Pemantauan Penggunaan Antikoagulan terhadap Perubahan Nilai aPTT pada Pasien Kardiovaskuler
Abstract
Antikoagulan merupakan obat pengencer darah untuk mencegah pembentukan dan perkembangan trombus pada aliran darah. Warfarin dan heparin termasuk antikoagulan generasi lama. Rivaroxaban, edoksaban, dabigatran, dan apiksaban termasuk antikoagulan generasi baru. Obat ini memerlukan monitor yang ketat karena berindeks terapi sempit, dan memiliki potensi efek samping obat berupa perdarahan. Tujuan penelitian ini untuk mengetahui pengaruh penggunaan antikoagulan terhadap perubahan nilai aPTT dan mengetahui adanya kejadian adverse drug reaction (ADR) pada pasien kardiovaskuler di RSUD Prof. Dr. Margono Soekarjo Purwokerto. Metode penelitian ini dilakukan dengan rancangan deskriptif observational retrospektif, serta pengumpulan data didapat dari data rekam medis pasien rawat inap penyakit kardiovaskuler. Hasil penelitian ini menunjukkan bahwa responden paling banyak terdiagnosis miokard infark sebesar 39,9%, berusia 20–60 tahun (44%) dan paling banyak berjenis kelamin laki-laki (69,8%). Penggunaan antikoagulan yang digunakan pada responden penelitian ini, antara lain: heparin i.v. (64,70%), warfarin oral (14,11%), fondaparinux i.v. (18,86%), rivaroxaban oral (1,17%), dan enoxaparin oral (1,17%). Kejadian ADR yang timbul pada pasien yang menggunakan antikoagulan UFH mengalami hematuria (56,52%), epistaksis (13,04%), melena (13,04%), batuk berdarah (8,7%), hematemesis (4,35%), dan gusi berdarah (4,35%). Sedangkan pasien yang menggunakan antikoagulan fondaparinux mengalami hematuria (66,67%), epistaksis (11,11%), hematemesis (11,11%), dan gusi berdarah (11,11%). Hasil paired t-test menunjukkan terdapat pengaruh perubahan nilai aPTT setelah penggunaan antikoagulan heparin (p<0,05), dan kejadian ADR antikoagulan yang paling banyak timbul adalah hematuria. Penggunaan antikoagulan heparin dapat mengubah nilai aPTT sehingga perlu adanya monitoring tanda gejala perdarahan lebih lanjut.
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Chadalavada V, Venkata G, Mounika N, Veera V, Saikiran V, Sai G, et al. Drug Utilization Evaluation And Assessment Of Economic Burden Of Anticoagulants In A Tertiary Care Hospital In South India. J Pharm Sci Innov. 2018;7(5):188–94.
Daud M, Ahmad A, Banu N. Anticoagulant Drug Utilization Pattern And Their Cost Analysis : A Retrospective Study From Saudi Arabia. Journal of Pharmaceutical Health Services Research. 2020;11;411–414.
Di Nisio M, van Es N, Büller HR. Deep vein thrombosis and pulmonary embolism. Lancet. 2016;388(10063):3060–73.
Gregson J, Kaptoge S, Bolton T, Pennells L, Willeit P, Burgess S, et al. Cardiovascular Risk Factors Associated With Venous Thromboembolism. JAMA Cardiology. 2019;4(2):163–173.
Heuvel JM Van Den, Hövels AM, Büller HR, Boer A De. NOACs replace VKA as Preferred Oral Anticoagulant Among New Patients : A Drug Utilization Study In 560 Pharmacies In The Netherlands. Thrombosis Journal. 2018;16(7):1–10.
Whitworth, M.M., Haase, K.K., Fike, D.S., Young, R.B., dan Maclaughlin, E.J. Utilization And Prescribing Patterns Of Direct Oral Anticoagulants. International Journal of General Medicine. 2017;10;87–94.
