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The role of antiphospholipid antibodies in reproductive failure

Published online by Cambridge University Press:  03 June 2009

D Ware Branch*
Affiliation:
University of Utah Health Science Center, Salt Lake City, Utah, USA
Harry H Hatasaka
Affiliation:
University of Utah Health Science Center, Salt Lake City, Utah, USA
*
University of Utah Health Science Center, 50 North Medical Drive, Salt Lake City, Utah 84132, USA. Fax: (801)-585-5146.

Extract

The relationship between antiphospholipid antibodies and the clinical features of placental insufficiency, pre-eclampsia, and fetal loss has emerged as one of the most exciting new observations in obstetrics in the last 15 years. Antiphospholipid syndrome is the only convincing ‘immunologic’ disturbance of pregnancy affecting the fetus other than anti-erythrocyte or antiplatelet alloimmunization disorders, and it is now routine to test patients with fetal loss for the two best characterized antiphospholipid antibodies, lupus anticoagulant and anticardiolipin. Although there is no proven mechanism for fetal loss, treatment of antiphospholipid antibody-positive mothers during pregnancy with heparin improves pregnancy outcome.

Type
Research Article
Copyright
Copyright © Cambridge University Press 1997

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References

1Cowchock, FS, Reece, EA, Balaban, D, Branch, DW, Plouffe, L. Repeated fetal losses associated with antiphospholipid antibodies: a collaborative randomized trial comparing prednisone to low-dose heparin treatment. Am J Obstet Gynecol 1992; 166: 1318–23.CrossRefGoogle ScholarPubMed
2Branch, DW, Silver, RM, Blackwell, JL, Reading, JC, Scott, JR. Outcome of treated pregnancies in women with antiphospholipid syndrome: an update of the Utah experience. Obstet Gynecol 1992; 4: 614–20.Google Scholar
3Kutteh, WH. Antiphospholipid antibody-associated recurrent pregnancy loss: treatment with heparin and low-dose aspirin is superior to low-dose aspirin. Am J Obstet Gynecol 1996; 174: 1584–9.CrossRefGoogle ScholarPubMed
4Rai, R, Cohen, H, Dave, M, Regan, L. Randomised trial of aspirin and aspirin plus heparin in pregnant women with recurrent miscarriage association with phospholipid antibodies. BMJ 1997; 31: 253–7.CrossRefGoogle Scholar
5Exner, T, Sahan, N, Trudinger, B. Separation of anticardiolipin antibodies from lupus anticoagulant on a phospholipid-coated polystyrene column. Biochem Biophys Res Commun 1988; 155: 1001–7.CrossRefGoogle ScholarPubMed
6McNeil, HP, Chesterman, CN, Krillis, SA. Binding specificity of lupus anticoagulants and anticardiolipin antibodies. Thromb Res 1988; 52: 609–19.CrossRefGoogle ScholarPubMed
7Chamley, LW, Pattison, NS, McKay, EJ. Separation of lupus anticoagulant from anticardiolipin antibodies by ion-exchange and gel filtration chromatography. Haemostasis 1991; 21: 25–9.Google ScholarPubMed
8Pierangeli, SS, Harris, EN, Goldsmith, G, Branch, DW, Dean, WL. Are immunoglobulins with lupus anticoagulant activity specific for phospholipids. Br J Haematol 1993; 85: 124–32.CrossRefGoogle ScholarPubMed
9Branch, DW. Immunologic disease and fetal death. Clin Obstet Gynecol 1987; 30: 295311.CrossRefGoogle ScholarPubMed
10Barbui, T, Cortelazzo, S, Galli, M et al. Antiphospholipid antibodies in early repeated abortions: a case-controlled study. Fertil Steril 1988; 50: 589–92.CrossRefGoogle ScholarPubMed
