Journal of Peking University(Health Sciences) ›› 2018, Vol. 50 ›› Issue (6): 956-961. doi: 10.19723/j.issn.1671-167X.2018.06.003

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Diagnosis and treatment of antiphospholipid antibody:related recurrent spontaneous abortion and analysis of therapeutic drugs and pregnancy outcome in 75 patients with antiphospholipid syndrome

Xin yi LI,Jin xia ZHAO,Xiang yuan LIU()   

  1. Department of Rheumatology and Immunology, Peking University Third Hospital, Beijing 100191, China
  • Received:2018-07-09 Online:2018-12-18 Published:2018-12-17
  • Contact: Xiang yuan LIU E-mail:liu-xiangyuan@263.net

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Abstract:

Recurrent spontaneous abortion is one of the common complications in women of childbearing age during pregnancy. The immune factor accounts for a large proportion of many causes. Antiphospholipid antibody syndrome is the most common type of acquired thrombophilia disease. Autoimmune di-seases that cause thrombosis and obstetric complications under the action of antibodies are also the most common type of immune-related recurrent abortion. At present, there is no unified opinion on the treatment of this disease, especially the treatment of immunoglobulins and other drugs like glucocorticoid. Here we reviewed the progress of diagnosis and treatment of antiphospholipid antibody-related recurrent abortions and retrospectively analyzed and summarized the drug regimens and pregnancy outcomes of this disease with pregnancy patients in our hospital. A total of 75 patients were included. According to their clinical manifestations and laboratory results, these patients were basically divided into two categories:classical antiphospholipid syndrome and non-classical antiphospholipid syndrome. The latter was further divided into serum-negative antiphospholipid syndrome and antiphospholipid antibody-related recurrent abortion patients based on their clinical manifestations and antiphospholipid antibody results. The patients were divided into four categories:aspirin + hydroxychloroquine, aspirin + low molecular weight heparin, aspirin + low molecular weight heparin + hydroxychloroquine, aspirin + hydroxychloroquine + low molecular weight heparin + low dose glucocorticoids. Among them, aspirin + hydroxychloroquine + low molecular weight heparin + low-dose glucocorticoid treatment regimen was most commonly used. Most of the patients who received the above different treatment regimens achieved full-term infants, and a small number of patients had adverse pregnancy outcomes, such as premature delivery, placental abruption, eclampsia, and fetal malformation. And adverse pregnancy outcomes also occurred in this group. It might be related to the severity of the disease and the potential adverse effects of maternal fetal. However, further statistical analysis is needed for the risk factors affecting the pregnancy outcome of this part of patients.

Key words: Recurrent spontaneous abortion, Antibodies, antiphospholipid, Treatment outcome

CLC Number: 

  • R714.21

Table 1

Summary of IVIG for treatment of APS or aPL related RSA"

Author Sample Type study and treatment Dose of IVIG (per month) Outcomes
Wapner, et al[40] 2 Case report, IVIG, aspirin and heparin after RSA on aspirin / prednisone 1 g/kg Full-term infants
Spinnato, et al[41] 5 Uncontrolled case series, IVIG and variable other treatment Total 2 g/kg 5 live-births, 1 preterm at 32 weeks
Dendrinos, et al[42] 78 Randomized trial, IVIG alone vs. LMWH / aspirin 0.4 g/kg Higher live-birth rate in
LMWH / aspirin group
Chay, et al[43] 1 Case report, IVIG after RSA on LDA and LMWH 0.4 g/kg Full-term infants

Table 2

Classical APS and non-classical APS group medication and pregnancy outcomes"

