Medical treatment of acute deep venous thrombosis and pulmonary embolism
Peter Gloviczki, Michael C. Dalsing, Bo Eklöf, Fedor Lurie, Thomas W. Wakefield, Monika L. Gloviczki in Handbook of Venous and Lymphatic Disorders, 2017
There are many agents in development for anticoagulation, aiming to replace either LMWH or warfarin. Fondaparinux (Arixtra®, GlaxoSmithKline), a synthetic pentasaccharide that has an antithrombin sequence identical to heparin, targets factor Xa. Fondaparinux has been approved for the treatment of DVT and PE when administered in conjunction with warfarin, for thrombosis prophylaxis in patients with total hip replacement, total knee replacement, and hip fracture, and in patients undergoing abdominal surgery. Fondaparinux, administered subcutaneously, has a 17-hour half-life and dosage is based on body weight. It exhibits no endothelial or protein binding, and importantly does not produce thrombocytopenia. No antidote is readily available for this agent. In VTE prophylaxis, a meta-analysis involving more than 7000 patients demonstrated a greater than 50% risk reduction in VTE using fondaparinux begun 6 hours after surgery compared to LMWH begun 12–24 hours after surgery.12 Although major bleeding was increased, critical bleeding was not increased. Fondaparinux has also been found to be effective in the prophylaxis of other groups of patients, including general medical patients.13 For the treatment of VTE, fondaparinux was found to be equal to standard heparin and LMWH for DVT and for PE.13,14 Fondaparinux has also been found to be effective for the treatment of superficial thrombophlebitis over a 45-day course of treatment at a prophylactic dose (level of evidence: 2B).2,15
Primary PCI In St-Elevation Myocardial Infarction
Debabrata Mukherjee, Eric R. Bates, Marco Roffi, Richard A. Lange, David J. Moliterno, Nadia M. Whitehead in Cardiovascular Catheterization and Intervention, 2017
The use of intravenous unfractionated heparin (UFH) for adjunctive anticoagulation in primary PCI during STEMI is currently the most common approach. Enoxaparin and fondaparinux have also been studied in this setting. The ATOLL (Acute STEMI Treated with Primary PCI and IV Enoxaparin or UFH to Lower Ischemic and Bleeding Events at Short- and Long-term Follow-up) trial compared intravenous enoxaparin 0.5 mg/kg with UFH titrated to ACT levels during primary PCI.44 The trial was statistically underpowered and the primary endpoint of mortality, MI, procedure failure, or major bleeding was negative. Although the trial showed decreased mortality with enoxaparin, it did not reduce infarct size or bleeding risk, or improve TIMI flow. In the absence of a clear explanation for decreased mortality, it is likely that results were due to chance. Fondaparinux has been associated with catheter thrombosis and should not be relied on as the sole anticoagulant during primary PCI.45
Adjunctive pharmacotherapy and coronary intervention
Ever D. Grech in Practical Interventional Cardiology, 2017
Fondaparinux is a synthetic analogue of the heparin pentasaccharide that causes an anti-thrombin-mediated, selective inhibition of Factor Xa; its effect is exclusively on factor Xa with no action on thrombin. It can be administered subcutaneously with a time to peak effect of 2.5 hours and a half-life of approximately 20 hours in patients with normal renal function, which allows for predictable anticoagulant effects with once daily dosing. The foundation for its use comes from two large randomised clinical trials for the treatment of ACS, which included patients treated with PCI. The OASIS-5 trial, in which approximately 40% of patients underwent PCI, found NSTE ACS patients treated with fondaparinux had non-inferior rates of the composite endpoint (death, MI or refractory ischaemia) at 9 and 30 days; however, the fondaparinux treatment group had significantly lower rates of major bleeding (2.4% vs. 5.1%, p < .00001) when compared with enoxaparin, with or without adjunctive GPI. At 6 months fondaparinux produced a significant reduction in all major endpoints; however, in the subset of patients who underwent PCI there was no difference in the primary endpoint at any time point.48
