Pemberian Antikoagulan pada Kehamilan dengan Risiko Trombosis
DOI:
https://doi.org/10.56260/sciena.v5i5.383Keywords:
Kehamilan, tromboemboli vena, antikoagulan, LMWH, UFH, tromboprofilaksis, hiperkoagulabilitasAbstract
Tromboemboli vena (TEV) merupakan komplikasi serius yang dapat terjadi selama kehamilan dan masa nifas. Kehamilan secara fisiologis menciptakan keadaan hiperkoagulabel akibat perubahan hemostasis, termasuk peningkatan faktor koagulasi dan penurunan aktivitas fibrinolitik. Kondisi ini meningkatkan risiko TEV sekitar 4–5 kali lipat dibandingkan populasi non-hamil, dengan insidensi tertinggi terjadi pada 6 minggu pertama pascapersalinan. Secara global, kejadian TEV diperkirakan mencapai 1–2 kasus per 1.000 kehamilan. Risiko meningkat signifikan pada wanita dengan trombofilia, riwayat TEV sebelumnya, imobilisasi, obesitas, kehamilan ganda, atau pasca tindakan pembedahan. Antikoagulan merupakan terapi utama untuk pencegahan dan penatalaksanaan TEV dalam kehamilan. Heparin tidak terfraksinasi (UFH) dan low molecular weight heparin (LMWH) merupakan pilihan yang aman karena tidak melintasi plasenta, dengan LMWH lebih disukai karena profil farmakokinetiknya yang stabil dan risiko efek samping lebih rendah. Sebaliknya, warfarin bersifat teratogenik dan DOACs belum direkomendasikan karena keterbatasan data keamanan. Penulisan tinjauan pustaka ini bertujuan memberikan gambaran komprehensif mengenai epidemiologi, faktor risiko, serta prinsip pemilihan dan pemberian antikoagulan selama kehamilan, untuk mendukung pengambilan keputusan klinis yang tepat.
References
. Ortel TL, Neumann I, Ageno W. American society of hematology 2020 guidelines for management of venous thromboembolism: Treatment of deep vein thrombosis and pulmonary embolism. Blood Adv. 2020;4(19):4693-4738.
. Siegal DM, Eikelboom JW, Lee SF, Rangarajan S, Bosch J, Zhu J, et al. Variations in Incidence of Venous Thromboembolism in Low-, Middle- and High-Income Countries. Cardiovasc Res. 2021;117(2):1-25.
. Tagalakis V, Patenaude V, Kahn SR, Suissa S. Incidence of and mortality from venous thromboembolism in a real-world population: The Q-VTE study cohort. Am J Med. 2013;126(9):13-21.
. Kearon C, Akl EA, Comerota AJ. Antithrombotic therapy for VTE disease: Antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012(14):419-496.
. Varrias D, Spanos M, Kokkinidis DG, Zoumpourlis P, Kalaitzopoulos DR. Venous Thromboembolism in Pregnancy: Challenges and Solutions. Vasc Health Risk Manag. 2023;19:469-484.
. Heit J, Kobbervig C, James A, Petterson T, Bailey K, Melton Iii J. Trends in the Incidence of Venous Thromboembolism during. Ann Intern Med. 2005;143(10):697-706.
. Philipson J, Thunström E, Svanvik T, et a. Incidence and time trends of pregnancy-related first-times venous thromboembolism: a 33-year Swedish birth registry study. J Thromb Haemost. 2025:1-10.
. Kamel H, Navi BB, Sriram N, Hovsepian DA, Devereux RB, Elkind MSV. Risk of a Thrombotic Event after the 6-Week Postpartum Period. N Engl J Med. 2014:1-9.
. ACOG. American College of Obstetricians and Gynecologists - ACOG Practice Bulletin No. 196: Thromboembolism in Pregnancy. Am Coll Obstet Gynecol. 2018;132(1):1-17.
. Patel JP, Green B, Patel RK, Marsh MS, Davies JG, Arya R. Population pharmacokinetics of enoxaparin during the antenatal period. Circulation. 2013;128(13):1462-1469.
