Abstract

Abstract 1142

Background

Pregnancy is associated with a hypercoagulable state, with the highest risk of venous thromboembolism (VTE) occurring during the postpartum period. This risk is further increased by the presence of inherited thrombophilic states, including Factor V Leiden (FVL) or the prothrombin gene variant (PGV), such that many clinicians provide routine postpartum thromboprophylaxis for this group. Publications examining the absolute incidence of pregnancy associated VTE in carriers of FVL and PGV report a rate of only 0–1% over the combined antepartum and 6–12 week postpartum periods. However, given that at least 50% of pregnancy associated VTE occur postpartum, the daily risk of VTE may be sufficiently high to warrant thromboprophylaxis during this period.

Objectives
  1. To determine the absolute rate of postpartum VTE among a prospectively enrolled cohort of FVL or PGV positive women.

  2. To determine the pooled proportion of postpartum VTE in this population through a systematic review of published prospective cohort studies.

Methods

We performed a substudy analysis of the prospective Ottawa and Kingston (OaK) birth cohort study, in which women presenting for routine antenatal care were followed throughout pregnancy until delivery. Genotyping for FVL and PGV by polymerase chain reaction was performed for all participants after completion of the postpartum period. 336 women who enrolled through the participating Ottawa hospitals and identified as FVL or PGV positive were eligible for the current analysis. Data relating to the occurrence of VTE during the 6-week post partum period were obtained for 201/336 women through medical record review or direct contact by a study investigator. The main outcome measure was the proportion of objectively confirmed VTE within 6 weeks of delivery among participants with heterozygous FVL or PGV.

Eligible articles were identified through a comprehensive search of the MEDLINE database. Inclusion criteria included a) prospective cohort design of women completing pregnancy during the study period; b) assessment of all participants for FVL and/or PGV; c) observation of participants throughout the postpartum period; d) report of objectively confirmed VTE during the postpartum period. Studies limited to women with previous pregnancy complications or previous VTE were excluded. The pooled proportion of postpartum VTE was calculated from combination of reported postpartum VTE rates and the current study results.

Results

No postpartum VTE occurred among the 188 participants heterozygous for FVL or PGV alone. The proportion of VTE among the population with isolated heterozygous FVL and/or PGV was 0% (95% CI 0 to 2.0). One postpartum event was documented in a heterozygous PGV carrier with coexisting protein C deficiency. No events were documented among 12 women with homozygous or compound heterozygous defects. Superficial vein thrombosis was diagnosed in two carriers of FVL.

Ten publications examining the rate of postpartum VTE among FVL or PGV carriers were identified in the systematic review. (Table 1) The pooled proportion of postpartum VTE among those who did not receive postpartum prophylaxis was 0.6% (95% CI 0.2 to 1.3) for heterozygous carriers of FVL and 0% (95% CI 0 to 1.6) for PGV heterozygotes.

Conclusion

The absolute risk of VTE among asymptomatic carriers of FVL or PGV appears sufficiently low to withhold postpartum prophylaxis.

Table 1

Pooled Proportions of Postpartum VTE

StudyProportion Receiving ProphylaxisVTE Proportion: No prophylaxis (95% CI)VTE Proportion: Prophylaxis or unknown prophylaxis (95% CI)
FVL - Heterozygous    
Dizon-Townson 1997 NR – 0/13 
Lindqvist 1999 4/263 2/259 1/4 
Eichinger 1999 None 0/11 – 
Murphy 2000 NR – 0/16 
Middledorp 2001 9/17 0/8 0/9 
Salomen 2004 None 0/23 – 
Dizon-Townson 2005 None 0/134 – 
Clark 2008 NR – 0/142 
Kjellberg 2010 128/472 3/344 0/128 
Current Study 14/139 0/125 0/14 
Pooled Proportion  5/904 = 0.6% (0.2–1.3) 1/326 = 0.3% (0.1–1.7) 
PGV - Heterozygous    
Salomen 2004 None 0/27 – 
Silver 2010 None 0/156 – 
Current Study* 1/48 0/47 0/1 
Pooled Proportion  0/230 = 0% (0–1.6) Insufficient data for pooled proportion 
StudyProportion Receiving ProphylaxisVTE Proportion: No prophylaxis (95% CI)VTE Proportion: Prophylaxis or unknown prophylaxis (95% CI)
FVL - Heterozygous    
Dizon-Townson 1997 NR – 0/13 
Lindqvist 1999 4/263 2/259 1/4 
Eichinger 1999 None 0/11 – 
Murphy 2000 NR – 0/16 
Middledorp 2001 9/17 0/8 0/9 
Salomen 2004 None 0/23 – 
Dizon-Townson 2005 None 0/134 – 
Clark 2008 NR – 0/142 
Kjellberg 2010 128/472 3/344 0/128 
Current Study 14/139 0/125 0/14 
Pooled Proportion  5/904 = 0.6% (0.2–1.3) 1/326 = 0.3% (0.1–1.7) 
PGV - Heterozygous    
Salomen 2004 None 0/27 – 
Silver 2010 None 0/156 – 
Current Study* 1/48 0/47 0/1 
Pooled Proportion  0/230 = 0% (0–1.6) Insufficient data for pooled proportion 

FVL: factor V Leiden, PGV: prothrombin gene variant, NR: not reported.

*

Data regarding postpartum prophylaxis unavailable in one case.

Disclosures:

Ramsay:Heart and Stroke Foundation of Canada: Research Funding; Canadian Institutes of Health Research: Research Funding. Rodger:Canadian Institutes of Health Research: Research Funding; Heart and Stroke Foundation of Canada: Research Funding.

Author notes

*

Asterisk with author names denotes non-ASH members.