Abstract
Inflammation and immune activation have been associated with thrombosis in a number of settings. We have been interested in the question of how the presence of a type of autoantibody, so-called “antiphospholipid” antibody, leads to thrombosis. Several mechanisms have been proposed including modulation of tissue factor expression, enhancement of procoagulant binding to platelets, and interference with antithrombotic mechanisms. We developed a cell-based model of coagulation that, unlike current coagulation assays, reflects some of the in vivo activities of “antiphospholipid” antibodies. “Antiphospholipid” antibodies against the phospholipid-binding protein beta-2-glycoprotein-1 enhance thrombin generation in this model system, primarily by enhancing procoagulant reactions on tissue factor-bearing cells.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Galli M, Comfurius P, Maassen C et al.: Anticardiolipin antibodies (ACA) directed not to cardiolipin but to a plasma protein cofactor. Lancet 1990;335:1544–1547.
Roubey RA, Eisenberg RA, Harper MF, Winfield JB: “Anticardiolipin” auto antibodies recognize beta 2-glycoprotein 1 in the absence of phospholipid. Importance of Ag density and bivalent binding. J Immunol 1995;154:954–960.
Roubey RA: Antiphospholipid syndrome: antibodies and antigens. Curr Opin Hematol, 2000;7: 316–320.
de Groot PG, Oosting JD, Derksen RH: Antiphospholipid antibodies: specificity and pathophysiology. Baillieres Clin Haematol 1993;6: 691–709.
Rand JH, Wu XX, Andree HA, et al.: Antiphospholipid antibodies accelerate plasma coagulation by inhibiting annexin-V binding to phospholipids: a “lupus procoagulant” phenomenon. Blood 1998; 92:1652–1660.
Monroe DM, Roberts HR, Hoffman M: Platelet procoagulant-complex assembly in a tissue factor-initiated system. Br J Haematol 1994;88:364–371.
Hoffman M, Monroe DM, Oliver JA, Roberts HR: Factors 1Xa and Xa play distinct roles in tissue factor-dependent initiation of coagulation. Blood 1995;86: 1794–1801.
Monroe DM, Hoffman M, Roberts HR: Transmission of a procoagulant signal from tissue factor-bearing cells to platelets. Blood Coagul. Fibrinolysis 1996;7: 459–464.
Hoffman M, Monroe DM, Roberts HR: Cellular interactions in hemostasis. Haemostasis 1996;26:12–16.
Roberts H, Monroe D, Oliver J, Chang J, Hoffman M: Newerconcepts of blood coagulation. Haemophilia 1998;4:331–334.
Oliver J, Monroe D, Roberts H, Hoffman M: Thrombin activates factor XI on activated platelets in the absence of factor XII. Arterioscler Thromb Vasc Biol 1999; 19:170–177.
Cuadrado MJ, Lopez-Pedrera C, Khamashta MA, et al.: Thrombosis in primary antiphospholipid syndrome: a pivotal role for monocyte tissue factor expression. Arthritis Rheum 1997;40: 834–841.
Reverter JC, Tassies D, Font J, et al.: Hypercoagulable state in patients with antiphospholipid syndrome is related to high induced tissue factor expression on monocytes and to low free protein S. Arterioscler Thromb Vasc Biol 1996;16:1319–1326.
Martini F, Farsi A, Gori AM, et al.: Antiphospholipid antibodies (aPL) increase the potential monocyte procoagulant activity in patients with systemic lupus erythematosus. Lupus 1996;5:206–211.
Kornberg A, Blank M, Kaufman S, Shoenfeld Y: Induction of tissue factor-like activity in monocytes by anti-cardiolipin antibodies. J Immunol 1994;153:1328–1332.
Nimpf J, Bevers EM, Bomans PH, et al.: Prothrombinase activity of human platelets is inhibited by beta 2-glycoprotein-1. Biochim Biophys Acta 1986;884: 142–149.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Hoffman, M., Monroe, D.M. & Roubey, R.A.S. Links between the immune and coagulation systems: How do “antiphospholipid antibodies” cause thrombosis?. Immunol Res 22, 191–197 (2000). https://doi.org/10.1385/IR:22:2-3:191
Issue Date:
DOI: https://doi.org/10.1385/IR:22:2-3:191