Treatment Classical APS (n=37) Non-classical APS (n=38)
Serum-negative APS aPL related APS
n (%) Outcome n (%) Outcome n (%) Outcome
LDA+LMWH 6 (16.2) Full-term infants (100%) 1 (10) Full-term infants (100%) 8 (28.6) Preterm (12.5%)
LDA+LMWH+
HCQ+GC
20 (54.1) Full-term infants (55%); placental abruption, eclampsia (30%); deformity (10%); preterm (5%) 4 (40) Full-term infants (75%); preterm (25%) 11 (39.3) Full-term infants (100%)
LDA+HCQ 1 (2.7) Full-term infants (100%) 1 (10) Full-term infants (100%) 1 (3.5) Full-term infants (100%)
LDA+LMWH+
HCQ
10 (27.0) Full-term infants (80%);
deformity (20%)
4 (40) Full-term infants (100%) 8 (28.6) Full-term infants (100%)
[1] Bansal AS . Joining the immunological dots in recurrent miscarriage[J]. Am J Reprod Immunol, 2010,64(5):307-315.
doi: 10.1111/j.1600-0897.2010.00864.x pmid: 20528832
[2] Christiansen OB, Nybo Andersen AM, Bosch E , et al. Evidence-based investigations and treatments of recurrent pregnancy loss[J]. Fertil Steril, 2005,83(4):821-839.
doi: 10.1016/j.fertnstert.2004.12.018 pmid: 15820784
[3] Urbanus RT , Derksen RH, de Groot PG. Current insight into diagnostics and pathophysiology of the antiphospolipid syndrome[J]. Blood Rev, 2008,22(2):93-105.
doi: 10.1016/j.blre.2007.09.001 pmid: 17964017
[4] Rai RS, Clifford K, Cohen H , et al. High prospective fetal loss rate in untreated pregnancies of women with recurrent miscarriage and antiphospholipid antibodies[J]. Hum Reprod, 1995,10(12):3301-3304.
doi: 10.1016/0165-0378(96)87779-5 pmid: 8822463
[5] Ruiz-Irastorza G, Crowther M, Branch W , et al. Antiphospholipid syndrome[J]. Lancet, 2010,376(9751):1498-1509.
doi: 10.1016/S0140-6736(10)60709-X
[6] Unlu O, Zuily S, Erkan D . The clinical significance of antiphospholipid antibodies in systemic lupus erythematosus[J]. Eur J Rheumatol, 2016,3(2):75-84.
doi: 10.5152/eurjrheum.2015.0085 pmid: 27708976
[7] Miyakis S, Lockshin MD, Atsumi T , et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS)[J]. J Thromb Haemost, 2006,4(2):295-306.
doi: 10.1111/jth.2006.4.issue-2
[8] Jara LJ, Medina G, Cruz-Cruz P , et al. Non-criteria or seronegative obstetric antiphospholipid syndrome[J]. Isr Med Assoc J, 2017,19(6):382-386.
pmid: 28647939
[9] Loire-Berson P, Mekinian A, Nicaise-Roland P , et al. Outcomes and treatment of obstetrical antiphospholipid syndrome in women with low antiphospholipid antibody levels[J]. J Reprod Immunol, 2012,94(2):222-226.
doi: 10.1016/j.jri.2012.02.004 pmid: 22386067
[10] D’Ippolito S, Meroni PL, Koike T , et al. Obstetric antiphospholipid syndrome: a recent classification for an old defined disorder[J]. Autoimmun Rev, 2014,13(9):901-908.
doi: 10.1016/j.autrev.2014.05.004 pmid: 24820522
[11] Ruffatti A, Calligaro A, Del Ross T , et al. Risk-based secondary prevention of obstetric antiphospholipid syndrome[J]. Lupus, 2012,21(7):741-743.
doi: 10.1177/0961203312446388 pmid: 22635219
[12] Branch DW, Silver RM, Porter TF . Obstetric antiphospholipid syndrome current uncertainties should guide our way[J]. Lupus, 2010,19(4):446-452.
doi: 10.1177/0961203310361490 pmid: 20353986
[13] Arachchillage DR, Machin SJ, Mackie IJ , et al. Diagnosis and management of non-criteria obstetric antiphospholipid syndrome[J]. Thromb Haemost, 2015,113(1):13-19.
doi: 10.1160/TH14-05-0416 pmid: 25318976
[14] Gardiner C, Hills J, Machin SJ , et al. Diagnosis of antiphospholipid syndrome in routine clinical practice[J]. Lupus, 2013,22(1):18-25.
doi: 10.1177/0961203312460722 pmid: 4108293
