Question:
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A 40 year old woman with a 1.5 year history of DVT maintained on Warfarin is now 6 weeks pregnant. How should she be managed?
Answer:
Warfarin is a known teratogen. Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk1 (Evidence level IV) summarises the risks as follows:
“For all cases, only about 70% of pregnancies are expected to result in a normal infant. Exposure in the 6th–9th weeks of gestation may produce a pattern of defects termed the “fetal warfarin syndrome” with an incidence up to ≥25% in some series. Infants exposed before and after this period have had other congenital anomalies, but the relationship between warfarin and these defects is unknown. Infrequent central nervous system defects, which have greater clinical significance to the infant than the defects of the fetal warfarin syndrome, may be deformations related to hemorrhage and scarring with subsequent impaired growth of brain tissue. Spontaneous abortions, stillbirths, and neonatal deaths may also occur.”
Full details are available in the chapter on Coumarin Derivatives.
Drugs for Pregnant and Lactating Women2 (Evidence level IV) indicates that “a daily dose of >5mg is associated with a greater risk of an adverse outcome.” It goes on to suggest replacement with heparin between 6 and 12 weeks and substitution with heparin at 36 weeks to decrease the risk of haemorrhage at the time of birth.
The RCOG’s Green-top guideline, Reducing the risk of thrombosis and embolism during pregnancy and the puerperium3 (Evidence level Ib) provides full guidance on the assessment and management of women at risk. Relevant recommendations include:
- Management in collaboration with a haematologist
- Conversion to low molecular weight heparin
References:
1. Briggs GC, Freeman RK, Yaffe SJ. Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk. Philadelphia: LWW, 2011. (Fellows, Members and Trainees can access this reference text free of charge through the e-books section of the RCOG website: http://www.rcog.org.uk/our-profession/research-services/e-books)
2. Weiner CP, Buhimschi C. Drugs for Pregnant and Lactating Women. Philadelphia: Churchill Livingstone, 2004.
3. RCOG Green-top guideline n. 37. Reducing the risk of thrombosis and embolism during pregnancy and the puerperium. London: RCOG, 2009. http://www.rcog.org.uk/files/rcog-corp/GT37ReducingRiskThrombo.pdf
Search date: 27 September 2011
Evidence levels
Classification of evidence levels
Ia Evidence obtained from meta-analysis of randomised controlled trials.
Ib Evidence obtained from at least one randomised controlled trial.
IIa Evidence obtained from at least one well-designed controlled study without randomisation.
IIb Evidence obtained from at least one other type of well-designed quasi-experimental study.
III Evidence obtained from well-designed non-experimental descriptive studies, such as comparative studies, correlation studies and case studies.
IV Evidence obtained from expert committee reports or opinions and/or clinical experience of respected authorities.
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