Use of Lepirudin in Patients with Heparin-Induced Thrombocytopenia and Renal Failure Requiring Hemodialysis

Dager, William E.; White, Richard

doi:10.1345/aph.10282

Cited by 30 publications

(14 citation statements)

References 15 publications

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“…Maintenance dosing using intermittent boluses was utilized according to clinical response (aPTT, assessment of further bleeding or thrombotic episodes, and recovery of end-organ function). A report 13 published subsequent to our experience using lepirudin for systemic anticoagulation in renal failure confirms our findings of conservative dosing with frequent monitoring to avoid excessive anticoagulation. Any dosing strategy requires intensive monitoring to avoid excessive or inadequate anticoagulation in this population.…”

Section: Discussionsupporting

confidence: 84%

Tackling the Devastating Effects of Heparin‐Induced Thrombocytopenia

Abraham

Uber

Lazarchick

et al. 2002

Congestive Heart Failure

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Heparin‐induced thrombocytopenia with associated thrombosis is a potentially catastrophic complication of heparin therapy. Heart failure patients often require heparin therapy in the setting of multiple comorbidities, particularly renal insufficiency. The authors report a case of heparin‐induced thrombocytopenia with associated thrombosis in a patient with multisystem organ failure and discuss dosing regimens using lepirudin for the treatment of this disorder. The potential risk for excessive anticoagulation is highlighted and a conservative dosing strategy with frequent monitoring of this agent in the presence of renal failure is emphasized.

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Section: Discussionsupporting

confidence: 84%

Tackling the Devastating Effects of Heparin‐Induced Thrombocytopenia

Abraham

Uber

Lazarchick

et al. 2002

Congestive Heart Failure

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“…In publications describing two relatively contemporary HIT registries in the United States, the race of the patients treated using alternative anticoagulation either was not reported [15], or was reported together with clinical results only for the overall population [16,17]. Although some case reports describe nonwhite patients with HIT treated using alternative anticoagulation [18][19][20][21][22][23][24][25], anticoagulant responses and clinical outcomes remain to be better differentiated among African Americans, Asians, and Hispanics.…”

Section: Introductionmentioning

confidence: 99%

Dosing patterns and outcomes in African American, Asian, and Hispanic patients with heparin-induced thrombocytopenia treated with argatroban

Hursting

Jang

2008

J Thromb Thrombolysis

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We retrospectively evaluated dosing patterns and 37-day outcomes in argatroban-treated African American (n = 52), Asian (n = 13), and Hispanic (n = 14) patients with heparin-induced thrombocytopenia (HIT). The Asians required a lesser median dose (1.0 microg/kg/min) than the other groups (1.9 microg/kg/min, each) to achieve comparable activated partial thromboplastin times (medians: 61-69 s). Durations of therapy were similar (medians: 4.0-5.5 days). New thrombosis occurred in 11 (21%) African Americans, 1 (8%) Asian, and 1 (7%) Hispanic; of these 13 patients, 9 (69%) had baseline HIT-related thrombosis. Amputation occurred in 6 (12%) African Americans and 3 (21%) Hispanics; of these nine patients, 6 (67%) had diabetes. One (2%) African American and 1 (7%) Hispanic died from thrombosis. The composite of death due to thrombosis, amputation due to ischemic complications of HIT, or new thrombosis occurred in 14 (27%) African Americans, 1 (8%) Asian, and 4 (29%) Hispanics. Two (4%) African Americans and none others (0%) had major bleeding. These findings suggest that despite argatroban anticoagulation, African Americans and Hispanics may have worse outcomes in HIT than Asians. In minority patients with adverse HIT outcomes, baseline HIT-related thrombosis or diabetes is often present.

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“…A second patient suffering from ARF likewise developed HIT, so anticoagulation was changed from UFH to lepirudin. 41 Continuous infusion of lepirudin at a dose of 0.005 to 0.008 mg/kg ϫ hour without a bolus resulted in a stable aPTT prolongation of 45 to 60 seconds. Hemodialysis again was performed with a polysulfone high-flux hemodialyzer membrane with prevention of clotting by the same means as described earlier.…”

Section: Hirudin In End-stage Renal Diseasementioning

confidence: 94%

“…One ESRD patient with acute HIT first received a continuous IV infusion of 0.01 mg/kg ϫ hour lepirudin without prior bolus dose targeting an aPTT range of 50 to 70 seconds (2 to 2.5 times the control). 41 Anticoagulation with lepirudin at a maintenance dose of 0.015 mg/kg ϫ hour resulted in stable prolongation of the aPTT to 60 seconds. Hemodialysis was performed using a polysulfone high-flux hemodialyzer membrane.…”

Section: Hirudin In End-stage Renal Diseasementioning

confidence: 99%

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Hirudin In Renal Insufficiency

Fischer¹

2002

Semin Thromb Hemost

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Recombinant hirudins (r-hirudins) are potent direct thrombin inhibitors increasingly used for alternative anticoagulation, especially in heparin-induced thrombocytopenia. R-hirudins are almost exclusively eliminated by the kidneys, and a close correlation between r-hirudin clearance and endogenous creatinine clearance has been observed. Accordingly, the pharmacokinetics of r-hirudin are altered in patients with renal insufficiency. A decline of renal r-hirudin clearance is associated with an increase of r-hirudin half-life and the area under the curve (AUC). Therefore, renal impairment necessitates reduction of r-hirudin dose to avoid overdose or inadequate accumulation of the thrombin inhibitor. To this end, close monitoring of r-hirudin anticoagulation is required, which at best is performed by measuring r-hirudin blood levels by ecarin clotting times (ECT) or chromogenic assays, in addition to activated partial thromboplastin time (aPTT). Recent studies showed that r-hirudin anticoagulation is feasible in acute or chronic renal failure treated with continuous or intermittent renal replacement therapy, if appropriate r-hirudin dosing and adequate monitoring are warranted. High-volume hemofiltration with r-hirudin-permeable hemodialyzers constitutes a valuable means to markedly reduce r-hirudin blood concentration and total r-hirudin body content in case of r-hirudin overdose or r-hirudin-associated bleeding. In the future, the hepatically eliminated direct thrombin inhibitor argatroban may facilitate alternative anticoagulation in patients with renal insufficiency.

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Use of Lepirudin in Patients with Heparin-Induced Thrombocytopenia and Renal Failure Requiring Hemodialysis

Abstract: In patients with renal failure who develop HIT, lepirudin is one available alternative to heparin despite its poor renal elimination pattern and subsequently prolonged half-life.

Cited by 30 publications

References 15 publications

Tackling the Devastating Effects of Heparin‐Induced Thrombocytopenia

Tackling the Devastating Effects of Heparin‐Induced Thrombocytopenia

Dosing patterns and outcomes in African American, Asian, and Hispanic patients with heparin-induced thrombocytopenia treated with argatroban

Hirudin In Renal Insufficiency

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