complex of lipid-bound human prothrombin, Thromb Haemostas 66: 629–632Google Scholar
- 4.Galli M, Comfurius P, Maassen C et al (1990) Anticardiolipin antibodies ( ACA) directed not to cardiolipin but to a plasma protein cofactor. Lancet 336: 177–178Google Scholar
- 10.Oosting JD, Derksen RHWM, Bobbink WG et al (1983) Antiphospholipid antibodies directed against a combination of phospholipids with prothrombin, protein C or protein S: an explanation for their pathogenic mechanism? Blood 81: 2618–2625Google Scholar
- 20.Pierangeli SS, Barker JH, Stikovac et al (1994) Effect of human IgG antiphospholipid antibodies on an in vivo thrombosis model in mice. Thromb Haemostas 71: 670–674Google Scholar
- 23.Levine SR, Brey RL, Joseph CLM et al (1992) Risk of recurrent thromboembolic events in patients with focal cerebral ischemia and antiphospholipid antibodies. Stroke 23 (Suppl I): 29–32Google Scholar
- 36.Dalen JE, Hirsh J (1992) Third ACCP Consensus Conference on antithrombotic therapy. Chest (Suppl) 102: 303–538Google Scholar