Jaffer IH, Weitz JI. Antithrombotic drug. In: Hoffman R, Benz EJ, Silberstein LE, Heslop HE, Weitz JI, Anastasi J, et al., editors. Hematology. 7th ed. Amsterdam: Elsevier; 2018. p. 2168–88.
Queensland Health. Anticoagulant guideline for hospitalised adult patients. Brisbane: State of Queensland Government; 2022. p. 74.
Perhimpunan Dokter Spesialis Kardiovaskular Indonesia (PERKI). Pedoman tatalaksana sindrom koroner akut. Edisi IV. Jakarta: PERKI; 2018.
Hernaningsih Y, Maulidan EB. Examination of laboratory for monitoring heparin anticoagulant therapy. In: IntechOpen. London: IntechOpen; 2016. Available from: https://www.intechopen.com/books/advanced-biometric-technologies/liveness-detection-in-biometrics.
Whitman-Purves E, Wang L, Smith LM, Jones B. Performance of anti-factor Xa versus activated partial thromboplastin time for heparin monitoring using multiple nomograms. Clin Appl Thromb Hemost. 2018;24(2):310–6.
Sankhi S, Marasine NR, Thapa P, Dangi NB. Anticoagulant utilization and cost analysis among cardiology inpatients in a tertiary care teaching hospital of Western Nepal. Adv Pharmacol Pharm Sci. 2020;2020:1–6.
Kusumawaty, J., Hidayat, N., dan Ginanjar, E. Hubungan Jenis Kelamin Dengan Intensitas Hipertensi Pada Lansia di Wilayah Kerja Puskesmas Lakbok Kabupaten Ciamis. Jurnal Mutiara Medika. 2016;16(2):46–51.
Millett ERC, Peters SAE, Woodward M. Sex differences in risk factors for myocardial infarction: cohort study of UK Biobank participants. BMJ. 2018;363:k4247.
Ilic I, Ilic M. Risk factors for myocardial infarction in women and men: a case-control study. Biol Life Sci Forum. 2021;9(13):7–12.
Amrullah S, Harun RC, Bela DD, Try WA. Faktor resiko penyakit infark miokard akut di Rumah Sakit Umum Dewi Sartika Kota Kendari. J Ilm Karya Kesehatan. 2022;2(2):21–9.
DiDomenico RJ, Dobesh PP, Finks SW. Acute coronary syndrome. In: DiPiro JT, Yee GC, Posey LM, Haines ST, Nolin TD, Ellingrod V, editors. Pharmacotherapy: A Pathophysiologic Approach. 11th ed. New York: McGraw-Hill Education; 2020. p. 265–300.
Violi F, Soliman EZ, Pignatelli P, Pastori D. Atrial fibrillation and myocardial infarction: a systematic review and appraisal of pathophysiologic mechanisms. J Am Heart Assoc. 2016;5(5):e003347.
Lee HY, Yang PS, Kim TH, Uhm JS, Pak HN, Lee MH. Atrial fibrillation and the risk of myocardial infarction: a nationwide propensity-matched study. Sci Rep. 2017;7:1–8.
Lim HS, Willoughby SR, Schultz C, Gan C, Alasady M, Lau DH. Effect of atrial fibrillation on atrial thrombogenesis in humans: impact of rate and rhythm. J Am Coll Cardiol. 2013;61(8):852–60.
Göbel K, Eichler S, Wiendl H, Chavakis T, Kleinschnitz C, Meuth SG. The coagulation factors fibrinogen, thrombin, and factor XII in inflammatory disorders—a systematic review. Front Immunol. 2018;9:1731.
Onwordi EN, Gamal A, Zaman A. Anticoagulant therapy for acute coronary syndromes. Interv Cardiol Rev. 2018;13:87–92.
Setiadi AP, Halim SV. Penyakit kardiovaskular: Seri Pengobatan Rasional. Yogyakarta: Graha Ilmu; 2018.
