Skip to main content

Advertisement

SpringerLink
Log in

Predictors of Pregnancy Outcome in Antiphospholipid Syndrome: A Review

  • Published:
Clinical Reviews in Allergy & Immunology Aims and scope Submit manuscript

Abstract

In pregnant women, antiphospholipid syndrome (APS) is associated with an increased risk of preeclampsia, fetal intrauterine growth restriction, and other complications related to uteroplacental insufficiency. In the last two decades, several studies were performed to identify the predictive role of some parameters in relation to obstetric outcome in APS patients. Among these, the uterine velocimetry Doppler is the most studied. It provides a non-invasive method for the study of uteroplacental blood flow, being able to detect a condition of impaired placental perfusion, due to the presence of circulating antiphospholipid antibodies (aPL). To date, the uterine artery Doppler velocimetry resulted to be a useful tool to identify APS pregnancies at higher risk of adverse pregnancy outcome. False-positive IgM for toxoplasmosis, others, rubella, cytomegalovirus, herpes viruses (TORCH) complex is associated to a worse pregnancy outcome because it reflects a dysregulation of the immune system which may amplify placental autoimmune damage. Moreover low levels of complement components are related to an increased incidence of obstetrical complications, suggesting that placental deposition of immune complexes and activation of complement cascade may contribute to placental failure APS related. The abnormal uterine Doppler velocimetry, false-positive TORCH IgM and low levels of complement components can be considered prognostic indexes of poor pregnancy outcome in APS.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Wilson WA (2001) Classification criteria for antiphospholipid syndrome. Rheum Dis Clin North Am 27:499–505

    Article  CAS  PubMed  Google Scholar 

  2. Backos M, Rai R, Baxter N et al (1999) Pregnancy complications in women with recurrent miscarriage associated with antiphospholipid antibodies treated with low dose aspirin and heparin. Br J Obstet Gynaecol 106:102–107

    CAS  PubMed  Google Scholar 

  3. De Wolf F, Carreras LO, Moerna P et al (1982) Decidual vasculopathy an extensive placental infarction in a patient with repeated thromboembolic accidents, recurrent fetal loss and a lupus anticoagulant. Am J Obstet Gynecol 142:829–834

    PubMed  Google Scholar 

  4. Branch DW (2004) Antiphospholipid syndrome and fetal compromise. Thromb Res 114:415–418

    Article  CAS  PubMed  Google Scholar 

  5. Rand JH et al (1997) Antiphospholipid immunoglobulin G antibodies reduce annexin-V levels on syncytiotrophoblast apical membranes and in culture media of placental villi. Am J Obstet Gynecol 177:918–923

    Article  CAS  PubMed  Google Scholar 

  6. Chamley LW, Duncalf AM, Mitchell MD et al (1998) Action of anticardiolipin and antibodies to beta2-glycoprotein-I on trophoblast proliferation as a mechanism for fetal death. Lancet 352:1037–1037

    Article  CAS  PubMed  Google Scholar 

  7. Lyden TW, Vogt E et al (1992) Monoclonal antiphospholipid antibody reactivity against human placental trophoblast. J Reprod Immunol 22:1–14

    Article  CAS  PubMed  Google Scholar 

  8. Sebire NJ, Fox H, Backos M et al (2002) Defective endovascular trophoblast invasion in primary antiphospholipid antibody syndrome-associated early pregnancy failure. Hum Reprod 17:1067–1071

    Article  CAS  PubMed  Google Scholar 

  9. Carbillon L, Uzan M (2000) Pregnancy, vascular tone, and maternal hemodynamics: a crucial adaptation. Obstet Gynecol Surv 55:574–581

    Article  CAS  PubMed  Google Scholar 

  10. Carbillon L, Challier JC, Alouini S et al (2001) Uteroplacental circulation development: Doppler assessment and clinical importance. Placenta 22:795–799

    Article  CAS  PubMed  Google Scholar 

  11. Blumenfeld Z, Weiner Z, Lorber M et al (1991) Anticardiolipin antibodies in patients with recurrent pregnancy wastage: treatment and uterine blood flow. Obstet Gynecol 78:584–589

    CAS  PubMed  Google Scholar 

  12. Bar J, Mashiah R, Cohen-Sacher B et al (2001) Effect of thromboprophylaxis on uterine and fetal circulation in pregnant women with a history of pregnancy complications. Thromb Res 101:235–241

    Article  CAS  PubMed  Google Scholar 

  13. Benifla JL, Tchobroutsky C, Uzan M et al (1992) Predictive value of uterine artery velocity waveforms in pregnancies complicated by systemic lupus erythematosus and antiphospholipid syndrome. Fetal Diagn Ther 7:195–202

    Article  CAS  PubMed  Google Scholar 

  14. Caruso A, De Carolis S, Ferrazzani S et al (1993) Pregnancy outcome in relation to uterine artery flow velocity waveforms and clinical characteristics in women with antiphospholipid syndrome. Obstet Gynecol 82:970–977