. Eke AC. An update on the physiologic changes during pregnancy and their impact on drug pharmacokinetics and pharmacogenomics. J Basic Clin Physiol Pharmacol. 2022;33(5):581-598.
. Lameijer H, Aalberts JJJ, van Veldhuisen DJ, Meijer K, Pieper PG. Efficacy and safety of direct oral anticoagulants during pregnancy; a systematic literature review. Thromb Res. 2018;169:123-127.
. Romualdi E, Dentali F, Rancan E. Anticoagulant therapy for venous thromboembolism during pregnancy: A systematic review and a meta-analysis of the literature. J Thromb Haemost. 2013;11(2):270-281.
. Lapelusa A, Dave HD. Physiology, Hemostasis. StatPearls. Published online 2023.
. Gale AJ. Current Understanding of Hemostasis. Toxicol Pathol. 2011;39(1):273-280.
. Hall JE, Hall ME. Guyton and Hall Text Book of Medical Physiology. 14th ed. Elsevier; 2021.
. Garmo C, Burns B. Physiology, Clotting Mechanism. StatPearls. Published online 2018.
. Fountain JH, Lappin SL. Physiology, Platelet. StatPearls. Published online 2025.
. Villani M, Ageno W, Grandone E, Dentali F. The prevention and treatment of venous thromboembolism in pregnancy. Expert Rev Cardiovasc Ther. 2017;15(5):397-402.
. Moiz B. A Review of Hemostasis in Normal Pregnancy and Puerperium. Natl J Heal Sci. 2017;2(3):123-127.
. Thornton P, Douglas J. Coagulation in pregnancy. Best Pract Res Clin Obstet Gynaecol. 2010;24(3):339-352.
. Langer AL, Connell NT. Update on pregnancy-associated venous thromboembolism. Thromb Updat. 2022;8:1-7.
. Jay RM, Lui P. How anticoagulants work. Tech Reg Anesth Pain Manag. 2006;10(2):30-39.
. Oduah EI, Linhardt RJ, Sharfstein ST. Heparin: Past, present, and future. Pharmaceuticals. 2016;9(3):1-12.
. Favaloro EJ, Pasalic L, Lippi G. Unfractionated heparin: optimizing laboratory monitoring and reducing unwanted interference in everyday hemostasis test practice. Polish Arch Intern Med. 2024;134(3):1-9.
. Ball CM, Featherstone PJ. The history of heparin. Anaesth Intensive Care. Published online 2024.
. Wiebe EM, Stafford AR, Fredenburgh JC, Weitz JI. Mechanism of catalysis of inhibition of factor IXa by antithrombin in the presence of heparin or pentasaccharide. J Biol Chem. 2003;278(37):35767-35774.
. Spadarella G, Di Minno A, Donati MB, Mormile M, Ventre I, Di Minno G. From unfractionated heparin to pentasaccharide: Paradigm of rigorous science growing in the understanding of the in vivo thrombin generation. Blood Rev. 2020;39:1-13.
. Olson S. Molecular mechanisms of antithrombin-heparin regulation of blood clotting proteinases. Biochemie. 2010;92(11):1587-1596.
. Setiabudy RD. Hemostasis Dan Trombosis. 6th ed. Badan Penerbit Fakultas Kedokteran Universitas Indonesia; 2018.
. Yu S, Chi Y, Ma X, Li X. Heparin in sepsis: current clinical findings and possible mechanisms. Front Immunol. 2024;15:1-15.
. Hirsh J, Raschke R. Heparin and low-molecular-weight heparin: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest. 2004;126:188-203.
. Amerali M, Politou M. Tinzaparin—a review of its molecular profile, pharmacology, special properties, and clinical uses. Eur J Clin Pharmacol. 2022;78(10):1555-1565.
. Kasthuri RS, Glover SL, Jonas W, et al. PF4/heparin-antibody complex induces monocyte tissue factor expression and release of tissue factor positive microparticles by activation of FcγRI. Blood. 2012;119(22):5285-5293.
