The effect of low dose aspirin and low molecular weight heparin (enoxaparin) in recurrent pregnancy loss associated with antiphospholipid antibody syndrome
Keywords:aPL, APS, APA, IUGR, LDA, LMWA, RPL
Background: Recurrent miscarriage affects 1–2% of women. Recurrent pregnancy loss (RPL) is the loss of three or more consecutive pregnancies before or during the 20th week of gestation. The most important association between gestational loss and autoimmune phenomena is the presence of antiphospholipid antibodies represented by the lupus anticoagulants and or anticardiolipin antibodies (Antiphospholipid Antibody Syndrome). The antiphospholipid syndrome is an acquired autoimmune. The clinical features are thrombosis (venous, arterial and microvascular) and/or pregnancy complications; the most prominent of which is recurrent abortion.
Methods: Twenty-two selected patients during pregnancy with clinical and/or serological findings of antiphospholipid syndrome had received low dose aspirin (75 mg once daily orally) plus LMWH enoxaparin (40 mg subcutaneously/day).
Results: There are live born in 86% cases compared to abortion (< 20 weeks gestational age) in 14 % cases. From 19 liveborn babies the mother having normotensive in 79% and preeclampsia 21%, 85% babies having normal growth and 15% are IUGR. 36% cases are at term (>37 weeks) and 50% cases are at preterm (<37 week) on which 9%) is spontaneous preterm and 41% is iatrogenic preterm due to preeclampsia, IUGR, PPROM and APH.
Conclusions: Use of low dose aspirin (75mg) and enoxaparin 40 mg subcutaneously daily in patients with RPL due to antiphospholipid syndrome resulted in higher live birth rates. Combination treatment with aspirin and LMWH leads to a high live birth rate among women with recurrent abortion and antiphospholipid antibodies.
Rai RS, Clifford K, Cohen H, Regan L. High prospective fetal loss rate in untreated pregnancies of women with recurrent miscarriage and antiphospholipid antibodies. Hum Reprod. 1995;10(12):3301-4.
Tuthill JI, Khamashta MA. Management of antiphospholipid syndrome. J Autoimmun 2009;33(2):92-8.
Empson M, Lassere M, Craig J, Scott J. Prevention of recurrent miscarriage for women with antiphospholipid antibody or lupus anticoagulant. Cochrane Database Syst Rev. 2005;18(2):CD002859.
Cohen D, Berger SP, Steup-Beekman GM, Bloemenkamp KW, Bajema IM. Diagnosis and management of the antiphospholipid syndrome. BMJ 2010;340:1125-32.
Galarza-Maldonado C, Kourilovitch MR, Pérez-Fernández OM, Gaybor M, Cordero C, Cabrera S et al. Obstetric antiphospholipid syndrome. Autoimmunity Rev. 2012 Feb 29;11(4):288-95.
Miyakis S, Lockshin MD, Atsumi T, Branch DW, Brey RL, Cervera R et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thrombosis Haemostasis. 2006 Feb 1;4(2):295-306.
Baker Jr WF, Bick RL. The clinical spectrum of Antiphospholipid syndrome. Hematol Oncol Clin N Am. 2008;22:35-52.
Hughes GR, Khamashta MA. Seronegative anti phospholipid syndrome. Ann Rheum Dis. 2003;62:1127.
Berg TG. Antiphospholipid antibody syndrome and pregnancy. 2009. Available at http://emedicine.Medscape.Com/article/261691-print.
Bates SM, Greer IA, Hirsh J, Ginsberg JS. Use of antithrombotic agents during pregnancy: the seventh ACCP Conference on antithrombotic and thrombolytic therapy. Chest 2004;126(3 Suppl):627S-44S.
Triolo G, Ferrante A, Ciccia F, Accardo-Palumbo A, Perino A, Castelli A, et al. Randomized study of subcutaneous low molecular weight heparin plus aspirin versus intravenous immunoglobulin in the treatment of recurrent fetal loss associated with antiphospholipid antibodies. Arthritis Rheum. 2003;48(3):728-31.
Dendrinos S, Sakkas E, Makrakis E. Low-molecular-weight heparin versus intravenous immunoglobulin for recurrent abortion associated with antiphospholipid antibody syndrome. Int J Gynecol Obstet. 2009;104(3):223-5.
Stone S, Poston L. Antiphospholipid antibody syndrome in pregnancy: onset to outcome. Foetal Maternal Med Rev. 2004;15:273-97.
Empson M, Lassere M, Craig JC, Scott JR. Recurrent pregnancy loss with antiphospholipid antibody: a systemic review of therapeutic trials. Obstet Gynecol 2002;99:135-44.
Kutteh WH. Antiphospholipid antibody associated recurrent pregnancy loss: treatment with heparin and low dose aspirin is superior to low dose aspirin alone. Am J Obstet Gynecol. 1996;174:1584-9.
Rai R, Cohen H, Dave M, Regan L. Randomised controlled trial of aspirin plus heparin in pregnant women with recurrent miscarriage associated with antiphospholipid antibodies. Br Med J. 1997;314:253-7.
Stephenson MD, Ballem PJ, T sang P, Purkiss S, Houlihan E, Enson MH. Treatment of antiphospholipid antibody syndrome (APS) in pregnancy: a random pilot total comparing low molecular weight Heparin to unfractionated Heparin. J Obstet Gynacol Can. 2004;26:729-34.
Saadia Fawad Dept. of Gynecology, Aero Hospital. Role of antithrombotic therapy for recurrent pregnancy loss due to APS. J Ayub Med Coll Abbottabad. 2010;22(3).
Mo D, Saravelos S, Metwally M, Makris M, Li TC. Treatment of recurrent miscarriage and antiphospholipid syndrome with low-dose enoxaparin and aspirin. Reprod Biomed Online. 2009 Jan 1;19(2):216-20.
Dadhwal V, Sharma AK, Deka D, Gupta B, Mittal S. The obstetric outcome following treatment in a cohort of patients with antiphospholipid antibody syndrome in a tertiary care center. J Postgraduate Med. 2011 Jan 1;57(1):16.
Farquharson RG, Quenby S, Greaves M. Antiphospholipid syndrome in pregnancy: a randomized, controlled trial of treatment. Obstet Gynecol. 2002;100:408-13.
Jeremić K, Pervulov M, Gojnić M, Dukanac J, Ljubić A, Stojnić J. Comparison of two therapeutic protocols in patients with antiphospholipid antibodies and recurrent miscariages. Vojnosanitetski Pregled. 2005;62(6):435-9.
Serrano F, Nogueira I, Borges A, Branco J. Primary antiphospholipid syndrome: pregnancy outcome in a portuguese population. Acta Reumatologica Portuguesa. 2009;34(3):492-7.
Brenner B, Hoffman R, Blumenfeld Z, Weiner Z, Younis JS. Gestational outcome in thrombophilic women with recurrent pregnancy loss treated by enoxaparin. Thrombosis Haemostasis. 2000;83(5):693-7.
Clark P, Walker ID, Langhorne P, Crichton L, Thomson A, Greaves M, et al. Scottish Pregnancy Intervention Study (SPIN) Collaborators. SPIN (Scottish Pregnancy Intervention) study: a multicenter, randomized controlled trial of low-molecular-weight heparin and lowdose aspirin in women with recurrent miscarriage. Blood. 2010;115:4162-7.
Glasnovic M, Bosnjak I, Vcev A, Soldo I, Kosuta M. Antibody profile of pregnant woman with APS and Pregnancy outcome after treatment with LDA and LMWH. Coll Antropl. 2007;31(1):173-7.
Backos M, Rai R, Baxter N, Chilcott IT, Cohen H, Regan L. Pregnancy complications in women with recurrent miscarriage associated with antiphospholipid antibodies treated with low dose aspirin and heparin. BJOG: Int J Obstet Gynecol. 1999 Feb 1;106(2):102-7.
Royal College of Obstetrician and Gynaecologists. The investigation and treatment of recurrent miscarriage (internet), Guideline No 17. London: RCOG Press; 2003 May (cited 2009 Feb 8):13.