Belgian clinical guidance on anticoagulation management in hospitalised and ambulatory patients with COVID-19
Published in Acta Clinica Belgica, 2022
Thomas Vanassche, Christelle Orlando, Kristel Vandenbosch, Alain Gadisseur, Cédric Hermans, Kristin Jochmans, Jean-Marc Minon, Serge Motte, Harlinde Peperstraete, Pierre Péters, Muriel Sprynger, Patrizio Lancellotti, Isabelle Dehaene, Patrick Emonts, Christophe Vandenbriele, Peter Verhamme, Cécile Oury
Low molecular weight heparin (LMWH) is the recommended therapy for pharmacological thromboprophylaxis in critically ill patients, with the exception of patients with severe renal dysfunction (for whom unfractionated heparin could be considered based on a careful risk/benefit assessment) and patients with a history of heparin-induced thrombocytopenia [24,25]. In the latter, fondaparinux is an alternative drug for the prevention or treatment of thrombosis, although it is not reimbursed for hospitalised patients in Belgium. Several experimental antivirals used to treat COVID-19 may increase plasma levels of direct oral anticoagulant (DOAC) because of P-glycoprotein inhibition and/or competition, inhibition or induction of CYP3A4-dependent pathways [26]. Therefore, parenteral LMWH is the preferred agent for thromboprophylaxis [26]. Although interim guidelines agree on the choice of thromboprophylaxis, the optimal anticoagulant dose in COVID-19 in patients is unknown; intermediate- or full-dose regimens rather than prophylactic doses have been suggested but higher doses also cause more bleeding [3,27].
Heparin-induced thrombocytopenia: pathophysiology, diagnosis and treatment
Published in Expert Review of Hematology, 2021
Anne-Mette Hvas, Emmanuel J Favaloro, Maja Hellfritzsch
Fondaparinux is a synthetic pentasaccharide also possessing an antithrombin-dependent inhibition of factor Xa. Fondaparinux is approved for prophylaxis and treatment of venous thromboembolism. Although it has not been approved for treatment in HIT, it has been used off-label for this indication for the past 20 years. Only observational evidence exists for the use of fondaparinux in the context of HIT. The evidence was summarized in a systematic review by Linkins et al., including nine observational studies, of which seven studies were retrospective, including in total 154 patients with laboratory confirmed HIT [57]. Overall, rates of thrombosis, bleeding and death supported fondaparinux as an effective and safe treatment option in HIT patients [57]. The major shortcomings of fondaparinux is a long half-life and renal elimination leading to a contraindication in patients with creatinine clearance below 30 mL/min, which is challenging in critically ill patients. Besides, potential cross-reactivity with HIT-antibodies also exists [58].
Clinical safety of low-dose anticoagulation with fondaparinux in patients undergoing peripheral endovascular treatment due to critical limb-threatening ischaemia – a pilot study
Published in Acta Cardiologica, 2021
Sorin Giusca, Michael Lichtenberg, Christoph Eisenbach, Grigorios Korosoglou
The mean follow-up duration was 11.8 ± 1.2 months. During follow-up, clinically significant bleeding occurred in 3 patients (13%) of the fondaparinux arm versus 5 patients (21%) of the control arm (p = ns). In addition, target vessel revascularisation occurred in three patients and major amputation was performed in one patient of the fondaparinux arm (n = 4; 17%), versus five patients who received target vessel revascularisation and one patient who underwent major amputation in the control arm (n = 6; 25%, p = ns). No clinically relevant bleeding occurred within the first month of follow-up during medication of the patients with fondaparinux and DAPT. The corresponding Kaplan–Meier curves are provided in Figure 1(A,B).
Related Knowledge Centers
- Anticoagulant
- Antithrombin
- Deep Vein Thrombosis
- Enoxaparin Sodium
- Platelet Factor 4
- Streptokinase
- Pulmonary Embolism
- Low-Molecular-Weight Heparin
- Heparin-Induced Thrombocytopenia
- Direct Factor Xa Inhibitors