. Gajic-Veljanoski O, Phua CW, Shah PS, Cheung AM. Effects of Long-Term Low-Molecular-Weight Heparin on Fractures and Bone Density in Non-Pregnant Adults: A Systematic Review With Meta-Analysis. J Gen Intern Med. 2016;31(8):947-957.
. Stevens SM, Woller SC, Baumann Kreuziger L, et al. Antithrombotic Therapy for VTE Disease: Compendium and Review of CHEST Guidelines 2012-2021. Chest. 2024;166(2):388-404.
. Vandiver JW, Vondracek TG. Antifactor xa levels versus activated partial thromboplastin time for monitoring unfractionated heparin. Pharmacotherapy. 2012;32(6):546-558.
. Koster A, Ljajikj E, Faraoni D. Traditional and non-traditional anticoagulation management during extracorporeal membrane oxygenation. Ann Cardiothorac Surg. 2019;8(1):129-136.
. May JE, Siniard RC, Taylor LJ, Marques MB, Gangaraju R. From Activated Partial Thromboplastin Time to Antifactor Xa and Back Again. Am J Clin Pathol. 2022;157(3):321-327.
. Patel P, Varacallo MA. Low-Molecular-Weight Heparin (LMWH). StatPearls. Published online 2025.
. Anggraini, D., Maani, H., & Rofinda, Z. D. (2018). Coagulation activity and D-dimer in sepsis patients. Indonesian journal of clinical pathology and medical laboratory, 24(2), 151-154.
. Jaspers TCC, Keyany A, Maat B, Meijer K, van den Bemt PMLA, Khorsand N. Therapeutically dosed low molecular weight heparins in renal impairment: a nationwide survey. Eur J Clin Pharmacol. 2022;78(9):1469-1479.
. Bauersachs RM. Fondaparinux Sodium: Recent Advances in the Management of Thrombosis. J Cardiovasc Pharmacol Ther. 2023;28:1-14.
. Hao Z, Jin DY, Stafford DW, Tie JK. Vitamin K-dependent carboxylation of coagulation factors: Insights from a cell-based functional study. Haematologica. 2020;105(8):2164-2173.
. Rishavy MA, Hallgren KW, Wilson L, Singh S, Runge KW, Berkner KL. Warfarin alters Vitamin K metabolism: a surprising mechanism of VKORC1 uncoupling necessitates an additional reductase. Blood. 2018;131(25):2826-2835.
. James AH. Pregnancy-associated thrombosis. Hematology. Published online 2009:277-285.
. Devis P, Knuttinen MG. Deep venous thrombosis in pregnancy: Incidence, pathogenesis and endovascular management. Cardiovasc Diagn Ther. 2017;7(3):300-319.
. Meng K, Hu X, Peng X, Zhang Z. Incidence of venous thromboembolism during pregnancy and the puerperium: A systematic review and meta-analysis. J Matern Neonatal Med. 2015;28(3):245-253.
. Hwang HG, Lee JH, Bang SM. Incidence of Pregnancy-Associated Venous Thromboembolism: Second Nationwide Study. Thromb Haemost. 2022;123(9):904-910.
. James AH. Review Thrombosis in Pregnancy and Maternal Outcomes. Birth Defect Res. 2015;105:159-166.
. Raia-Barjat T, Edebiri O, Chauleur C. Venous Thromboembolism Risk Score and Pregnancy. Front Cardiovasc Med. 2022;9:1-8.
. Royal College of Obstetricians and Gynaecologists. Reducing the Risk of Venous Thromboembolism during Pregnancy and the Puerperium Green-top Guideline No. 37a. 2015;(37):1-40.
. Bates SM, Rajasekhar A, Middeldorp S, et al. American Society of Hematology 2018 guidelines for management of venous thromboembolism: Venous thromboembolism in the context of pregnancy. Blood Adv. 2018;2(22):3317-3359.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2026 Rudy Afriant, Zulherman
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