    CAS  PubMed  Google Scholar 

  15. Farrell T, Dawson T (2001) Can uterine artery Doppler velocimetry predict adverse pregnancy outcome in women with antiphospholipid syndrome? Acta Obstet Gynecol Scand 80:609–610

    Article  CAS  PubMed  Google Scholar 

  16. Venkat-Raman N, Backos M, Teoh TG et al (2001) Uterine artery Doppler in predicting pregnancy outcome in women with antiphospholipid syndrome. Obstet Gynecol 98:235–242

    Article  CAS  PubMed  Google Scholar 

  17. Le Thi Huong D, Wechsler B, Vauthier-Brouzes D et al (2006) The second trimester Doppler ultrasound examination is the best predictor of late pregnancy outcome in systemic lupus erythematosus and/or the antiphospholipid syndrome. Rheumatology 45:332–338

    Article  PubMed  Google Scholar 

  18. Bats AS, Lejeune V, Cynober E et al (2004) Antiphospholipid syndrome and second- or third-trimester fetal death: follow-up in the next pregnancy. Eur J Obstet Gynecol Reprod Biol 114:125–129

    Article  PubMed  Google Scholar 

  19. Denmanam AM (2000) Systemic lupus erythematosus—is a viral aetiology a credible hypothesis? J Infect 40:229–233

    Article  Google Scholar 

  20. James JA, Neas BR, Moser KL et al (2001) Systemic lupus erythematosus in adults is associated with previous Epstein–Barr virus exposure. Arthritis Rheum 44:1122–1126

    Article  CAS  PubMed  Google Scholar 

  21. Nawata M, Seta N, Yamada M, Sekigawa I, Iida N, Hashimoto H (2001) Possible triggering effect of cytomegalovirus infection on systemic lupus erythematosus. Scand J Rheumatol 30:360–362

    Article  CAS  PubMed  Google Scholar 

  22. Borg EJT, Hoarst G, Hummel E, Limburg PC, Kallenberg CGM (1991) Rises in anti-double stranded DNA antibody levels prior to exacerbations of systemic lupus erythematosus are not merely due to polyclonal B cell activation. Clin Immunol Immunopathol 59:117–128

    Article  PubMed  Google Scholar 

  23. Haserick JR, Long R (1952) Systemic lupus erythematosus preceded by false-positive serologic tests for syphilis: presentation of five cases. Ann Intern Med 37(3):559–565

    CAS  PubMed  Google Scholar 

  24. Miendje Deyi Y, Goubau P, Bodéus M (2000) False-positive IgM antibody tests for Cytomegalovirus in patients with acute Epstein–Barr Virus infection. Eur J Clin Microbiol Infect Dis 19:557–560

    Article  CAS  PubMed  Google Scholar 

  25. Rothfield NF, Evans AS, Niederman JC (1973) Clinical and laboratory aspects of raised virus antibody titers in systemic lupus erythematosus. Ann Rheum Dis 32:238–246

    Article  CAS  PubMed  Google Scholar 

  26. Cannavan FPS (1998) False positive IgM antibody tests for human cytomegalovirus (HCMV) in patients with SLE. Lupus 7:61–62

    Article  CAS  PubMed  Google Scholar 

  27. Stratta P, Colla L, Santi S, Grill A, Besso L, Godio L et al (2002) IgM antibodies against cytomegalovirus in SLE nephritis: viral infection or aspecific autoantibody? J Nephrol 15(1):88–92

    PubMed  Google Scholar 

  28. Moler E, Strom H, Al-Balaghi S (1980) Role of polyclonal activation in specific immune responses. Relevance for findings of antibody activity in various diseases. Scand J Immunol 12:177–182

    Article  Google Scholar 

  29. Rasmussen L, Keisali D, Nelson R, Carney W, Hirsch M, Preiksaitis J et al (1982) Virus-specific IgG and IgM antibodies in normal and immunocompromised subjects infected with cytomegalovirus. J Infect Dis 145:191–199

    CAS  PubMed  Google Scholar 

  30. Su BY, Su CY, Yu SF, Chen CJ (2007) Incidental discovery of high systemic lupus erythematosus disease activity associated with cytomegalovirus viral activity. Med Microbiol Immunol 196:165–170

    Article  PubMed  Google Scholar 

  31. Lau R, Forster GE (1987) False positive results of tests for syphilis and outcome of pregnancy. Br Med J 295(6603):925

    Article  CAS  Google Scholar 

  32. Henriksen R, Sögaard PE, Grennert L, Hansen BU, Manthorpe R, Nilsson I (1989) Autoimmune antibodies and pregnancy outcome in women with false-positive syphilis test results. A retrospective controlled investigation of women from 5170 deliveries. Acta Obstet Gynecol Scand 68(6):537–540

    Article  CAS  PubMed  Google Scholar 

  33. Miyakis S, Lockshin MD, Atsumi T, Branch DW, Brey RL, Cervera R, Derksen RH, DE Groot PG, Koike T, Meroni PL, Reber G, Shoenfeld Y, Tincani A, Vlachoyiannopoulos PG, Krilis SA (2006) J Thromb Haemost 4(2):295–306

