Long-term consequences of pregnancy-related venous thrombosis
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AbstractBackground: Venous thrombosis (VT) is among the leading causes of maternal mortality in countries with high standards of perinatal care; however the long-term outcomes of pregnancy-related VT are unknown.
Aims: To assess the long-term prevalence of post-thrombotic syndrome (PTS), a frequently occurring chronic complication after deep vein thrombosis (DVT), to identify possible predictors for PTS, and to evaluate disease specific quality of life (QOL) after pregnancy-related DVT as compared with a control group. We also aimed to assess the mortality and incidence of cancer after VT in this population.
Materials and Methods: The Norwegian Patient Register and the Medical Birth Registry of Norway were used to identify cases of women with a first-ever pregnancy-related VT during 1990-2003 from 18 Norwegian hospitals. Women without VT matched for time of delivery were selected by the Medical Birth Registry as controls. All VTs were validated using the hospital medical records. Total 559 cases and 1229 controls were identified and were invited to answer a comprehensive questionnaire. 313 cases and 353 controls met to participate in 2006. The questionnaire included self-reported Villalta score for the assessment of PTS and the disease specific QOL questionnaire VEINES-QOL/Sym. In 2012, the original study population of 1788 women was linked to the Norwegian Cause of Death Registry and the Cancer Registry of Norway.
Results: PTS was found in 42% of 204 women 3-16 years after a lower limb pregnancy-related DVT. Proximal DVT when occurring postnatal was the most important predictor for PTS. Higher age and smoking were also independently associated with PTS. Women with DVT reported reduced disease specific QOL compared with controls. Ten cases (1.8%) and 7 controls (0.6%) died during 13 years of follow-up. Mortality was significantly higher among cases compared with controls (hazard ratio 3.2, 95% confidence interval 1.2-8.5, P=0.018 when adjusted for age). The mortality among cases was also 19 times higher than among the age-adjusted Norwegian female population the first year after VT (standardized mortality ratio (SMR) 18.8, 95% CI 7.8-45.3), but thereafter the mortality was similar (SMR 0.9, 95% CI 0.4-2.0). Fifteen cases (2.7%) and 13 controls (1.1%) were diagnosed with cancer after index pregnancy and subsequent cancer was significantly more frequent among cases compared with controls (hazard ratio 2.6, 95% CI 1.3-5.6, p=0.011). Cases did not have higher incidence of cancer when comparing with the age-and sex-adjusted general population (standardized incidence ratio 1.0, 95% CI 0.6-1.7).
Conclusions: PTS was a common long-term complication after pregnancy-related DVT affecting almost half of the women and disease specific QOL in this population was reduced compared with a control group. Cases had significantly higher mortality and incidence of cancer than controls during 13 years of follow-up. When comparing with the age-adjusted Norwegian female population, mortality was increased only the first year after VT and incidence of cancer was similar.
List of papers. The papers are removed from the thesis due to publisher restrictions.
Paper I: Wik HS, Jacobsen AF, Sandvik L, Sandset PM. Prevalence and predictors for post-thrombotic syndrome three to 16 years after pregnancy-related venous thrombosis: a population-based, cross-sectional, case-control study. Journal of Thrombosis and Haemostasis 2012 May; 10:840-7. doi:10.1111/j.1538-7836.2012.04690.x
Paper II: Wik HS, Enden TR, Jacobsen AF, Sandset PM. Long-term quality of life after pregnancy-related deep vein thrombosis and the influence of socioeconomic factors and comorbidity. Journal of Thrombosis and Haemostasis 2011; 9: 1931–6. doi:10.1111/j.1538-7836.2011.04468.x
Paper III Wik HS, Jacobsen AF, Fagerland MW, Sandvik L, Sandset PM. Long-term mortality and incidence of cancer after pregnancy-related venous thrombosis: results of a population-based cohort study. Thrombosis Research 2013 Jun;131(6):497-501 doi:10.1016/j.thromres.2013.04.035