Hindricks G, Potpara T, Dagres N, Arbelo E, Bax JJ, Blomström-Lundqvist C, et al. 2020 ESC guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J. 2021;42(5):373–498.
Perhimpunan Dokter Spesialis Kardiovaskular Indonesia (PERKI). Pedoman tata laksana fibrilasi atrium. Jakarta: PERKI; 2019. p. 54–5.
Kementerian Kesehatan Republik Indonesia. Laporan riset kesehatan dasar (RISKESDAS). Jakarta: Badan Penelitian dan Pengembangan Kesehatan; 2018.
Obas V, Vasan RS. The aging heart. Clin Sci. 2018;132(13):1367–82.
Virani SS, Alonso A, Aparicio HJ, Benjamin EJ, Bittencourt MS, Callaway CW, et al. Heart disease and stroke statistics—2021 update: a report from the American Heart Association. Circulation. 2021;143(8):e254–743.
Khaznadar AAJ, Wahid SR. Impact of age on risk factors and clinical manifestations of acute coronary syndrome: observations from the coronary care unit of Sulaimani. Hosp Pract Res. 2020;5(1):28–34.
Simanungkalit AP, Supit AI. Karakteristik dan perjalanan penyakit pasien infark miokard akut dengan elevasi segmen ST (IMA-EST) tanpa tatalaksana reperfusi pada rumah sakit perifer. Intisari Sains Medis. 2022;13(1):148–52.
Leentjens J, Peters M, Esselink AC, Smulders Y, Kramers C. Initial anticoagulation in patients with pulmonary embolism: thrombolysis, unfractionated heparin, LMWH, fondaparinux, or DOACs? Br J Clin Pharmacol. 2017;83(11):2356–66.
Zehnder JL. Drugs used in disorders of coagulation. In: Katzung BG, editor. Basic & Clinical Pharmacology. 14th ed. New York: McGraw-Hill; 2018.
Toulon P, Smahi M, De Pooter N. APTT therapeutic range for monitoring unfractionated heparin therapy. J Thromb Haemost. 2021;19(8):2002–6.
Syam F, Rahmadani S, Rustam R. Gambaran penggunaan obat pada pasien rawat inap infark miokard akut (IMA) di UPT RSUD Nene Mallomo. J Pharm Health Res. 2022;3(2):70–4.
Patel S, Singh R, Preuss CV. Warfarin [Updated 2022 Mar 13]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 [cited 2025 Jul 21]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK470313/
Leong R, Chu DK, Crowther MA. Direct oral anticoagulants after bariatric surgery—what is the evidence? J Thromb Haemost. 2022;20:1988–2000.
Nutescu EA, Burnett A, Fanikos J, Spinler S, Wittkowsky A. Pharmacology of anticoagulants used in the treatment of venous thromboembolism. J Thromb Thrombolysis. 2016;41(1):15–31.
Yokobus Y. New oral anticoagulants for atrial fibrillation. J Kedokteran Kesehatan Indones. 2017;8(2):102–9.
Martin SS, Aday AW, Almarzooq ZI, et al. 2024 heart disease and stroke statistics: a report of US and global data from the American Heart Association. Circulation. 2024;149:e347–913.
Tahaineh L, Gharaibeh S, Gharaibeh M. Evaluating unfractionated heparin fixed dosing protocol and establishing an institutional therapeutic range for UFH in hospital setting in Jordan. Clin Appl Thromb Hemost. 2014;20(1):73–7.
Perhimpunan Dokter Spesialis Kardiovaskular Indonesia (PERKI). Pedoman tata laksana sindrom koroner akut. Edisi V. Jakarta: PERKI; 2024.
De Luca L, Uguccioni M, Natale E, Pugliese M, Terranova A, Biffani E, et al. Effectiveness of fondaparinux vs unfractionated heparin following percutaneous coronary intervention in survivors of out-of-hospital cardiac arrest due to acute myocardial infarction. Eur J Clin Pharmacol. 2021;77(10):1563–7.