[15] Alijotas-Reig J, Ferrer-Oliveras R, EUROAPS Study Group . The European Registry on Obstetric Antiphospholipid Syndrome (EUROAPS): a preliminary first year report[J]. Lupus, 2012,21(7):766-768.
doi: 10.1177/0961203312440058 pmid: 22635227
[16] Diejomaoh MF . Recurrent spontaneous miscarriage is still a challenging diagnostic and therapeutic quagmire[J]. Med Princ Pract, 2015,24(Suppl. 1):38-55.
doi: 10.1159/000365973 pmid: 25428171
[17] Dawood F, Farquharson R, Quenby S , et al. Acquired activated protein C resistance may be a risk factor for recurrent fetal loss[J]. Fertil Steril, 2003,80(3):649-650.
doi: 10.1016/S0015-0282(03)00972-5 pmid: 12969717
[18] Rai R, Shlebak A, Cohen H , et al. Factor Ⅴ Leiden and acquired activated protein C resistance among 1 000 women with recurrent miscarriage[J]. Hum Reprod, 2001,16(5):961-965.
doi: 10.1093/humrep/16.5.961 pmid: 11331645
[19] Bremme KA . Haemostatic changes in pregnancy[J]. Best Pract Res Clin Haematol, 2003,16(2):153-168.
doi: 10.1016/S1521-6926(03)00021-5
[20] Redech P, Tilley R, Tencati M , et al. Tissue factor: a link between C5a and neutrophil activation in antiphospholipid antibody induced fetal injury[J]. Blood, 2007,110(7):2423-2431.
doi: 10.1182/blood-2007-01-070631 pmid: 17536017
[21] Esmon C . The interactions between inflammation and coagulation[J]. Br J Haematol, 2005,131(4):417-430.
doi: 10.1016/j.tcm.2005.07.004 pmid: 16226680
[22] Girardi G, Berman J, Redecha P , et al. Complement C5a receptors and neutrophils mediate fetal injury in the antiphospholipid syndrome[J]. J Clin Invest, 2003,112(11):1644-1654.
doi: 10.1172/JCI200318817
[23] Chu AJ . Tissue factor upregulation drives a thrombosis inflammation circuit in relation to cardiovascular complications[J]. Cell Biochem Funct, 2006,24(2):173-192.
doi: 10.1002/cbf.1200 pmid: 15617024
[24] Strukova S . Blood coagulation-dependent inflammation. Coagulation-dependent inflammation and inflammation-dependent thrombosis[J]. Front Biosci, 2006(11):59-80.
doi: 10.2741/1780 pmid: 16146714
[25] Ruf W, Dorfleutner A, Riewald M . Specificity of coagulation factor signaling[J]. J Thromb Haemost, 2003,1(7):1495-1503.
doi: 10.1046/j.1538-7836.2003.00300.x pmid: 12871285
[26] Tulppala M, Marttunen M, Söderstrom-Anttila V , et al. Low-dose aspirin in prevention of miscarriage in women with unexplained or autoimmune related recurrent miscarriage: effect on prostacyclin and thromboxane A2 production[J]. Hum Reprod, 1997,12(7):1567-1572.
doi: 10.1093/humrep/12.7.1567 pmid: 9262298
[27] Pattison NS, Chamley LW, Birdsall M , et al. Does aspirin have a role in improving pregnancy outcome for women with the antiphospholipid syndrome? A randomized controlled trial[J]. Am J Obstet Gynecol, 2000,183(4):1008-1012.
doi: 10.1067/mob.2000.106754 pmid: 11035355
[28] The use of antithrombotics in the prevention of recurrent pregnancy Loss[R]. Royal College of Obstetricians & Gynaecologists, 2011.
[29] Megjugorac NJ, Gallagher GE, Gallagher G . IL-4 enhances IFN-lambda1 (IL-29) production by plasmacytoid DCs via monocyte secretion of IL-1Ra[J]. Blood, 2010,115(21):4185-4190.
doi: 10.1182/blood-2009-09-246157 pmid: 20233967
[30] Laskin CA, Spitzer KA, Clark CA , et al. Low molecular weight heparin and aspirin for recurrent pregnancy loss: results from the randomized, controlled HepASA trial[J]. J Rheumatol, 2009,36(2):279-287.
doi: 10.3899/jrheum.080763) pmid: 19208560
