Advances in Anticoagulation Therapy for Preeclampsia: A Systematic Review
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Keywords

Preeclampsia
Therapy
Anticoagulation
Thrombosis
Coagulation monitoring
Heparin

DOI

10.26689/aogr.v3i3.10854

Submitted : 2025-06-08
Accepted : 2025-06-23
Published : 2025-07-08

Abstract

Preeclampsia (PE) is a multisystem pregnancy disorder. Several pathological processes, such as vascular endothelial dysfunction, an imbalance between coagulation and anticoagulation, and changes in trophoblast characteristics, are involved in the development of PE. The article discusses the pathogenesis of PE. In the third trimester, a protective hypercoagulable state typically develops in normal pregnancies. However, in PE, this state is exacerbated, resulting in a thrombotic phenotype characterized by a systemic inflammatory response and activation of the clotting cascade. This article examines the potential mechanisms involved. The present treatment emphasizes the timely delivery of the fetus. The investigation of anticoagulant therapies is still ongoing, mainly focusing on aspirin and the use of low-molecular-weight heparin for drug-induced thrombosis prevention. In this review, we will summarize the recent findings of reported and ongoing anticoagulation therapy in the treatment of PE. This anticoagulant treatment strategy is essential for the improvement and prevention of PE.

References

Li P, Wang H, Guo L, et al., 2022, Association Between Gut Microbiota and Preeclampsia–Eclampsia: A Two-Sample Mendelian Randomization. BMC Medicine, 20: 443.

MacDonald T, Walker S, Hannan N, et al., 2022, Clinical Tools and Biomarkers to Predict Preeclampsia. EBioMedicine, 75.

Ma’ayeh M, Costantine M, 2020, Prevention of Preeclampsia. Seminars in Fetal and Neonatal Medicine, 25(5): 101123.

Ives C, Sinkey R, Rajapreyar I, et al., 2020, Preeclampsia—Pathophysiology and Clinical Presentations: JACC State-of-the-Art Review. Journal of the American College of Cardiology, 76(14): 1690–1702.

Jung E, Romero R, Yeo L, et al., 2022, The Etiology of Preeclampsia. American Journal of Obstetrics and Gynecology, 226(2): S844–S866.

Turbeville H, Sasser J, 2020, Preeclampsia Beyond Pregnancy: Long-Term Consequences for Mother and Child. American Journal of Physiology–Renal Physiology, 318(6): F1315–F1326.

Roberts J, Rich-Edwards J, McElrath T, et al., 2021, Subtypes of Preeclampsia: Recognition and Determining Clinical Usefulness. Hypertension, 77(5): 1430–1441.

Han C, Chen Y, Dong J, 2021, Prothrombotic State Associated with Preeclampsia. Current Opinion in Hematology, 28(5): 323–330.

Uzan J, Carbonnel M, Piconne O, et al., 2011, Pre-Eclampsia: Pathophysiology, Diagnosis, and Management. Vascular Health and Risk Management, 2011: 467–474.

Hauspurg A, Jeyabalan A, 2022, Postpartum Preeclampsia or Eclampsia: Defining Its Place and Management Among the Hypertensive Disorders of Pregnancy. American Journal of Obstetrics and Gynecology, 226(2): S1211–S1221.

Rolnik D, Nicolaides K, Poon L, 2022, Prevention of Preeclampsia with Aspirin. American Journal of Obstetrics and Gynecology, 226(2): S1108–S1119.

Katsi V, Kanellopoulou T, Makris T, et al., 2016, Aspirin vs Heparin for the Prevention of Preeclampsia. Current Hypertension Reports, 18: 1–8.

Zheng L, Xia B, Yuan Y, et al., 2022, Low-Molecular-Weight Heparin in Addition to Low-Dose Aspirin for Preventing Preeclampsia and Its Complications: A Systematic Review and Meta-Analysis. Frontiers in Cardiovascular Medicine, 9: 1073148.

McRae H, Militello L, Refaai M, 2021, Updates in Anticoagulation Therapy Monitoring. Biomedicines, 9(3): 262.

Lichota A, Szewczyk E, Gwozdzinski K, 2020, Factors Affecting the Formation and Treatment of Thrombosis by Natural and Synthetic Compounds. International Journal of Molecular Sciences, 21(21): 7975.

Weitz J, Fredenburgh J, 2017, Factors XI and XII as Targets for New Anticoagulants. Frontiers in Medicine, 4: 19.

Ramsis T, Ebrahim M, Fayed E, 2023, Synthetic Coumarin Derivatives with Anticoagulation and Antiplatelet Aggregation Inhibitory Effects. Medicinal Chemistry Research, 32(11): 2269–2278.

