Enoxaparin for the secondary prevention of placental vascular complications in women with abruptio placentae

Summary

Administration of heparin in the secondary prevention of placental vascular complications is still experimental. In women with a previous placental abruption, we investigated the effectiveness of enoxaparin, a low-molecular-weight heparin, in preventing these complications. Between January 2000 and January 2009, 160 women from the NOHA First cohort, with previous abruptio placentae but no foetal loss during their first pregnancy and negative for antiphospholipid antibodies, were randomised to either a prophylactic daily dose of enoxaparin starting from the positive pregnancy test (n=80), or no enoxaparin (n=80). The primary outcome was a composite of at least one of the following: abruptio placentae, preeclampsia, birthweight < 5^th percentile, or foetal loss after 20 weeks. Enoxaparin was associated with a lower frequency of primary outcome: 12.5% (n=10/80) vs. 31.3 % (25/80), p=0.004, adjusted hazard ratio = 0.37, 95% confidence interval (0.18–0.77), p=0.011. Enoxaparin was safe, with no obvious side-effect, no thrombocytopenia nor major bleeding event excess. This pilot study shows that enoxaparin given early during the second pregnancy decreases the occurrence of placental vascular complications in women with a previous placental abruption during their first pregnancy.

Keywords

Pregnancy - placental abruption - placental vascular complications - low-molecular-weight heparin - randomised controlled trial

• References

• 1 Naeye RL. Pregnancy hypertension, placental evidences of low uteroplacental blood flow, and spontaneous premature delivery. Hum Pathol 21989 20: 441-444.
• 2 Rasmussen S, Irgens LM, Dalaker K. A history of placental dysfunction and risk of placental abruption. Paediatr Perinat Epidemiol 1999; 13: 9-21.
• 3 Ananth CV, Getahun D, Peltier MR. et al. Placental abruption in term and preterm gestations: evidence for heterogeneity in clinical pathways. Obstet Gynecol 2006; 107: 785-792.
• 4 Ananth CV, Wilcox AJ. Placental abruption and perinatal mortality in the United States. Am J Epidemiol 2001; 153: 332-337.
• 5 Ananth CV, Peltier MR, Chavez MR. et al. Recurrence of ischemic placental disease. Obstet Gynecol 2007; 110: 128-133.
• 6 Rasmussen S, Irgens LM. Occurrence of placental abruption in relatives. Br J Obstet Gynaecol 2009; 11: 693-699.
• 7 Duley L, Henderson-Smart DJ, Meher S. et al. Antiplatelet agents for preventing preeclampsia and its complications. Cochrane Databases Syst Rev 2007; 2: CD004659.
• 8 Robertson L, Wu O, Laghorne P. et al. Risk and Economic Assessment of Thrombophilia Screening (TREATS) Study. Br J Haematol 2005; 132: 171-196.
• 9 Brenner B. Clinical management of thrombophilia-related placental vascular complications. Blood 2004; 103: 1003-1009.
• 10 Bates SM, Greer IA, Pabinger I. et al. Venous thromboembolism, thrombophilia, antithrombotic therapy, and pregnancy: Amercian College of Chest Physicians Evidence-Based Clinical Practice Guideliness (8^th edition). Chest 2008; 133 (Suppl. 06) 844S-886S.
• 11 Rey E, Garneau P, David M. et al. Dalteparin for the prevention of recurrence of placental-mediated complications of pregnancy in women without thrombophilia: a pilot randomized controlled trial. J Thromb Haemost 2009; 7: 58-64.
• 12 Lissalde-Lavigne G, Fabbro-Peray P, Cochery-Nouvellon E. et al. Factor V Leiden and prothrombin G20210A polymorphisms as risk factors for miscarriage during a first intended pregnancy: the matched case-control ‘NOHA first’ study. J Thromb Haemost 2005; 3: 2178-2184.
• 13 Cochery-Nouvellon E, Mercier E, Lissalde-Lavigne G. et al. Homozygosity for the C46T polymorphism of the F12 gene is a risk factor for venous thrombosis during the first pregnancy. J Thromb Haemost 2007; 5: 700-707.
• 14 Schulman S, Kearon C. on behalf of the subcommittee on control of anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. Scientific and Standardization Committee Communication. J Thromb Haemost 2005; 3: 692-694.
• 15 Wisser J, Dirschedl P, Krone S. Estimation of gestational age by transvaginal sonographic measurement of greatest embryonic length in dated human embryos. Ultrasound Obstet Gynecol 1994; 4: 457-462.
• 16 Salomon LJ, Duyme M, Crequat J. et al. French fetal biometry: reference equations and comparison with other charts. Ultrasound Obstet Gynecol 2006; 28: 193-198.
• 17 Mello G, Parretti E, Fatini C. et al. Low-molecular weight heparin lowers the recurence rate of preclampsia and restores the physiological vascular changes in angiotensin-converting enzyme DD women. Hypertension 2005; 45: 86-91.
• 18 Smith GC, Crossley JA, Aitken DA. et al. Circulating angiogenic factors in early pregnancy and risk of preeclampsia, intrauterine growth restriction, spontaneous preterm birth, and stillbirth. Obstet Gynecol 2007; 109: 1316-1324.
• 19 Ananth CV, Cnattingius S. Influence of maternal smoking on placental abruption in successive pregnancies: a population-based prospective cohort study in Sweden. Am J Epidemiol 2007; 166: 289-295.
• 20 Hossain N, Schatz F, Paidas MJ. Heparin and maternal fetal interface: why should it work to prevent pregnancy complications?. Thromb Res 2009; 124: 653-655.