11Petri, M, Golbus, M, Anderson, R, Whiting-O'Keefe, Q, Corash, L, Hellmann, D. Antinuclear antibody, lupus anticoagulant, and anticardiolipin antibody in women with idiopathic habitual abortion: a controlled prospective study of 44 women. Arthritis Rheum 1987; 30: 601–6.CrossRefGoogle ScholarPubMed
12Out, HJ, Bruinse, HW, Christiaens, GCML et al. Prevalence of antiphospholipid antibodies in patients with fetal loss. Ann Rheum Dis 1991; 50: 553–7.CrossRefGoogle ScholarPubMed
13Parazzini, F, Acaia, B, Faden, D, Lovotti, M, Marelli, G, Cortelazzo, S. Antiphospholipid antibodies and recurrent abortion. Obstet Gynecol 1991; 77: 854–8.Google ScholarPubMed
14Parke, AL, Wilson, D, Maier, D. The prevalence of antiphospholipid antibodies in women with recurrent spontaneous abortion, women with successful pregnancies, and women who have never been pregnant. Arthritis Rheum 1991; 34: 1231–5.CrossRefGoogle ScholarPubMed
15Rai, R, Regan, L, Clifford, K et al. Antiphospholipid antibodies and beta 2-glycoprotein-I in 500 women with recurrent miscarriage: results of a comprehensive screening approach. Hum Reprod 1995; 10: 2001–5.CrossRefGoogle ScholarPubMed
16Lockwood, CJ, Romero, R, Feinburg, 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: 369–73.CrossRefGoogle Scholar
17Pattison, NS, Chamley, LW, McKay, EJ, Liggjns, GC, Butler, WS. Antiphospholipid antibodies in pregnancy: prevalence and clinical associations. Br J Obstet Gynaecol 1993; 100: 909–13.CrossRefGoogle ScholarPubMed
18Out, HJ, Bruinse, HW, Christiaens, GCML, van Vliet, M, de Groot, PG, Nieuwenhuis, HK, Derksen, RH. A prospective, controlled multicenter study on the obstetric risks of pregnant women with antiphospholipid antibodies. Am J Obstet Gynecol 1992; 167: 2632.CrossRefGoogle ScholarPubMed
19Lima, F, Khamashta, MA, Buchanan, NMM, Kerslake, S, Hunt, BJ, Hughes, GR. A study of sixty pregnancies in patients with the antiphospholipid syndrome. Clin Exp Rheumatol 1996; 14: 131–6.Google ScholarPubMed
20Lockshin, MD, Druzin, ML, Qamar, T. Prednisone does not prevent fetal death in women with antiphospholipid antibody. Am J Obstet Gynecol 1989; 160: 439–43.CrossRefGoogle Scholar
21Harris, EN, Spinnato, JA. Should anticardiolipin tests be performed in otherwise healthy pregnant women. Am J Obstet Gynecol 1991; 165: 1272–7.CrossRefGoogle ScholarPubMed
22Robinson, RD, Polzin, WJ, Kozakowski, MH et al. The incidence of antiphospholipid antibodies in the obstetric population [Abstract]. Proceedings of the Annual Clinical Meeting of American College of Obstetricians and Gynecologists, 1992.Google Scholar
23Haddow, JE, Rote, NS, Dostal-Johnson, D, Palomaki, GE, Pulkkinen, AJ, Knight, GJ. Lack of an association between late fetal death and antiphospholipid antibody measurements in the second trimester. Am J Obstet Gynecol 1991; 165: 1308–12.CrossRefGoogle ScholarPubMed
24Infante-Rivard, C, David, M, Gauthier, R, Rivard, G-E. Lupus anticoagulants, anticardiolipin antibodies, and fetal loss. A case-controlled study. N Engl J Med 1991; 325: 1063–6.CrossRefGoogle Scholar
25Harris, EN. Syndrome of the black swan. Br J Rheumatol 1986; 26: 324–6.CrossRefGoogle Scholar
26Alarcon-Segovia, D, Deleze, M, Oria, C et al. Antiphospholipid antibodies and the antiphospholipid syndrome in systemic lupus erythematosus. A prospective study of 500 consecutive cases. Medicine 1989; 68: 353–63.CrossRefGoogle Scholar
27Asherson, RA, Khamashta, MA, Ordi-Ros, J et al. The ‘primary’ antiphospholipid syndrome: major clinical and serological features. Medicine 1989; 68: 366–74.CrossRefGoogle ScholarPubMed
