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Three Part Question

In [pregnant women with suspected PE] presenting to the ED is [heparin better than warfarin] for better [outcome]?

Clinical Scenario

A 25-year old pregnant woman presents to the ED with a suspected PE. You start her on LMWH but wonder if warfarin is safe to use as well.

Search Strategy

All EBM Reviews - Cochrane DSR, ACP Journal Club, DARE, CCTR, CMR, HTA, and NHSEED 2nd Quarter 2008. EMBASE 1996 to 2008 week 25. Medline 1950-Week 2 June 2008 using the OVID interface. CINAHL 1982 to June Week 2 2008
([{pregnanc$.mp. OR exp Pregnancy OR exp Pregnancy Complications or pregnant.mp. OR exp Pregnant Women}] AND [exp Pulmonary Embolism OR pulmonary embolu$.mp. OR pulmonary embolus.mp. OR exp Venous Thrombosis/ pleuri$.mp. OR pulmonary embol$.mp.]) AND {exp Heparin, Low-Molecular-Weight OR exp Heparin OR heparin$.mp. OR warfarin$.mp. OR exp Warfarin OR Coumarin$.mp. or exp Coumarins OR unfractionated heparin$.mp.} AND {safety$.mp. or exp Safety OR outcome$.mp. OR exp Pregnancy Outcome OR exp Treatment Outcome}
LIMIT to human AND english.

Search Outcome

44 papers were found of which 43 were irrelevant or of insufficient quality. Hand searching the reference sections identified one further paper.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Barbour et al 1995 Canada	Critical review of twenty-nine articles, selected from the one hundred and fifty six identified.	Systematic Review	Warfarin treatment in 1st trimester of pregnancy	Embryopathy incidence of 0-30% (stippled epiphyses, and limb and nasal hypoplasia).	No level one studies included, and only two were level two trials.Search strategy not apparent.
			Warfarin treatment in 2nd and 3rd trimester	Should be avoided due to CNS abnormalities.
			Review of 1325 pregnancies from 186 studies	16.9% incidence of adverse outcomes with the use of warfarin.
			Rates of spontaneous abortion and miscarriage.	Elevated (No values stated)
			18 Chinese pregnant women treated with warfarin in the 1st trimester	2/3 had nasal hypoplasia and hypertelorism. None had limb hypoplasia.
Greer IA 2005 Scotland	Systematic Review from 1996 to October 2005.Six papers which looked at warfarin use for venous thrombo-embolic disease in pregnancy.	Systematic Review	Coumarin use.	Cause teratogenesis and are associated with foetal bleeding.	No percentages or CI intervals given for any of the outcomes.
			Coumarin embryopathy.	Exposure between 6-9 wks gesatation (Incidence 5%)
			Midfacial hypoplasia andother skeletal abnormalities	Associated with ectopic calcification.
			Prenatal exposure to coumarins	Ass. With increased risk low IQ and minor neurological dysfunction.
			Coumarin use at the time of delivery.	Risk of maternal and foetal haemorrhage

Comment(s)

Coumarins are associated with embryopathy when used in pregnancy. Warfarin has the potential to cross the placenta and can cause foetal bleeding. Whereas heparin cannot cross the placenta so is safer to use. Warfarin is safe to use when breast-feeding; it does not pass into the milk. Only two papers looked at warfarin therapy for VTD, many others concentrated on warfarin use for other clinical conditions e.g. mitral valve disease.

Clinical Bottom Line

Warfarin should be avoided in pregnancy if possible.

References

1. Barbour LA, Pickard J. Controversies in thromboembolic disease during pregnancy: a critical review. Obs & gyne. 1995 Oct;86(4 Pt 1):621-33.
2. Greer IA Venous thromboembolism and anticoagulant therapy in pregnancy. Gend Med. 2005;2 Suppl A:S10-7.