[31] McNamee K, Dawood F, Farquharson RG . Thrombophilia and early pregnancy loss[J]. Best Pract Res Clin Obstet Gynaecol, 2012,26(1):91-102.
doi: 10.1016/j.bpobgyn.2011.10.002 pmid: 22079389
[32] Empson M, Lassere M, Craig J , et al. Prevention of recurrent miscarriage for women with antiphospholipid antibody or lupus anticoagulant [J]. Cochrane Database Syst Rev, 2005(2): CD002859.
doi: 10.1002/14651858.CD002859.pub2 pmid: 15846641
[33] 中华医学会妇产科学分会产科学组. 复发性流产诊治的专家共识[J]. 中华妇产科杂志, 2016,51(1):3-9.
doi: 10.3760/cma.j.issn.0529-567x.2016.01.002
[34] Flint J, Panchal S, Hurrell A , et al. BSR and BHPR guideline on prescribing drugs in pregnancy and breastfeeding. Part I: standard and biologic disease modifying anti-rheumatic drugs and corticosteroids[J]. Rheumatology (Oxford), 2016,55(9):1693-1697.
doi: 10.1093/rheumatology/kev404
[35] Bramham K, Thomas M, Nelson-Piercy C , et al. First-trimester low-dose prednisolone in refractory antiphospholipid antibody-related pregnancy loss[J]. Blood, 2011,117(25):6948-6951.
doi: 10.1182/blood-2011-02-339234 pmid: 21527518
[36] Comarmond C, Cacoub P . Antiphospholipid syndrome: from pa-thogenesis to novel immunomodulatory therapies[J]. Autoimmun Rev, 2013,12(7):752-757.
doi: 10.1016/j.autrev2012.12.006 pmid: 23282546
[37] Wang TF, Lim W . What is the role of hydroxychloroquine in reducing thrombotic risk in patients with antiphospholipid antibo-dies?[J]. Hematology Am Soc Hematol Educ Program, 2016(1):714-716.
doi: 10.1182/asheducation-2016.1.714 pmid: 27913551
[38] Rand JH, Wu XX, Quinn AS , et al. The annexin A5-mediated pathogenic mechanism in the antiphospholipid syndrome: role in pregnancy losses and thrombosis[J]. Lupus, 2010,19(4):460-469.
doi: 10.1177/0961203310361485 pmid: 20353989
[39] de Jesus GR, Rodrigues G, de Jesus NR , et al. Pregnancy morbidity in antiphospholipid syndrome: what is the impact of treatment?[J]. Curr Rheumatol Rep, 2014,16(2):403.
doi: 10.1007/s11926-013-0403-6 pmid: 24390757
[40] Wapner RJ, Cowchock FS, Shapiro SS . Successful treatment in two women with antiphospholipid antibodies and refractory pregnancy losses with intravenous immunoglobulin infusions[J]. Am J Obslel Gynecol, 1989,161(5):1271-1272.
doi: 10.1016/0002-9378(89)90681-9
[41] Spinnato JA, Clark AL, Pierangeli SS , et al. Intravenous immunoglobulin therapy for the antiphospholipid syndrome in pregnancy[J]. Am J Obstet Gynecol, 1995,172(2):690-694.
doi: 10.1016/0002-9378(95)90595-2 pmid: 7856708
[42] Dendrinos S, Sakkas E, Makrakis E . Low-molecular-weight heparin versus intravenous immunoglobulin for recurrent abortion associated with antiphospholipid antibody syndrome[J]. Int J Gynaecol Obstet, 2009,104(3):223-225.
doi: 10.1016/j.ijgo.2008.11.010 pmid: 19116178
[43] Chay J, Lust K, Kubler P , et al. When conventional treatment fails: the role of intravenous immunoglobulin in recurrent pregnancy loss secondary to antiphospholipid syndrome[J]. Obstet Med, 2013,6(2):76-79.
doi: 10.1177/1753495X12472644 pmid: 5052759
[44] Mahadevan U, Wolf DC, Dubinsky M , et al. Placental transfer of anti-tumor necrosis factor agents in pregnant patients with inflammatory bowel disease[J]. Clin Gastroenterol Hepatol, 2013,11(3):286-292.
doi: 10.1016/j.cgh.2012.11.011 pmid: 23200982
[45] Marder W, Littlejohn EA, Somers EC . Pregnancy and autoimmune connective tissue diseases[J]. Best Pract Res Clin Rheumatol, 2016,30(1):63-80.
doi: 10.1016/j.berh.2016.05.002 pmid: 27421217
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