Generic placeholder image

Current Drug Therapy

Editor-in-Chief

ISSN (Print): 1574-8855
ISSN (Online): 2212-3903

Review Article

Oral Factor Xa (FXa) Inhibitors for Treatment of Heparin-induced Thrombocytopenia (HIT)

Author(s): Nicholas Munafo*, Sagar Patel, Kristine C. Willett and Amanda Morrill

Volume 16, Issue 2, 2021

Published on: 10 December, 2020

Page: [126 - 132] Pages: 7

DOI: 10.2174/1574885515999201210213348

Price: $65

Abstract

Background: Heparin is the most commonly used injectable anticoagulant for many indications, ranging from the treatment of atrial fibrillation to the prevention of clotting in patients undergoing surgery. Currently, only argatroban and bivalirudin are FDA approved for the management of heparin induced thrombocytopenia (HIT) in the United States, both of which are direct thrombin inhibitors. The agents being reviewed, apixaban and rivaroxaban, are oral direct factor Xa (FXa) inhibitors. Currently, neither has FDA approval for use in HIT. The objective of this review is to summarize the current evidence available regarding the use of oral factor Xa inhibitors for the treatment of HIT.

Methods: A literature search was conducted using Medline and Ovid Embase. Search terms included heparin-induced thrombocytopenia, HIT, apixaban, rivaroxaban, Xa Inhibitor, direct thrombin inhibitor, NOAC, and DOAC. Studies and case reports were included if they evaluated the efficacy and safety of oral FXa inhibitors for the treatment of HIT. Additional literature and case reports were found through bibliographic review.

Results and Discussion: Currently, available literature includes an in vitro study with apixaban, case reports, and retrospective and prospective cohort studies. The in vitro study evaluated the interaction between apixaban and platelets in the presence of HIT antibodies, which assessed its potential for use in HIT management. Fourteen case reports and one case series were also identified, of which six described treatment with apixaban and eight with rivaroxaban. Lastly, four cohort studies were published evaluating the use of direct acting oral anticoagulants (DOACs), including oral factor Xa inhibitors in patients with HIT. Although there are no published randomized control trials evaluating the use of FXa inhibitors in the management of HIT, there are several findings that may guide clinicians on the use of these agents in practice.

Conclusion: As indicated by the case reports, case series and cohort studies detailing clinical use and described in this manuscript, there are data and positive patient outcomes that support the potential use of these agents for HIT, and are an impetus for future studies.

Keywords: Anticoagulant, heparin induced thrombocytopenia, HIT, DOAC, factor Xa, apixaban, rivaroxaban.