28Oshiro, BT, Silver, RM, Scott, JR, Yu, H, Branch, DW. Antiphospholipid antibodies and fetal death. Obstet Gynecol 1996; 87: 489–93.CrossRefGoogle ScholarPubMed
29Branch, DW, Silver, R, Pierangeli, S, Van Leeuwen, I, Harris, EN. Antiphospholipid antibodies other than lupus anticoagulant and anticardiolipin antibodies in women with recurrent pregnancy loss, fertile controls, and antiphospholipid syndrome. Obstet Gynecol 1997; 89: 549–55.Google ScholarPubMed
30Silver, RM, Porter, TF, van Leeuwen, I, Jeng, G, Scott, JR, Branch, DW. Anticardiolipin antibodies: clinical consequences of ‘low titers’. Obstet Gynecol 1996; 87: 494500.CrossRefGoogle ScholarPubMed
31Silver, RM, MacGregor, SN, Sholl, JS, Hobart, JM, Neerhof, MG, Ragin, A. Comparative trial of prednisone plus aspirin versus aspirin alone in the treatment of anticardiolipin antibody-positive obstetric patients. Am J Obstet Gynecl 1993; 169: 1411–17.CrossRefGoogle ScholarPubMed
32Reece, EA, Gabrielli, S, Cullen, MT, Zheng, XZ, Hobbins, JC, Harris, EN. Recurrent adverse pregnancy outcome and antiphospholipid antibodies. Am J Obstet Gynecol 1990; 163: 162–9.CrossRefGoogle ScholarPubMed
33Ordi, J, Barquinero, J, Vilardell, M, Jordana, R, Tolosa, C, Selva, A, Genover, E. Fetal loss treatment in patients with antiphospholipid antibodies. Ann Rheum Dis 1989; 48: 798802.CrossRefGoogle ScholarPubMed
34Rosove, MH, Tabsh, K, Wasserstrum, N, Howard, P, Hahn, BH, Kalunian, KC. Heparin therapy for pregnant women with lupus anticoagulant or anticardiolipin antibodies. Obstet Gynecol 1990; 75: 630–4.Google ScholarPubMed
35Bahar, AM, Kwak, JYH, Beer, AE et al. Antibodies to phospholipids and nuclear antigens in nonpregnant women with unexplained spontaneous abortions. J Reprod Immunol 1993; 24: 213–22.CrossRefGoogle Scholar
36Kwak, JYH, Gilman-Sachs, A, Beaman, KD, Beer, AE. Autoantibodies in women with primary recurrent spontaneous abortion of unknown etiology. J Reprod Immunol 1992; 22: 1531.CrossRefGoogle ScholarPubMed
37Matzner, W, Chong, P, Xu, G, Ching, W. Characterization of antiphospholipid antibodies in women with recurrent spontaneous abortions. J Reprod Med 1994; 39: 2730.Google ScholarPubMed
38Ruiz, JE, Cubillos, J, Mendoza, JC, Espinel, FJ, Kwak, JYH, Beer, AE. Autoantibodies to phospholipids and nuclear antigens in nonpregnant and pregnancy Colombian women with recurrent spontaneous abortions. J Reprod Immunol 1995; 28: 4151.CrossRefGoogle ScholarPubMed
39Lockshin, MD. Antiphospholipid antibody. Babies, blood clots, biology. JAMA 1997; 277: 1549–51.CrossRefGoogle ScholarPubMed
40Qamar, T, Levy, RA, Sammaritano, L, Gharavi, AE, Lockshin, MD. Characteristics of high-titer IgG antiphospholipid antibody in systemic lupus erythematosus patients with and without fetal death. Arthritis Rheum 1990; 33: 501–4.CrossRefGoogle ScholarPubMed
41Gharavi, AE, Harris, EN, Asherson, RA, Hughes, GRV. Anticardiolipin antibodies: isotype distribution and phospholipid specificity. Ann Rheum Dis 1987; 46: 16.CrossRefGoogle ScholarPubMed
42El-Roeiy, A, Myers, SA, Gleicher, N. The prevalence of autoantibodies and lupus anticoagulant in healthy pregnant women. Obstet Gynecol 1990; 75: 390–6.Google ScholarPubMed
43Harris, EN. The second international anticardiolipin standardization workshop/The Kingston anti-phospholipid antibody study (KAPS) group. Am J Clin Pathol 1990; 94: 476–84.CrossRefGoogle ScholarPubMed