    Article  CAS  PubMed  Google Scholar 

  34. Pierangeli SS, Colden-Stanfeield M, Liu X et al (1999) Antiphospholipid antibodies from APS patients activate endothelial cells in vitro and in vivo. Circulation 99:1997–2000

    CAS  PubMed  Google Scholar 

  35. Del Papa N, Guidal L, Sala A et al (1997) Endothelial cell target for aPL antibodies. Human polyclonal and monoclonal anti-β2GPI and induce endothelial cell activation. Arthritis Rheum 40:551–561

    Article  PubMed  Google Scholar 

  36. Zhou H, Woldberg AS, Roubey RA (2004) Characterization of monocyte tissue factor activity induced by IgG aPL and inhibition by dilazep. Blood 104:2353–2358

    Article  CAS  PubMed  Google Scholar 

  37. Holers VM, Girardi G, Mo L et al (2002) C3 activation is required for antiphospholipid antibody-induced fetal loss. J Exp Med 195:211–220

    Article  CAS  PubMed  Google Scholar 

  38. Pierangeli SS, Girardi G, Verga-Ostertag ME et al (2005) Requirement of activation of complement C3 and C5 for antiphospholipid antibody-mediated thrombophilia. Arthritis Rheum 52:2120–2124

    Article  CAS  PubMed  Google Scholar 

  39. Salomon JE, Girardi G (2008) Antiphospholipid antibodies and pregnancy loss: a disorder of inflammation. J Reprod Immunol 77(1):51–56

    Article  Google Scholar 

  40. Shamonki JM, Salomon JE, Hyjek E et al (2007) Excessive complement activation is associated with placental injury in patients with antiphospholipid antibodies. Am J Obstet Gynecol 196(2):167.e1–167.e5

    Article  Google Scholar 

  41. Faulk WP, Jarret R, Keane M et al (1980) Immunological studies of human placentae: complement components in immature and mature chorionic villi. Clin Exp Immunol 40(2):299–305

    CAS  PubMed  Google Scholar 

  42. Tedesco F, Narchi G, Raillo O et al (1993) Susceptibility of human trophoblast to killing by human complement and the role of complement regulatory proteins. J Immunol 151:1562–1570

    CAS  PubMed  Google Scholar 

  43. Girardi G, Redecha P, Salmon JE (2004) Heparin prevents aPL induce fetal loss by inhibiting complement activation. Nat Med 10:1222–1226

    Article  CAS  PubMed  Google Scholar 

  44. Carbone J, Oerra M, Rodriguez-Mahou M et al (1999) Immunological abnormalities in primary APS evolving into SLE: 6 years follow-up in women with repeated pregnancy loss. Lupus 8:274–278

    Article  CAS  PubMed  Google Scholar 

  45. Oku K, Atsumi T, Bohagaki M et al (2008) Complement activation in patients with primary APS. Ann Rheum Dis . doi:10.1136/ard.2008.090670

    PubMed  Google Scholar 

  46. Buyon JP et al (1992) Activation of the alternative complement pathway accompanies disease flares in systemic lupus erythematosus during pregnancy. Arthritis Rheum 35:55–61

    Article  CAS  PubMed  Google Scholar 

  47. Abramson SB, Buyon JP (1992) Activation of the complement pathway: comparison of normal pregnancy, preeclampsia, and systemic lupus erythematosus during pregnancy. Am J Reprod Immunol 28:183–187

    CAS  PubMed  Google Scholar 

  48. Lockshin MD et al (1985) Lupus pregnancy. II. Unusual pattern of hypocomplementemia and thrombocytopenia in the pregnant patient. Arthritis Rheuma 28:58–66

    Article  CAS  Google Scholar 

  49. Buyon JP et al (1986) Serum complement values C3 and C4 to differentiate between systemic lupus activity and pre-eclampsia. Am J Med 81:194–200

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Catholic University of Sacred Hearth, Rome, Italy

    Sara De Carolis, Angela Botta, Stefania Santucci, Serafina Garofalo, Carmelinda Martino, Alessandra Perrelli, Silvia Salvi, Sergio Ferrazzani, Leonardo Caforio & Giovanni Scambia

Authors
  1. Sara De Carolis
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Angela Botta
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Stefania Santucci
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Serafina Garofalo
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Carmelinda Martino
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Alessandra Perrelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Silvia Salvi
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Sergio Ferrazzani
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Leonardo Caforio
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Giovanni Scambia
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sara De Carolis.

Rights and permissions

Reprints and permissions

About this article

Cite this article

De Carolis, S., Botta, A., Santucci, S. et al. Predictors of Pregnancy Outcome in Antiphospholipid Syndrome: A Review. Clinic Rev Allerg Immunol 38, 116–124 (2010). https://doi.org/10.1007/s12016-009-8144-z

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12016-009-8144-z

Keywords

Search

Navigation