Prolonged half‐life of argatroban in patients with renal dysfunction and antiphospholipid antibody syndrome being treated for heparin‐induced thrombocytopenia

Abstract

Argatroban is a direct thrombin inhibitor approved for the treatment of heparin‐induced thrombocytopenia (HIT) type II. Argatroban is predominantly metabolized in the liver. It is widely believed that no dosage adjustment is required in patients with renal insufficiency, making it a preferred agent in patients on renal replacement therapy (Reddy and Grossman, Ann Pharm 2005;39:1601–1605). The elimination half‐life of argatroban is ∼50 min. Lupus anticoagulants can cause baseline elevation of the PTT and hence it is difficult to monitor the effects of anticoagulants such as heparin, lepirudin, or argatroban in patients with antiphospholipid antibody syndrome. Heparin levels may be used as an alternative for heparin monitoring but plasma levels of argatroban are not commercially available. A chromogenic antifactor IIa assay could be useful for monitoring argatroban in the presence of a lupus anticoagulant, but it is not widely available at present. We report a patient with end‐stage renal disease, maintained on peritoneal dialysis with HIT, who demonstrated a markedly prolonged half‐life when treated with argatroban despite the discontinuation of therapy. This case also demonstrates the lack of guidelines for the monitoring of argatroban therapy in the presence of an underlying lupus anticoagulant. Am. J. Hematol., 2008. © 2007 Wiley‐Liss, Inc.

American Society of Hematology 2018 guidelines for management of venous thromboembolism: heparin-induced thrombocytopenia

“…We identified nonrandomized studies evaluating the use of argatroban, danaparoid, fondaparinux, bivalirudin, and rivaroxaban. Ten studies reported on treatment with argatroban, [111][112][113][114][115][116][117][118][119][120] 3 studies reported on treatment with danaparoid, 70,121,122 3 studies reported on treatment with fondaparinux, [123][124][125] 2 studies reported on treatment with bivalirudin, 57,126 and 1 study reported on treatment with rivaroxaban. 127 These studies reported on the outcomes of bleeding, thromboembolic events, mortality, and serious adverse events.…”

Clinical Experience with Argatroban for Heparin-Induced Thrombocytopenia in a Large Teaching Hospital

“…1,7,22 The literature suggests that a lower dose may be required for patients who have undergone cardiac surgery and for those with multiple organ system failure, heart failure, severe anasarca, or conditions associated with hepatic congestion. 1,26,27 The most common causes of hepatic congestion are volume overload and any cause of right-sided heart failure (constrictive pericarditis, mitral stenosis, tricuspid regurgitation, cor pulmonale, or cardiomyopathy). 26,28 Recent reports of argatroban use for a variety of clinical indications and in various clinical settings have reported lower doses (0.5-1.2 µg/kg per minute) to achieve target aPTT.…”

“…1,26,27 The most common causes of hepatic congestion are volume overload and any cause of right-sided heart failure (constrictive pericarditis, mitral stenosis, tricuspid regurgitation, cor pulmonale, or cardiomyopathy). 26,28 Recent reports of argatroban use for a variety of clinical indications and in various clinical settings have reported lower doses (0.5-1.2 µg/kg per minute) to achieve target aPTT. 1 The evidence suggests that critically ill patients may require lower doses of argatroban.…”

“…34 Several reports, each describing a small number of patients, have reported the use of argatroban in patients requiring renal replacement therapy. [16][17][18][19]21,26,31,[35][36][37][38][39][40][41][42] Dialytic clearance of argatroban with high-flux membranes has been suggested to be clinically insignificant, with systemic clearance increased by about 20%. 36,37 Many authors have reported using doses less than 0.5 µg/kg per minute to achieve aPTT of 40-80 s, but some of the patients were critically ill, with acute changes in liver function or recent cardiovascular surgery, or they may have had volume overload, with subsequent hepatic congestion.…”

Les inhibiteurs directs de la thrombine, l’hirudine, la bivalirudine, l’argatroban, et le dabigatran etexilate

“…Elle est indiquée chez les patients adultes atteints de thrombopénie induite par l'héparine sans insuffisance rénale [27].…”