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Increased activation of blood coagulation in pregnant women with the Factor V Leiden mutation
Authors:Ulla Kjellberg  Marianne van Rooijen  Katarina Bremme  Margareta Hellgren
Affiliation:1. Department of Obstetrics, Sahlgrenska University Hospital, Gothenburg, Sweden;2. Section for the Health of Women and Children, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Sweden;3. Department of Obstetrics and Gynaecology, Karolinska University Hospital, Stockholm, Sweden;4. Department of Women’s and Children’s Health, Karolinska Institutet, Stockholm, Sweden;5. Department of Antenatal Care, Närhälsan Primary Care, Västra Götaland, Sweden
Abstract:

Background

The risk of venous thromboembolism is enhanced in pregnant carriers of the Factor V Leiden mutation. The primary aim of the study was to compare prothrombin fragments 1 + 2, soluble fibrin and D-dimer levels in pregnant Factor V Leiden mutation carriers with those in non-carriers. Secondary aims were to evaluate whether these biomarkers could predict placenta-mediated complications or venous thromboembolism, and to study blood coagulation after caesarean section with thromboprophylaxis and after vaginal delivery without thromboprophylaxis.

Material/Methods

Prothrombin fragments 1 + 2, soluble fibrin and D-dimer levels were studied longitudinally in 476 carriers with singleton pregnancies from gestational weeks 23–25 until 8–10 weeks postpartum.

Results

Prothrombin fragments 1 + 2 and D-dimer levels gradually increased during pregnancy. D-dimer levels were higher in carriers, both during pregnancy and puerperium, compared to non-carriers. D-dimer levels above 0.5 mg/l were found in about 30% and 20% of the heterozygous carriers at 4–5 and 8–10 weeks postpartum, respectively. Soluble fibrin levels were mainly unchanged during pregnancy, with no difference between carriers and non-carriers. Biomarker levels were similar in carriers with uncomplicated and complicated pregnancies.

Conclusion

Higher D-dimer levels indicate increased blood coagulation and fibrinolysis activity in carriers. The high proportion of carriers with D-dimer levels exceeding 0.5 mg/l postpartum must be considered when assessing the probability of venous thromboembolism. Large overlaps in biomarker levels in normal and complicated pregnancies suggest that these biomarkers cannot be used as predictors. Thromboprophylaxis following caesarean section may prevent increased activation of blood coagulation.
Keywords:APC  activated protein C  c  s  caesarean section  CV  coefficient of variation  DIC  disseminated intravascular coagulation  DVT  deep vein thrombosis  ELISA  enzyme-linked immunosorbent assay  FVL  Factor V Leiden  F1     2  prothrombin fragments 1     2  IUFD  intrauterine fetal death  LMHW  low molecular weight heparin  r  Pearson&rsquo  s correlation coefficient  SD  standard deviation  SGA  small for gestational age  SF  soluble fibrin  VTE  venous thromboembolism
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