Trip Answers

Question answered:27/07/07 Warning! this question is over two years old.

The secondary literature reports possible benefit of low dose aspirin and low dose heparin in women who have suffered recurrent miscarriage due to antiphospholipid syndrome. Unfortunately, many of  these sources do not explicitly state whether low dose heparin and low dose aspirin should be prescribed for the population of women who have no history of thromboembolism as well as patients who have a history of thromboembolism.

 

Empson et al’s systematic review on the prevention of recurrent miscarriage for women with antiphospholipid antibody or lupus anticoagulant concludes:

 

“Combined unfractionated heparin and aspirin may reduce pregnancy loss by 54%. Large, randomised controlled trials with adequate allocation concealment are needed to explore potential differences between unfractionated heparin and LMWH.”

 

They add:

 

“[The conclusion is] based on only two small trials and one of these lacked adequate allocation concealment.” [1]

 

The Royal College of Obstetricians and Gynaecologists guideline on recurrent miscarriage states:

 

“In women with a history of recurrent miscarriage and aPL, future live birth rate is significantly improved when a combination therapy of aspirin plus heparin is prescribed.

 

A randomised controlled trial showed that the live birth rate of women with recurrent miscarriage associated with aPL treated with low-dose aspirin only is 40% and this is significantly improved to 70% when they are treated with low-dose aspirin in combination with low-dose heparin.
A meta-analysis of two controlled trials concluded that, in women with a history of recurrent miscarriage associated with aPL, treatment with low-dose heparin plus low-dose aspirin significantly reduced the pregnancy losses by 54% when compared with aspirin alone. However, these trials do not exclude the possibility of placebo effect from heparin treatment.

 

The same meta-analysis59 examined the role of aspirin alone compared with placebo or supportive care and found no significant benefit (three trials).

 

A recent randomised controlled trial reported a high success rate with aspirin alone and no significant benefit in live birth rate with the addition of heparin. However, this study included women with low titres of aPL, some of whom were randomised at up to 12 weeks of gestation, by which time most of aPL-related pregnancy losses would have already occurred.

 

Pregnancies associated with aPL treated with aspirin and heparin remain at high risk of complications during all three trimesters.” [2]

 

A 2004 Canadian guideline on antiphospholipid syndrome says:

 

“For women with APS-associated complications of pregnancy, prophylaxis with LMWH or heparin, with or without ASA, can be recommended on the basis of randomized controlled trials showing improved pregnancy outcomes.
Prophylactic LMWH or heparin for pregnant women with APS and previous thrombosis is recommended by extrapolation from the experience with other thrombophilic disorders, but this has not been specifically addressed in trials.” [3]

 

An e-Medicine article on antiphospholipid syndrome offers the following advice:

 

“In women with well-recognized obstetric APS, anticoagulant prophylaxis is recommended during pregnancy and the postpartum period. Pregnant women with APS are considered at risk of thrombosis and pregnancy loss. Data suggest low-dose aspirin and heparin (either unfractionated heparin or LMWH) are the treatments of choice for prevention of pregnancy loss in pregnant women with APS and previous pregnancy losses. Pregnant women with APS and a history of thrombosis but no pregnancy loss only require treatment with heparin. Treatment is optional for patients with no history of pregnancy loss or thrombosis.” [4]

 

Given that these secondary publications are over two years old, we searched the Medline databases for additional studies comparing low dose aspirin and heparin to aspirin alone in the prevention of miscarriage in women with antiphospholipid syndrome but found no additional studies.

 

References
1. Empson M, Lassere M, Craig J, Scott J. Prevention of recurrent miscarriage for women with antiphospholipid antibody or lupus anticoagulant. Cochrane Database of Systematic Reviews 2005, Issue 2. Art. No.: CD002859. DOI: 10.1002/14651858.CD002859.pub2. (http://www.mrw.interscience.wiley.com/cochrane/clsysrev/articles/CD002859/frame.html)
2. Royal College of Obstetricians and Gynaecologists. The investigation and treatment of couples with recurrent miscarriage.  Revised May 2003. (http://www.rcog.org.uk/resources/Public/pdf/Recurrent_Miscarriage_No17.pdf)
3. Thrombosis Interest Group of Canada. The antophospholipid syndrome. June 2004. (http://www.tigc.org/eguidelines/antiphoslipid04.htm).
4. Carsons S. Antiphospholipid syndrome. e-Medicine. December 2004. (http://www.emedicine.com/med/topic2923.htm).

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