44Ober, C, Darrison, T, Harlow, L, Elias, S, Gleicher, N. Autoantibodies and pregnancy history in a healthy population. Am J Obstet Gynecol 1993; 169: 143–7.CrossRefGoogle Scholar
45Aoki, K, Hayashi, Y, Hirao, Y, Yagami, Y. Specific antiphospholipid antibodies as a predictive variable in patients with recurrent pregnancy loss. Am J Reprod Immunol 1993; 29: 82–7.CrossRefGoogle ScholarPubMed
46Yetman, DL, Kutteh, WH. Antiphospholipid antibody panels and recurrent pregnancy loss: prevalence of anticardiolipin antibodies compared with other antiphospholipid antibodies. Fertil Steril 1996; 66: 540–6.CrossRefGoogle ScholarPubMed
47Kwak, JYH, Gilman-Sachs, A, Beaman, KD, Beer, AE. Reproductive outcome in women with recurrent spontaneous abortions of alloimmune and autoimmune causes: preconception versus postconception treatment. Am J Obstet Gynecol 1992; 166: 1787–95.CrossRefGoogle ScholarPubMed
48Galli, M, Comfurius, P, Maassen, C et al. Anticardiolipin antibodies (ACA) directed not to cardiolipin but to a plasma protein cofactor. Lancet 1990; 335: 1544–7.CrossRefGoogle Scholar
49Matsuura, E, Igarashi, Y, Fujimoto, M, Ichikawa, K, Koike, T. Anticardiolipin cofactor(s) and differential diagnosis of autoimmune disease (letter). Lancet 1990; 336: 177–8.CrossRefGoogle ScholarPubMed
50McNeil, HP, Simpson, RJ, Chesterman, CN, Krilis, SA. Anti-phospholipid antibodies are directed against a complex antigen that includes a lipid-binding inhibitor of coagulation: β2-glycoprotein-I (apolipoprotein H). Proc Natl Acad Sci USA 1990; 87: 4120–4.CrossRefGoogle ScholarPubMed
51Aoki, K, Dudkiewicz, AB, Matsuura, E, Novotny, M, Kaberlein, G, Gleicher, N. Clinical significance of B2-glycoprotein I-dependent anticardiolipin antibodies in the reproductive autoimmune failure syndrome: correlation with conventional antiphospholipid antibody detection systems. J Obstet Gynecol 1995; 172: 926–31.CrossRefGoogle Scholar
52Gleicher, N, El-Roeiy, A, Confino, E, Friberg, J. Reproductive failure because of autoantibodies: unexplained infertility and pregnancy wastage. Am J Obstet Gynecol 1989; 160: 1367–85.CrossRefGoogle ScholarPubMed
53Taylor, PV, Campbell, JM, Scott, JS. Presence of autoantibodies in women with unexplained infertility. Am J Obstet Gynecol 1989; 161: 377–9.CrossRefGoogle ScholarPubMed
54Roussev, RG, Kaider, BD, Price, DE, Coulam, CB. Laboratory evaluation of women experiencing reproductive failure. Am J Reprod Immunol 1996; 35: 415–20.CrossRefGoogle ScholarPubMed
55Hatasaka, H, Porter, TF, Silver, RM, Lee, RM, Ricks, C, Branch, DW. Antiphospholipid antibody levels are not elevated among women with tubal factor and unexplained infertility. Fertil Steril 1997; 68 [Suppl]: S18.CrossRefGoogle Scholar
56El-Roeiy, A, Gleicher, N, Friberg, J, Confino, E, Dudkiewicz, A. Correlation between peripheral blood and follicular fluid autoantibodies and impact on in vitro fertilization. Obstet Gynecol 1987; 70: 163–70.Google ScholarPubMed
57Gleicher, N, Liu, HC, Dudkiewicz, A, Rosenwaks, Z, Kaberlein, G, Pratt, D, Kadande, V. Autoantibody profiles and immunoglobulin levels as predictors of in vitro fertilization success. Am J Obstet Gynecol 1994; 170: 1145–9.CrossRefGoogle ScholarPubMed
58Nip, MMC, Taylor, PV, Rutherford, AJ, Hancock, KW. Autoantibodies and antisperm antibodies in sera and follicular fluids of infertile patients; relation to reproductive outcome after in-vitro fertilization. Hum Reprod 1995; 10: 2564–9.CrossRefGoogle ScholarPubMed
