Subscribe to RSS
Placental Pathological Findings following Adjusting Enoxaparin Dosage in Thrombophilic Women: Secondary Analysis of a Randomized Controlled Trial
04 September 2018
25 October 2018
31 December 2018 (online)
Objective Randomized trials showed no improvement in pregnancy outcomes with the use of low molecular weight heparin (LMWH) to prevent placenta-mediated pregnancy complications (PMPCs) among thrombophilic women. However, the effect of treatment on placental findings was not examined. We aimed to examine the occurrence of placental vascular lesions in thrombophilic women treated with LMWH dose adjusted according to anti-factor Xa compared with a fixed dose.
Study Design This study was a secondary analysis of a randomized trial designed to examine whether LMWH dose adjusted according to anti-factor Xa levels compared with a fixed dose would reduce the risk of PMPC. Eligible women were randomly allocated in a 1:1 ratio to either a fixed dose of 40 mg daily LMWH (fixed dose group) or adjusted dose according to anti-factor Xa levels (adjusted dose group). Placentas were examined by the same perinatal pathologist who was blinded to group allocation. The primary outcome for this analysis was the incidence of maternal placental vascular lesions.
Results During the study period, 88 placentas were examined; 41 and 47 from the fixed and adjusted dose groups, respectively. Demographics, obstetrics and types of thrombophilias were similar between the groups. Maternal placental vascular lesions were observed in 23 (56.1%) and 21 (44.68%) placentas (p = 0.28) and foetal placental vascular lesions in 2 (4.88%) and 1 (2.13%) placentas (p = 0.59) in the fixed and adjusted groups, respectively.
Conclusion Adjusted dose of enoxaparin according to anti-factor Xa levels compared with a fixed dose did not affect placental vascular lesions in thrombophilic women.
Keywordslow molecular weight heparin - thrombophilia - pregnancy - placental vascular lesions - adjusted dosage
The manuscript has been read and approved for submission by all qualified authors.
- 1 Berg CJ, Atrash HK, Koonin LM, Tucker M. Pregnancy-related mortality in the United States, 1987-1990. Obstet Gynecol 1996; 88 (02) 161-167
- 2 Stillbirth Collaborative Research Network Writing Group. Causes of death among stillbirths. JAMA 2011; 306 (22) 2459-2468
- 3 van Rijn BB, Hoeks LB, Bots ML, Franx A, Bruinse HW. Outcomes of subsequent pregnancy after first pregnancy with early-onset preeclampsia. Am J Obstet Gynecol 2006; 195 (03) 723-728
- 4 Salim R, Czarnowicki T, Nachum Z, Shalev E. The impact of close surveillance on pregnancy outcome among women with a prior history of antepartum complications attributed to thrombosis: a cohort study. Reprod Biol Endocrinol 2008; 6: 55
- 5 van Walraven C, Mamdani M, Cohn A, Katib Y, Walker M, Rodger MA. Risk of subsequent thromboembolism for patients with pre-eclampsia. BMJ 2003; 326 (7393): 791-792
- 6 Jacobsen AF, Skjeldestad FE, Sandset PM. Ante- and postnatal risk factors of venous thrombosis: a hospital-based case-control study. J Thromb Haemost 2008; 6 (06) 905-912
- 7 Rodger MA, Hague WM, Kingdom J. , et al; TIPPS Investigators. Antepartum dalteparin versus no antepartum dalteparin for the prevention of pregnancy complications in pregnant women with thrombophilia (TIPPS): a multinational open-label randomised trial. Lancet 2014; 384 (9955): 1673-1683
- 8 Skeith L, Carrier M, Kaaja R. , et al. A meta-analysis of low-molecular-weight heparin to prevent pregnancy loss in women with inherited thrombophilia. Blood 2016; 127 (13) 1650-1655
