Lepirudin: is the approved dosing schedule too high?

Hacquard, Marie; Maistre, Emmanuel de; Lecompte, Thomas

doi:10.1111/j.1538-7836.2005.01620.x

Cited by 32 publications

(15 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recent publications have reported that lower doses may be sufficient. 6,8,9 In the present work, we show that omission of the initial bolus and a reduced lepirudin starting dose (0.08 mg/kg per hour for patients with normal renal function, 0.04 mg/kg per hour for patients with CrCl 30-60 mL/min, and 0.01-0.02 mg/kg per hour for those with CrCl Ͻ 30 mL/min) is efficacious and safe. This in-house dosing scheme was derived from the retrospective analysis of 53 HIT patients 10 and prospectively evaluated treating additional 15 consecutive HIT patients.…”

Section: Discussionsupporting

confidence: 53%

“…Three recent publications reporting that lower lepirudin doses than those officially recommended may be sufficient are in agreement with our observation; however, no experimentally established dosing regimen was proposed. 6,8,9 The aim of the present 2-phase study ("Patients") was to define an adequate in-house lepirudin dosing scheme for HIT patients with normal and variably decreased renal function. To the best of our knowledge, this is the first study to propose lepirudin dosing regimens for HIT patients with normal and moderately or severely impaired renal function, thus providing evidence for reduced lepirudin doses, as recently recommended by the American College of Chest Physicians (ACCP) panel.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Dosing lepirudin in patients with heparin-induced thrombocytopenia and normal or impaired renal function: a single-center experience with 68 patients

Tschudi

Lämmle

Alberio

2009

Blood

View full text Add to dashboard Cite

Section: Discussionsupporting

confidence: 53%

Section: Introductionmentioning

confidence: 99%

Dosing lepirudin in patients with heparin-induced thrombocytopenia and normal or impaired renal function: a single-center experience with 68 patients

Tschudi

Lämmle

Alberio

2009

Blood

View full text Add to dashboard Cite

“…Recent studies have also reported that the actual doses administered to HIT patients were lower than those recommended. 8,[10][11][12] The second main finding was that, within this low dose range, mean lepirudin dose was nevertheless not an independent predictive factor for thrombotic complications. In contrast, it was an independent predictive factor for major bleeding (the higher the dose, the higher the bleeding risk).…”

Section: Discussionmentioning

confidence: 99%

Predictive factors for thrombosis and major bleeding in an observational study in 181 patients with heparin-induced thrombocytopenia treated with lepirudin

Tardy

Lecompte

Boelhen

et al. 2006

Blood

View full text Add to dashboard Cite

The antithrombotic efficacy of lepirudin in patients with heparin-induced thrombocytopenia (HIT) is compromised by an increased risk for bleeding. A retrospective observational analysis in 181 patients (median age, 67 years) with confirmed HIT treated in routine practice with lepirudin was performed to identify predictive factors for thrombotic and bleeding complications. Lepirudin was administered at a mean (؎ SD) dose of 0.06 ؎ 0.04 mg/kg/h (compared with a recommended initial dose of 0.15 mg/kg/h). Mean activated partial thromboplastin time was greater than 1.5 times baseline value in 99.4% of patients. Median treatment duration was 7.7 days. Until discharge from the hospital, 13.8% and 20.4% of patients experienced a thrombotic or a major bleeding event, respectively. On multivariate analysis, mean lepirudin dose was not a significant predictive factor for thrombosis. In contrast, mean lepirudin dose greater than 0.07 mg/kg/h, long duration of lepirudin treatment, and moderate to severe renal impairment were significant positive factors for major bleeding. Overall, these results suggest that the recommended dose of lepirudin in patients with HIT is too high; the use of reduced doses may be safer with regard to bleeding risk and does not compromise antithrombotic efficacy. (Blood.

show abstract

“…32 Retrospective studies show that use of lower doses than those recommended by the manufacturer are associated with less bleeding and without compromised efficacy. 33,34 Thus, current trends are to avoid the initial lepirudin bolus, and to start with a lower infusion rate (0.05 to 0.10 mg/kg/hr). Monitoring of the aPTT should continue at 4-hour intervals until it is clear that the aPTT is within the therapeutic range and stable (no longer rising).…”

Section: Two Diagnosticsmentioning

confidence: 99%

Think of HIT

Warkentin¹

2006

Hematology

104

View full text Add to dashboard Cite

/L in 90% of patients, most of whom evince a 50% or greater fall in the platelet count. HIT that begins after stopping heparin ("delayed-onset HIT") is increasingly recognized. Factors influencing risk of HIT include type of heparin (unfractionated heparin > low-molecular-weight heparin), type of patient (surgical > medical), and gender (female > male). Since timely diagnosis and treatment of HIT may reduce the risk of adverse outcomes, this review focuses on those clinical circumstances that should prompt the clinician to "think of HIT." Coumarin anticoagulants such as warfarin are ineffective in acute HIT and can even be deleterious by predisposing to microthrombosis via protein C depletion (venous limb gangrene and skin necrosis syndromes). Thus, it is important to avoid or postpone coumarin while managing HIT hypercoagulability, focusing on agents that inhibit thrombin directly (lepirudin, argatroban) or that inhibit its generation (danaparoid, ?fondaparinux). Post-marketing experience suggests that standard dosing of lepirudin is too high; current recommendations are to avoid the initial lepirudin bolus and to begin with lower infusion rates, even in patients without overt renal dysfunction.

show abstract

Lepirudin: is the approved dosing schedule too high?

Cited by 32 publications

References 10 publications

Dosing lepirudin in patients with heparin-induced thrombocytopenia and normal or impaired renal function: a single-center experience with 68 patients

Dosing lepirudin in patients with heparin-induced thrombocytopenia and normal or impaired renal function: a single-center experience with 68 patients

Predictive factors for thrombosis and major bleeding in an observational study in 181 patients with heparin-induced thrombocytopenia treated with lepirudin

Think of HIT

Contact Info

Product

Resources

About