Neubauer K, Zieger B, 2022, Endothelial Cells and Coagulation. Cell and Tissue Research, 387(3): 391–398.

Terranova V, DiFlorio R, Lyall R, et al., 1985, Human Endothelial Cells Are Chemotactic to Endothelial Cell Growth Factor and Heparin. The Journal of Cell Biology, 101(6): 2330–2334.

Gierula M, Ahnström J, 2020, Anticoagulant Protein S—New Insights on Interactions and Functions. Journal of Thrombosis and Haemostasis, 18(11): 2801–2811.

Slovinski A, Hajjar L, Ince C, 2019, Microcirculation in Cardiovascular Diseases. Journal of Cardiothoracic and Vascular Anesthesia, 33(12): 3458–3468.

Guven G, Hilty M, Ince C, 2020, Microcirculation: Physiology, Pathophysiology, and Clinical Application. Blood Purification, 49(1–2): 143–150.

Lupu F, Kinasewitz G, Dormer K, 2020, The Role of Endothelial Shear Stress on Haemodynamics, Inflammation, Coagulation and Glycocalyx During Sepsis. Journal of Cellular and Molecular Medicine, 24(21): 12258–12271.

Sagris M, Theofilis P, Antonopoulos A, et al., 2021, Inflammation in Coronary Microvascular Dysfunction. International Journal of Molecular Sciences, 22(24): 13471.

Russo V, Falco L, Tessitore V, et al., 2023, Anti-Inflammatory and Anticancer Effects of Anticoagulant Therapy in Patients with Malignancy. Life, 13(9): 1888.

Makedonov I, Kahn S, Abdulrehman J, et al., 2022, Prevention of the Postthrombotic Syndrome with Anticoagulation: A Narrative Review. Thrombosis and Haemostasis, 122(8): 1255–1264.

Raguema N, Moustadraf S, Bertagnolli M, 2020, Immune and Apoptosis Mechanisms Regulating Placental Development and Vascularization in Preeclampsia. Frontiers in Physiology, 11: 499034.

Mierzynski R, Poniedzialek-Czajkowska E, Kimber-Trojnar Z, et al., 2014, Anticoagulant Therapy in Pregnant Patients with Metabolic Syndrome: A Review. Current Pharmaceutical Biotechnology, 15(1): 47–63.

Stanhewicz A, Nuckols V, Pierce G, 2021, Maternal Microvascular Dysfunction During Preeclamptic Pregnancy. Clinical Science, 135(9): 1083–1101.

He X, Ji Y, Yu M, et al., 2021, Chorioretinal Alterations Induced by Preeclampsia. Journal of Ophthalmology, 2021: 8847001.

Weyer G, Nolan C, Macdonald R, 2006, Evidence-Based Cerebral Vasospasm Management. Neurosurgical Focus, 21(3): 1–10.

Barr L, Liblik K, Johri A, et al., 2022, Maternal Cardiovascular Function Following a Pregnancy Complicated by Preeclampsia. American Journal of Perinatology, 39(10): 1055–106.

McLaughlin K, Drewlo S, Parker J, et al., 2015, Current Theories on the Prevention of Severe Preeclampsia with Low-Molecular Weight Heparin. Hypertension, 66(6): 1098–1103.

Lefkou E, Varoudi K, Pombo J, et al., 2020, Triple Therapy with Pravastatin, Low Molecular Weight Heparin and Low Dose Aspirin Improves Placental Haemodynamics and Pregnancy Outcomes in Obstetric Antiphospholipid Syndrome in Mice and Women Through a Nitric Oxide-Dependent Mechanism. Biochemical Pharmacology, 182: 114217.

Morelli S, Mandal M, Goldsmith L, et al., 2015, The Maternal Immune System During Pregnancy and Its Influence on Fetal Development. Research and Reports in Biology, 2015: 171–189.

Luley L, Schumacher A, Mulla M, et al., 2015, Low Molecular Weight Heparin Modulates Maternal Immune Response in Pregnant Women and Mice with Thrombophilia. American Journal of Reproductive Immunology, 73(5): 417–427.

D’Ippolito S, Di Nicuolo F, Marana R, et al., 2012, Emerging Nonanticoagulant Role of Low Molecular Weight Heparins on Extravillous Trophoblast Functions and on Heparin Binding–Epidermal Growth Factor and Cystein-Rich Angiogenic Inducer 61 Expression. Fertility and Sterility, 98(4): 1028–1036.