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Hamostaseologie 2001; 21(02): 44-49
DOI: 10.1055/s-0037-1619504
Original article
Schattauer GmbH

Mechanism of action of Lupus anticoagulants

Aktivierungsmechanismen von Lupus-Antikoagulanzien
J. Arnout
1   Center for Molecular and Vascular Biology, University of Leuven, Belgium
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Publication Date:
27 December 2017 (online)

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Summary

The antiphospholipid syndrome (APS) is defined as the association of antiphospholipid antibodies (aPL) with thrombosis, fetal loss or thrombocytopenia. Some aPL can be detected via coagulation assays where they present as an aspecific inhibitor termed the lupus anticoagulant (LA). Others can be measured via direct binding to cardiolipin and are termed anticardiolipin antibodies. aPL found in APS patients bind to a variety of PL-binding proteins such as beta-2-glycoprotein I (β2GPI) and prothrombin bound to PL surfaces. LA retard coagulation reactions in vitro by forming stable bivalent immune complexes on coagulation active phospholipids. These complexes have increased affinity for PL and compete with coagulation factors for the same catalytic surface. Animal experimental work has provided evidence that aPL are pathogenic. Based on similarities with heparin induced thrombocytopenia, another thrombotic syndrome, the following mechanism might be proposed. As a consequence of an initial activation, anionic PL exposed on bloodcells, endothelium or trophoblasts may promote the formation of bivalent complexes of aPL and PL-binding proteins. In this way, aPL concentrate on the cell surface, activate cellular FcγRII receptors or the complement system and induce thrombosis.

Zusammenfassung

Das Antiphospholipid-Syndrom (APS) ist durch das gemeinsame Auftreten von Antiphospholipid-Antikörpern (APL-AK) mit Thrombosen, Schwangerschaftsverlusten oder einer Thrombozytopenie definiert. Einige APL-AK lassen sich über Phospholipid-(PL-)abhängige Gerinnungstests bestimmen, in denen sie sich als unspezifischer Inhibitor darstellen, den sog. Lupus-Antikoagulans (LA). Andere werden durch ihre direkte Bindung an Cardiolipin bestimmt und als Antikardiolipin-Antikörper (ACA) bezeichnet. APL-AK von APS-Patienten binden gegen eine Vielzahl unterschiedlicher PL-Bindungsproteine wie dem Beta-2-Glykoprotein I (β2GPI) und Prothrombin, gebunden PL-Oberflächen. LA bewirkt in vitro über die Bildung stabiler bivalenter Antigen-Antikörper-Komplexe mit gerinnungsaktiven Phospholipiden eine Verzögerung von Gerinnungsreaktionen. Diese Komplexe haben eine erhöhte Affinität für PL und konkurrieren mit Gerinnungsfaktoren um die gleiche katalytische Oberfläche. Tierexperimente haben den überzeugenden Nachweis für die Pathogenität der APL-AK geliefert. Angesichts der Ähnlichkeiten zur Heparin-induzierten Thrombozytopenie, einem thrombolytischen Syndrom, wäre der folgende Mechanismus denkbar. Als Folge einer initialen Aktivierung könnten anionische Phospholipide freigelegt auf Blutzellen, des Endothels oder des Trophoblasts die Bildung bivalenter Komplexe aus APL-AK und PL-Bindungsproteinen fördern. Auf diese Weise könnten sich bestimmte APL-AK auf der Zelloberfläche anreichern, zelluläre FcγRII-Rezeptoren oder das Komplementsystem aktivieren und Thrombose verursachen.

Keywords

Antiphospholipid syndrome - lupus anticoagulant - beta-2-glycoprotein I - prothrombin

Schlüsselwörter

Antiphospholipid-Syndrome - Lupus-Antikoagulans - Beta-2-Glykoprotein I - Prothrombin
 

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