- 9 Salim R, Nachum Z, Gavish I, Romano S, Braverman M, Garmi G. Adjusting enoxaparin dosage according to anti-FXa levels and pregnancy outcome in thrombophilic women. A randomised controlled trial. Thromb Haemost 2016; 116 (04) 687-695
- 10 Mousa HA, Alfirevic I Z. Do placental lesions reflect thrombophilia state in women with adverse pregnancy outcome?. Hum Reprod 2000; 15 (08) 1830-1833
- 11 Kingdom JC, Drewlo S. Is heparin a placental anticoagulant in high-risk pregnancies?. Blood 2011; 118 (18) 4780-4788
- 12 Redline RW. Thrombophilia and placental pathology. Clin Obstet Gynecol 2006; 49 (04) 885-894
- 13 Dizon-Townson DS, Meline L, Nelson LM, Varner M, Ward K. Fetal carriers of the factor V Leiden mutation are prone to miscarriage and placental infarction. Am J Obstet Gynecol 1997; 177 (02) 402-405
- 14 Sebire NJ, Backos M, El Gaddal S, Goldin RD, Regan L. Placental pathology, antiphospholipid antibodies, and pregnancy outcome in recurrent miscarriage patients. Obstet Gynecol 2003; 101 (02) 258-263
- 15 Heller DS, Rush D, Baergen RN. Subchorionic hematoma associated with thrombophilia: report of three cases. Pediatr Dev Pathol 2003; 6 (03) 261-264
- 16 Duhl AJ, Paidas MJ, Ural SH. , et al; Pregnancy and Thrombosis Working Group. Antithrombotic therapy and pregnancy: consensus report and recommendations for prevention and treatment of venous thromboembolism and adverse pregnancy outcomes. Am J Obstet Gynecol 2007; 197 (05) 457.e1-457.e21
- 17 Bar J, Kovo M, Schraiber L, Shargorodsky M. Placental maternal and fetal vascular circulation in healthy non-obese and metabolically healthy obese pregnant women. Atherosclerosis 2017; 260: 63-66
- 18 Kovo M, Zion-Saukhanov E, Schreiber L. , et al. The effect of maternal obesity on pregnancy outcome in correlation with placental pathology. Reprod Sci 2015; 22 (12) 1643-1648
- 19 Rodger MA, Gris JC, de Vries JIP. , et al; Low-Molecular-Weight Heparin for Placenta-Mediated Pregnancy Complications Study Group. Low-molecular-weight heparin and recurrent placenta-mediated pregnancy complications: a meta-analysis of individual patient data from randomised controlled trials. Lancet 2016; 388 (10060): 2629-2641
- 20 Arias F, Romero R, Joist H, Kraus FT. Thrombophilia: a mechanism of disease in women with adverse pregnancy outcome and thrombotic lesions in the placenta. J Matern Fetal Med 1998; 7 (06) 277-286
- 21 Gogia N, Machin GA. Maternal thrombophilias are associated with specific placental lesions. Pediatr Dev Pathol 2008; 11 (06) 424-429
- 22 Rogers BB, Momirova V, Dizon-Townson D. , et al. Avascular villi, increased syncytial knots, and hypervascular villi are associated with pregnancies complicated by factor V Leiden mutation. Pediatr Dev Pathol 2010; 13 (05) 341-347
- 23 Ariel I, Anteby E, Hamani Y, Redline RW. Placental pathology in fetal thrombophilia. Hum Pathol 2004; 35 (06) 729-733
- 24 Rodger MA, Paidas M, McLintock C. , et al. Inherited thrombophilia and pregnancy complications revisited. Obstet Gynecol 2008; 112 (2 Pt 1): 320-324
- 25 Alfirevic Z, Roberts D, Martlew V. How strong is the association between maternal thrombophilia and adverse pregnancy outcome? A systematic review. Eur J Obstet Gynecol Reprod Biol 2002; 101 (01) 6-14
- 26 Vern TZ, Alles AJ, Kowal-Vern A, Longtine J, Roberts DJ. Frequency of factor V(Leiden) and prothrombin G20210A in placentas and their relationship with placental lesions. Hum Pathol 2000; 31 (09) 1036-1043
- 27 D'Souza R, Keating S, Walker M, Drewlo S, Kingdom J. Unfractionated heparin and placental pathology in high-risk pregnancies: secondary analysis of a pilot randomized controlled trial. Placenta 2014; 35 (10) 816-823