Graphical Abstract

[1]
Hirsh J, Anand SS, Halperin JL, Fuster V. Mechanism of action and pharmacology of unfractionated heparin. Arterioscler Thromb Vasc Biol 2001; 21(7): 1094-6.
[http://dx.doi.org/10.1161/hq0701.093686] [PMID: 11451734]
[2]
Greinacher A. Heparin-induced thrombocytopenia. J Thromb Haemost 2009; 7(Suppl. 1): 9-12.
[http://dx.doi.org/10.1111/j.1538-7836.2009.03385.x] [PMID: 19630757]
[3]
Lovecchio F. Heparin-induced thrombocytopenia. Clin Toxicol (Phila) 2014; 52(6): 579-83.
[http://dx.doi.org/10.3109/15563650.2014.917181] [PMID: 24844576]
[4]
Ahmed I, Majeed A, Powell R. Heparin induced thrombocytopenia: diagnosis and management update. Postgrad Med J 2007; 83(983): 575-82.
[http://dx.doi.org/10.1136/pgmj.2007.059188] [PMID: 17823223]
[5]
Cuker A, Arepally GM, Chong BH, et al. American Society of Hematology 2018 guidelines for management of venous thromboembolism: heparin-induced thrombocytopenia. Blood Adv 2018; 2(22): 3360-92.
[http://dx.doi.org/10.1182/bloodadvances.2018024489] [PMID: 30482768]
[6]
Pfizer Inc. Argatroban, US physician prescribing information. 2019. Available from: http://labeling.pfizer.com/ShowLabeling.aspx?id=4601 (Cited: 1 June 2021).
[7]
Joseph L, Casanegra AI, Dhariwal M, et al. Bivalirudin for the treatment of patients with confirmed or suspected heparin-induced thrombocytopenia. J Thromb Haemost 2014; 12(7): 1044-53.
[http://dx.doi.org/10.1111/jth.12592] [PMID: 24766902]
[8]
Perdomo J, Leung HHL, Ahmadi Z, et al. Neutrophil activation and NETosis are the major drivers of thrombosis in heparin-induced thrombocytopenia. Nat Commun 2019; 10(1): 1322.
[http://dx.doi.org/10.1038/s41467-019-09160-7] [PMID: 30899022]
[9]
Janssen Pharmaceutical Companies. Xarelto, US physician prescribing information. 2021. Available from: https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/XARELTO-pi.pdf (Cited: 1 June 2021).
[10]
ARIXTRA. Research Triangle Park, NC; GlaxoSmithKline 2010.
[11]
Walenga JM, Prechel M, Hoppensteadt D, et al. Apixaban as an alternate oral anticoagulant for the management of patients with heparin-induced thrombocytopenia. Clin Appl Thromb Hemost 2013; 19(5): 482-7.
[http://dx.doi.org/10.1177/1076029613492876] [PMID: 23780399]
[12]
Larsen PB, Jørgensen M, Friis-Hansen L, Ingeberg S. Apixaban used for the management of heparin-induced thrombocytopenia in a 72-year-old woman with lung cancer. Clin Case Rep 2015; 3(12): 987-9.
[http://dx.doi.org/10.1002/ccr3.411] [PMID: 26732728]
[13]
Trujillo Agudelo D, Ramirez Quintero JD, Arango Barrientos M. Successful treatment of heparin-induced thrombocytopenia with apixaban in a patient with chronic kidney disease requiring hemodialysis. Clin Case Rep 2018; 6(11): 2147-9.
[http://dx.doi.org/10.1002/ccr3.1817] [PMID: 30455909]
[14]
Ezekwudo DE, Chacko R, Gbadamosi B, et al. Apixaban for treatment of confirmed heparin-induced thrombocytopenia: a case report and review of literature. Exp Hematol Oncol 2017; 6(1): 21.
[http://dx.doi.org/10.1186/s40164-017-0080-7] [PMID: 28725494]
[15]
Delgado-García G, Monreal-Robles R, Gallegos-Arguijo D, Marfil-Rivera J. [Apixaban as therapeutic option in nephropathy patients with heparin-induced thrombocytopenia (HIT)]. Gac Med Mex 2015; 151(6): 798-801.
[PMID: 26581538]
[16]
Khalid S, Daw H. The Role of Apixaban in the Treatment of Heparin-Induced Thrombocytopenia. Cureus 2017; 9(7): e1428.
[http://dx.doi.org/10.7759/cureus.1428] [PMID: 28884054]
[17]
Samoš M, Bolek T, Škorňová I, et al. Apixaban: a novel agent to treat heparin induced thrombocytopenia and to prevent embolism in patient with atrial fibrillation after multiple valve replacement? J Thromb Thrombolysis 2019; 48(4): 619-22.
[http://dx.doi.org/10.1007/s11239-019-01910-0] [PMID: 31264059]
[18]
