Thromb Haemost 1999; 82(02): 649-655
DOI: 10.1055/s-0037-1615892
Research Article
Schattauer GmbH

Antibody-Mediated Disruption of the Annexin-V Antithrombotic Shield: A New Mechanism for Thrombosis in the Antiphospholipid Syndrome

Jacob H. Rand
1   Department of Medicine, Division of Hematology, The Mount Sinai School of Medicine, NY, USA
,
Xiao-Xuan Wu
1   Department of Medicine, Division of Hematology, The Mount Sinai School of Medicine, NY, USA
› Author Affiliations
Further Information

Publication History

Publication Date:
09 December 2017 (online)

Introduction

The antiphospholipid (aPL) syndrome is a condition that manifests in patients as vascular thromboembolism or recurrent pregnancy loss together with laboratory evidence for the presence of antibodies against anionic phospholipid-protein complexes. For a recent comprehensive review, the reader is referred to Hughes et al.1 The syndrome was first proposed to be a distinct entity, called anticardiolipin syndrome, in 1985,2 and was later renamed antiphospholipid syndrome.3 The disorder was classified as “primary” in the absence of a concurrent autoimmune condition, such as systemic lupus erythematosus, or “secondary” in the presence of another such autoimmune disorder. Antiphospholipid antibodies are detected by their reactivity to anionic phospholipids (or protein-phospholipid complexes) in solid phase immunoassays, or by their inhibition of phospholipid-dependent coagulation reactions, known as the “lupus anticoagulant” effect. The ever-expanding, yet still insufficiently integrated, knowledge of this enigmatic disorder makes this area an intriguing subject for investigation.

The pathophysiologic mechanism of this syndrome has remained obscure, resulting from the apparent multiplicity of antigenic determinants recognized by the antibodies. In addition, a large number of effects1 have been described for the antibodies in vitro and in cell culture systems. These effects, which include the paradoxical lupus anticoagulant (LAC) phenomenon, are a consequence of the numerous roles played by phospholipids in the hemostasis system and in a multitude of biologic processes. The purpose of this review is to introduce the reader to the current state of knowledge of the role of annexin-V in this disorder.

 
  • References

  • 1 Hughes GR. Hughes’ syndrome: the antiphospholipid syndrome. A historical view. Lupus 1998; 7 (Suppl. 02) S1-S4.
  • 2 Hughes GR. The anticardiolipin syndrome. Clin Exp Rheumatol 1985; 3: 285-286.
  • 3 Harris EN, Hughes GRV, Gharavi AE. The antiphospholipid antibody syndrome. J Rheumatol 1987; (Suppl. 13) 210
  • 4 Shapiro SS. The lupus anticoagulant/antiphospholipid syndrome. Annu Rev Med 1996; 47: 533-553.
  • 5 Triplett DA. Lupus anticoagulants/antiphospholipid-protein antibodies: the great imposters. Lupus 1996; 5: 431-435.
  • 6 Shapiro SS, Thiagarajan P. Lupus anticoagulants. Prog Hemost Thromb 1982; 6: 263-285.
  • 7 Ginsberg JS, Wells PS, Brill Edwards P, Donovan D, Moffatt K, Johnston M, Stevens P, Hirsh J. Antiphospholipid antibodies and venous thromboembolism. Blood 1995; 86: 3685-3691.
  • 8 Lockwood CJ, Romero R, Feinberg RF, Clyne LP, Coster B, Hobbins JC. The prevalence and biologic significance of lupus anticoagulant and anticardiolipin antibodies in a general obstetric population. Am J Obstet Gynecol 1989; 161: 369-373.
  • 9 Horbach DA, van Oort E, Donders RC, Derksen RH, de Groot PG. Lupus anticoagulant is the strongest risk factor for both venous and arterial thrombosis in patients with systemic lupus erythe matosus: comparison between different assays for the detection of antiphospholipid antibodies. Thromb Haemost 1996; 76: 916-924.
  • 10 Goldsmith GH, Pierangeli SS, Branch DW, Gharavi AE, Harris EN. Inhibition of prothrombin activation by antiphospholipid antibodies and beta 2-glycoprotein 1. Br J Haematol 1994; 87: 548-554.
  • 11 Roubey RA, Pratt CW, Buyon JP, Winfield JB. Lupus anticoagulant activity of autoimmune antiphospholipid antibodies is dependent upon beta 2-glycoprotein I. J Clin Invest 1992; 90: 1100-1104.
  • 12 Galli M, Bevers EM, Comfurius P, Barbui T, Zwaal RF. Effect of antiphospholipid antibodies on procoagulant activity of activated platelets and platelet-derived microvesicles. Br J Haematol 1993; 83: 466-472.
  • 13 Andree HAM, Hermens WT, Hemker HC, Willems GM. Displacement of factor Va by annexin V. In: Andree HAM. ed. Phospholipid Binding and Anticoagulant Action of Annexin V.. Maastricht, The Netherlands: Universitaire Pers Maastricht; 1992: 73-85.
  • 14 Tait JF, Sakata M, McMullen BA, Miao CH, Funakoshi T, Hendrickson LE, Fujikawa K. Placental anticoagulant proteins: isolation and comparative characterization four members of the lipocortin family. Biochemistry 1988; 27: 6268-6276.
  • 15 Reutelingsperger CP, Kop JM, Hornstra G, Hemker HC. Purification and characterization of a novel protein from bovine aorta that inhibits coagulation: inhibition of the phospholipid-dependent factor Xa-catalyzed prothrombin activation, through a high-affinity binding of the anticoagulant to the phospholipids. Eur J Biochem 1988; 173: 171-178.
  • 16 Moss SE. Ed. The Annexins. Portland Press; London and Chapel Hill: 1992
  • 17 Morgan RO, Fernandez MP. Molecular phylogeny of annexins and identification of a primitive homologue in Giardia lamblia. Mol Biol Evol 1995; 12: 967-979.
  • 18 Morgan RO, Pilar Fernandez M. Distinct annexin subfamilies in plants and protists diverged prior to animal annexins and from a common ancestor. J Mol Evol 1997; 44: 178-188.
  • 19 Menell JS, Cesarman GM, Jacovina AT, McLaughlin MA, Lev EA, Hajjar KA. Annexin II and bleeding in acute promyelocytic leukemia. N Engl J Med 1999; 340: 994-1004.
  • 20 Rand JH. The annexinopathies: a new class of diseases. N Engl J Med 1999; 340: 1035-1036.
  • 21 Lyden TW, Vogt E, Ng AK, Johnson PM, Rote NS. Monoclonal antiphospholipid antibody reactivity against human placental trophoblast. J Reprod Immunol 1992; 22: 1-14.
  • 22 Krikun G, Lockwood CJ, Wu XX, Zhou XD, Guller S, Calandri C, Guha A, Nemerson Y, Rand JH. The expression of the placental anticoagulant protein, annexin V, by villous trophoblasts: immunolocalization and in vitro regulation. Placenta 1994; 15: 601-612.
  • 23 Vogt E, Ng AK, Rote NS. Antiphosphatidylserine antibody removes annexin-V and facilitates the binding of prothrombin at the surface of a choriocarcinoma model of trophoblast differentiation. Am J Obstet Gynecol 1997; 177: 964-972.
  • 24 Thiagarajan P, Tait JF. Binding of annexin V/placental anticoagulant protein I to platelets: evidence for phosphatidylserine exposure in the procoagulant response of activated platelets. J Biol Chem 1990; 265: 17420-17423.
  • 25 Rand JH, Wu XX, Andree HAM, Lockwood CJ, Guller S, Scher J, Harpel PC. Pregnancy loss in the antiphospholipid-antibody syndrome: a possible thrombogenic mechanism. N Engl J Med 1997; 337: 154-160.
  • 26 Flaherty MJ, West S, Heimark RL, Fujikawa K, Tait JF. Placental anticoagulant protein-I: measurement in extracellular fluids and cells of the hemostatic system. J Lab Clin Med 1990; 115: 174-181.
  • 27 Rand JH, Wu XX, Guller S, Gil J, Guha A, Scher J, Lockwood CJ. Reduction of annexin-V (placental anticoagulant protein-I) on placental villi of women with antiphospholipid antibodies and recurrent spontaneous abortion. Am J Obstet Gynecol 1994; 171: 1566-1572.
  • 28 Rand JH, Wu XX, Guller S, Scher J, Andree HAM, Lockwood CJ. Antiphospholipid immunoglobulin G antibodies reduce annexin-V levels on syncytiotrophoblast apical membranes and in culture media of placental villi. Am J Obstet Gynecol 1997; 177: 918-923.
  • 29 Rand JH, Wu XX, Andree HAM, Alexander Ross JB, Rosinova E, Gascon-Lema MG, Calandri C, Harpel PC. Antiphospholipid antibodies accelerate plasma coagulation by inhibiting annexin-V binding to phospholipids: a “lupus procoagulant” phenomenon. Blood 1998; 92: 1652-1660.
  • 30 Willems GM, Janssen MP, Pelsers MM, Comfurius P, Galli M, Zwaal RF, Bevers EM. Role of divalency in the high-affinity binding of anticardiolipin antibody-beta 2 glycoprotein I complexes to lipid membranes. Biochemistry 1996; 35: 13833-13842.
  • 31 Arnout J, Wittevrongel C, Vanrusselt M, Hoylaerts M, Vermylen J. Beta-2-glycoprotein I dependent lupus anticoagulants form stable bivalent antibody beta-2-glycoprotein I complexes on phospholipid surfaces. Thromb Haemost 1998; 79: 79-86.
  • 32 Roubey RA, Hoffman M. From antiphospholipid syndrome to antibody-mediated thrombosis. Lancet 1997; 350: 1491-1493.