Kelleni M, editor. Anticoagulation Drugs: the Current State of the Art. London: IntechOpen; 2020. Available from:https://www.intechopen.com/books/8700
Merck Manuals. Warfarin [Internet]. Treasure Island (FL): Merck Manuals; 2022 [cited 2025 Jul 21]. Available from: https://www.merckmanuals.com/.
Patel S, Singh R, Preuss CV, Patel N. Warfarin. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 [cited 2025 Jul 21]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK470313/
Gechlik A, Espinosa J, Lucerna A, Patel K. A brief literature review on heparin: to bolus or not to bolus, that is the question. Strat Campus Res Day. 2022;1(1):1–2.
Octasari PM, Silvianingsih N. Kesesuaian nilai INR (international normalized ratio) pasien kardiovaskuler dengan terapi warfarin di Poli Spesialis Jantung RS Roemani Muhammadiyah Semarang. Cendekia J Pharm. 2022;6(1):46–54.
Shikdar S, Vashisht RBP. International normalized ratio (INR) [Internet]. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2023 [cited 2025 Jul 21]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK507707/
Katzung BG, Biaggioni I. Basic & Clinical Pharmacology. 14th ed. New York: McGraw-Hill; 2015.
Kim JS, Song JY, Moon KW, et al. Monitoring of unfractionated heparin using activated partial thromboplastin time: an assessment of the current nomogram and analysis according to age. Clin Appl Thromb Hemost. 2014;20(7):723–8.
Puspitasari AD, Suharjono, Yogiarto. Pengaruh lama pemberian fondaparinux terhadap activated partial thromboplastin time (APTT) pada pasien sindroma koroner akut. J Farm Ilmu Kefarm Indones. 2018;5(2):99–106.
Kearon C, Johnston M, Moffat K, McGinnis J, Ginsberg JS. Effect of warfarin on activated partial thromboplastin time in patients receiving heparin. Arch Intern Med. 1998;158(10):1140–3.
Perry DJ. A practical guide to haemostasis [Internet]. United Kingdom: Sang Medicine; 2024 [cited 2025 Jul 21]. Available from: https://practical-haemostasis.com
Santoro RC, Molinari AC, Leotta M, Martini T. Isolated prolongation of activated partial thromboplastin time: not just bleeding risk! Medicina (Kaunas). 2023;59(6):1169.
Thygesen K, Alpert JS, Jaffe AS, Chaitman BR, et al. Fourth universal definition of myocardial infarction. Eur Heart J. 2018;40:237–69.
Carreras ET, Mega JL. Role of oral anticoagulants in patients after an acute coronary syndrome. Arterioscler Thromb Vasc Biol. 2015;35(3):520–4.
Gaurav K, Khan MY, Ponde CK, Kumar VF. Fondaparinux: a cornerstone drug in acute coronary syndrome. World J Cardiol. 2022;14(1):40–53.
Nesheiwat Z, Goyal A, Jagtap M. Atrial fibrillation [Updated 2025 Mar 25]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 [cited 2025 Jul 21]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK526072/
Capranzano P, Angiolillo DJ. Antithrombotic management of elderly patients with coronary artery disease. JACC Cardiovasc Interv. 2021;14(7):723–38.
Mateti UV, Rajakannan T, Nekkanti H, Rajesh V, Mallaysamy S, Ramachandran P. Drug–drug interactions in hospitalized cardiac patients. J Young Pharm. 2015;3(4):329–33.
Antoniewicz AA, Zdanowski R, Bogacki R, et al. Macroscopic hematuria—a leading urological problem in patients on anticoagulant therapy: is the common diagnostic standard still advisable? ISRN Urol. 2013;2013:1–5.
Alomar MJ. Factors affecting the development of adverse drug reactions. Saudi Pharm J. 2014;22(2):83–94.
DOI: https://doi.org/10.15416/ijcp.2025.v14i2.49454
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