Abouchakra L, Khabbaz Z, Abouassi S, Badaoui G. Rivaroxaban for treatment of heparin-induced thrombocytopenia after cardiac surgery: A case report. J Thorac Cardiovasc Surg 2015; 150(2): e19-20.
[http://dx.doi.org/10.1016/j.jtcvs.2015.04.054] [PMID: 26055438]
[19]
Casan JM, Grigoriadis G, Chan N, Chunilal S. Rivaroxaban in treatment refractory heparin-induced thrombocytopenia. BMJ Case Rep 2016; 2016: bcr2016216110.
[http://dx.doi.org/10.1136/bcr-2016-216110] [PMID: 27520997]
[20]
Hantson P, Lambert C, Hermans C. Rivaroxaban for arterial thrombosis related to heparin-induced thrombocytopenia. Blood Coagul Fibrinolysis 2015; 26(2): 205-6.
[http://dx.doi.org/10.1097/MBC.0000000000000205] [PMID: 25255239]
[21]
Tardy-Poncet B, Piot M, Montmartin A, Burdier A, Chalayer E, Tardy B. Delayed-onset heparin-induced thrombocytopenia without thrombosis in a patient receiving postoperative thromboprophylaxis with rivaroxaban. Thromb Haemost 2015; 114(3): 652-4.
[http://dx.doi.org/10.1160/TH14-07-0593] [PMID: 26062524]
[22]
Sartori M, Favaretto E, Cini M, Legnani C, Cosmi B. Rivaroxaban in the treatment of heparin-induced thrombocytopenia. J Thromb Thrombolysis 2015; 40(3): 392-4.
[http://dx.doi.org/10.1007/s11239-015-1208-4] [PMID: 25804370]
[23]
Manji F, Warkentin TE, Sheppard JI, Lee A. Fondaparinux cross-reactivity in heparin-induced thrombocytopenia successfully treated with high-dose intravenous immunoglobulin and rivaroxaban. Platelets 2020; 31(1): 124-7.
[http://dx.doi.org/10.1080/09537104.2019.1652263] [PMID: 31397594]
[24]
Vavlukis M, Kotlar I, Taravari H, Poposka L, Kedev S. Can rivaroxaban be a drug of choice for treating heparin-induced thrombocytopenia in a patient with pulmonary thromboembolism? Anatol J Cardiol 2017; 18(1): 77-9.
[http://dx.doi.org/10.14744/AnatolJCardiol.2017.7805] [PMID: 28680014]
[25]
Huang H, Lin Y, Yao RX, He MQ, Lin XJ. Successful treatment of severe heparin-induced thrombocytopenia with intravenous immunoglobulin, platelet transfusion and rivaroxaban: a case report. Chin Med Sci J 2019; 34(1): 60-4.
[http://dx.doi.org/10.24920/003462] [PMID: 30961783]
[26]
Ng HJ, Than H, Teo EC. First experiences with the use of rivaroxaban in the treatment of heparin-induced thrombocytopenia. Thromb Res 2015; 135(1): 205-7.
[http://dx.doi.org/10.1016/j.thromres.2014.06.005] [PMID: 24974053]
[27]
Sharifi M, Bay C, Vajo Z, Freeman W, Sharifi M, Schwartz F. New oral anticoagulants in the treatment of heparin-induced thrombocytopenia. Thromb Res 2015; 135(4): 607-9.
[http://dx.doi.org/10.1016/j.thromres.2015.01.009] [PMID: 25613925]
[28]
Kunk PR, Brown J, McShane M, Palkimas S, Gail Macik B. Direct oral anticoagulants in hypercoagulable states. J Thromb Thrombolysis 2017; 43(1): 79-85.
[http://dx.doi.org/10.1007/s11239-016-1420-x] [PMID: 27632140]
[29]
Davis KA, Davis DO. Direct acting oral anticoagulants for the treatment of suspected heparin-induced thrombocytopenia. Eur J Haematol 2017; 99(4): 332-5.
[http://dx.doi.org/10.1111/ejh.12921] [PMID: 28672052]
[30]
Agnelli G, Buller HR, Cohen A, et al. Oral apixaban for the treatment of venous thromboembolism in cancer patients: results from the AMPLIFY trial. J Thromb Haemost 2015; 13(12): 2187-91.
[http://dx.doi.org/10.1111/jth.13153] [PMID: 26407753]
[31]
Bauersachs R, Berkowitz SD, Brenner B, et al. EINSTEIN Investigators. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med 2010; 363(26): 2499-510.
[http://dx.doi.org/10.1056/NEJMoa1007903] [PMID: 21128814]
[32]
Linkins LA, Warkentin TE, Pai M, et al. Rivaroxaban for treatment of suspected or confirmed heparin-induced thrombocytopenia study. J Thromb Haemost 2016; 14(6): 1206-10.
[http://dx.doi.org/10.1111/jth.13330] [PMID: 27061271]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy