Enoxaparin and aspirin versus aspirin alone therapy for recurrent pregnancy loss due to anti-phospholipid syndrome (APS)

Abstract

Recurrent pregnancy loss (RPL) or habitual miscarriage 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  (APA) represented by the lupus anticoagulants and or anticardiolipin antibodies (Antiphospholipid Antibody Syndrom). The antiphospholipid syndrome (APS) 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. It is important to recognize the syndrome and to institute appropriate therapy to reduce the risk of recurrent pregnancy loss. Many treatment regimens introduced. Today anticoagulants and aspirin treatment is emerging as the treatment of choice for the APA syndrome associated with recurrent pregnancy loss.
Aim of the study
To investigate the efficacy of combined aspirin and low molecular heparin therapy as opposed to aspirin alone in the management of immunological recurrent abortion
Patients and methods
This is a prospective study of 70 female patients presented with recurrent pregnancy loss (RPL) or habitual miscarriage (loss of three or more consecutive pregnancies before the 20th week of gestation) and repeatedly positive test results for anticardiolipin and or lupus anticoagulant. The duration of the study was 3 years (February 2013-February 2016); the cases were presented both to the 
private clinic and the hospital (Al-Batool teaching hospital). The patients were randomly put in two groups. In both groups the patients started receiving treatment as soon as they had a positive result on a pregnancy test.  Group A (47 patients), the women given both low molecular weight heparin (LMW self-administered injection; 4000 IU/day) plus low-dose aspirin (81 mg/day). Group B (23 patients) assigned to receive aspirin alone (81mg/day). From 20th week of gestation, pregnancies were monitored by serial ultrasonography and Doppler studies of the umbilical artery circulation, fetal growth and wellbeing. The husbands were all fertile and had normal sperm parameters.
Results
There was a highly significant difference between Groups A and B in the rate of miscarriages (4 miscarriage in Group A (9%) versus 8 miscarriages in Group B (35%); p = 0.02). Most abortion in the two Groups occurred in the first trimester (3 in Group A and 5 in Group B). In the low-dose aspirin plus LMWH  (Group  A)  there  were a  significantly  greater  number  of  live  births  (43/47(91%)  versus 15/23(65%) in group B; p =0.02).
The mean gestational age and the neonatal birth weight were significantly higher in Group A than in Group B. The mean gestational age at delivery in Group A was 37.86± 1.8 versus 36.13 ±2.39 weeks in Group B; p= 0.005. The mean birth weight in Groups A was 3252 ±459 versus 2907 ± 618 g in Group B; p =0.03. 

Significant difference in the mode of delivery. Nineteen (19) of the 58 women with successful pregnancies (33%) delivered prematurely (<37 weeks’ gestation). Eleven of them were in Group A [6/43 (14%) due to preterm labour, 4/43(9%) due to IUGR, and 1/43(2%) due to pre-eclampsia] and the remaining 8 were in Group B [3/15(20%) due to preterm labour, 3/15(20%) due to IUGR and 2/15 (13%) due to pre-eclampsia]. No woman developed a thromboembolic complication during pregnancy or the puerperium.
Both low dose aspirin and LMWH were well tolerated. Of those taking heparin, none developed thrombocytopenia or had symptomatic complications apart from mild bruising localized to the injection site.
Conclusion
Combination treatment with aspirin and LMWH leads to a high live birth rate among women with recurrent abortion and antiphospholipid antibodies. This combination may promote successful embryonic implantation in  the  early stages  of  pregnancy and  protect  against thrombosis  of  the  uteroplacental vasculature after successful placentation. 
Recommendation
Future studies should be aimed at refining the protocol used in this trial to determine the benefits of preconceptional administration of heparin and whether it can be stopped after 13 weeks of gestation without adversely affecting the rate of live births.
However, successful pregnancies are prone to a high risk of complications during all pregnancy. Close antenatal surveillance and planned delivery of these pregnancies in a unit with specialist obstetric and neonatal intensive care are indicated.