59Kowalik, A, Vichnin, M, Liu, H-C, Branch, DW, Berkeley, AS. Mid-follicular anticardiolipin and antiphosphatidylserine antibody titers do not correlate with I VF outcome. Fertil Steril 1997; 68: 298304.CrossRefGoogle Scholar
60Birdsall, MA, Lockwood, GM, Ledger, WL, Johnson, PM, Chamley, LW. Antiphospholipid antibodies in women having in-vitro fertilization. Human Reprod 1996; 11: 1185–9.CrossRefGoogle ScholarPubMed
61Denis, AL, Guido, M, Adler, RD, Bergh, PA, Brenner, C, Scott, RT. Antiphospholipid antibodies and pregnancy rates and outcome in in vitro fertilization patients. Fertil Steril 1997; 67: 1084–90.CrossRefGoogle ScholarPubMed
62Geva, E, Amit, A, Lerner-Geva, L, Azem, F, Yovel, I, Lessing, JB. Autoimmune disorders: another possible cause for in-vitro fertilization and embryo transfer failure. Hum Reprod 1995; 10: 2260–3.CrossRefGoogle ScholarPubMed
63Birkenfeld, A, Mukaida, T, Minichiello, L, Jackson, M, Kase, NG, Yemini, M. Incidence of autoimmune antibodies in failed embryo transfer cycles. Am J Reprod Immunol 1994; 31: 65–8.CrossRefGoogle ScholarPubMed
64Fisch, B, Fried, S, Manor, Y, Ovadia, J, Witz, IP, Yron, I. Increased antiphospholipid antibody activity in in-vitro fertilization patients is not treatment-dependent but rather an inherent characteristic of the infertile state. Am J Reprod Immunol 1995; 34: 370–4.CrossRefGoogle Scholar
65Kutteh, WH, Yetman, DL, Chantilis, SJ, Crain, J. Effect of antiphospholipid antibodies in women undergoing in vitro fertilization: role of heparin and aspirin. Hum Reprod 1997; 12: 1171–5.CrossRefGoogle ScholarPubMed
66Schenk, LM, Butler, L, Morris, JP et al. Heparin and aspirin treatment yields higher implantation rates in IVF patients with antiphospholipid antibody seropositivity compared to untreated seronegative patients [Abstract]. Fertil Steril 1996; 67 [Suppl]: S39.Google Scholar
67Sher, G, Feinman, M, Zouves, C et al. High fecundity rates following antiphospholipid antibody seropositive women treated with heparin and aspirin. Hum Reprod 1994; 9: 2278–93.CrossRefGoogle ScholarPubMed
68Bronson, RA. Immunology and reproductive medicine (editorial). Hum Reprod 1995; 10: 755–7.CrossRefGoogle Scholar
69Brandt, JT, Triplett, DA, Alving, B, Scharrer, I. Criteria for the diagnosis of lupus anticoagulants: an update on behalf of the Subcommittee on Lupus Anticoagulant/Antiphospholipid antibody of the Scientific and Standardization Committee of the ISTH. Thromb Hemost 1996; 74: 1185–90.Google Scholar
70Harris, EN, Pierangeli, SS, Birch, D. Anticardiolipin wet workshop report: Vth International Symposium on Antiphospholipid Antibodies. Am J Clin Pathol 1994; 101: 616–24.CrossRefGoogle Scholar
71Peaceman, AM, Silver, RK, MacGregor, N, Socol, ML. Interlaboratory variation in antiphospholipid antibody testing. Am J Obstet Gynecol 1992; 166: 1780–7.CrossRefGoogle ScholarPubMed
72Kandiah, DA, Sheng, YH, Krilis, SA. β2-glycoprotein I: target antigen for autoantibodies in ‘antiphospholipid syndrome’. Lupus 1996; 5: 381–5.CrossRefGoogle ScholarPubMed
73Hörrkö, S, Miller, E, Dudl, E et al. Antiphospholipid antibodies are directed against epitopes of oxidized phospholipids. Recognition of cardiolipin by monoclonal antibodies to epitopes of oxidized low density lipoprotein. J Clin Invest 1996; 98: 815–25.CrossRefGoogle Scholar
74Hörrkö, S, Miller, E, Branch, DW, Palinski, W, Witztum, JL. The epitopes for some antiphospholipid antibodies are adducts of oxidized phospholipid and β2-glycoprotein I (and other proteins). Proc Natl Acad Sci 1997 (submitted).CrossRefGoogle Scholar