Argatroban and Renal Replacement Therapy in Patients with Heparin-Induced Thrombocytopenia

2005 ◽  
Vol 39 (2) ◽  
pp. 231-236 ◽  
Author(s):  
Ignatius Y Tang ◽  
Donna S Cox ◽  
Kruti Patel ◽  
Bharathi V Reddy ◽  
Linda Nahlik ◽  
...  
Keyword(s):  
At Risk ◽  
Renal Replacement Therapy ◽  
Replacement Therapy ◽  
Direct Thrombin Inhibitor ◽  
Thrombin Inhibitor ◽  
Systemic Clearance ◽  
Recovery Method ◽  
P Values ◽  
Heparin Induced Thrombocytopenia ◽  
Alternative Anticoagulation

BACKGROUND: Argatroban, a direct thrombin inhibitor, is an effective anticoagulant for patients who have heparin-induced thrombocytopenia (HIT). Anticoagulation is usually required for renal replacement therapy (RRT). OBJECTIVE: To prospectively evaluate the pharmacokinetics, pharmacodynamics, and safety of argatroban during RRT in hospitalized patients with or at risk for HIT. METHODS: Five patients with known or suspected HIT underwent hemodialysis (n = 4) or continuous venovenous hemofiltration (CVVH, n = 1), while receiving a continuous infusion of argatroban 0.5–2 μg/kg/min. Activated partial thromboplastin times (aPTTs), activated clotting times (ACTs), argatroban concentrations (plasma, dialysate, CVVH effluent), and safety were assessed before, during, and after a 4-hour session of RRT. Systemic and dialytic argatroban clearances were calculated. RESULTS: Among the 4 hemodialysis patients, aPTT, ACT, and plasma argatroban concentrations remained stable during RRT, with respective mean ± SD values of 74.3 ± 34.2 seconds, 198 ± 23 seconds, and 499 ± 353 ng/mL before RRT, and 70.6 ± 21.4 seconds, 181 ± 12 seconds, and 453 ± 295 ng/mL 2 hours after starting RRT (p values NS). Systemic clearance was 17.7 ± 12.8 L/h before hemodialysis and 17.0 ± 9.5 L/h during hemodialysis (n = 2). The dialyzer clearance (dialysate recovery method) was 1.5 ± 0.4 L/h (n = 4). Generally similar responses occurred in the CVVH patient: systemic argatroban clearance was 4.8 L/h before CVVH and 4 L/h during CVVH. The hemofilter argatroban clearance was 0.9 L/h. No bleeding or thrombosis occurred. CONCLUSIONS: Argatroban provides effective alternative anticoagulation in patients with or at risk for HIT during RRT. Argatroban clearance by high-flux membranes during hemodialysis and CVVH is clinically insignificant, necessitating no dose adjustment.

Argatroban Anticoagulation in Patients with Heparin-Induced Thrombocytopenia Requiring Renal Replacement Therapy

2005 ◽  
Vol 39 (10) ◽  
pp. 1601-1605 ◽  
Author(s):  
Bharathi V Reddy ◽  
Eric J Grossman ◽  
Sharon A Trevino ◽  
Marcie J Hursting ◽  
Patrick T Murray
Keyword(s):  
Renal Failure ◽  
Renal Replacement Therapy ◽  
Replacement Therapy ◽  
Hepatic Impairment ◽  
Bleeding Risk ◽  
Repeated Administration ◽  
Adverse Outcomes ◽  
Thrombin Inhibitor ◽  
Multicenter Studies ◽  
Heparin Induced Thrombocytopenia

BACKGROUND: Argatroban, a direct thrombin inhibitor, is used for prophylaxis or treatment of thrombosis in heparin-induced thrombocytopenia (HIT). The recommended initial dose is 2 μg/kg/min (0.5 μg/kg/min in hepatic impairment), adjusted to achieve activated partial thromboplastin time (aPTT) values 1.5–3.0 times baseline. However, few argatroban-treated patients with HIT and renal failure requiring renal replacement therapy (RRT) have been described. OBJECTIVE: To evaluate the safety and efficacy of argatroban anticoagulation during RRT in patients with HIT. METHODS: We retrospectively reviewed records from 47 patients with HIT and renal failure requiring RRT who underwent 50 treatment courses with argatroban. Patients with HIT had received argatroban during prospective, multicenter studies. Outcomes, safety, and dosing information were summarized. RESULTS: In the multicenter experience, no patient died due to thrombosis and 2 (4%) patients developed new thrombosis while on argatroban. No adverse outcomes occurred during argatroban reexposure. Starting doses were typically 2 μg/kg/min in patients without hepatic impairment and <1.5 μg/kg/min in those with hepatic impairment. Median (range) infusion doses were 1.7 (0.2–2.8) and 0.7 (0.1–1.7) μg/kg/min, respectively, with associated median (range) aPTT ratios, relative to baseline, of 2.2 (1.6–3.6) and 2.0 (1.4–4.1), respectively. Major bleeding occurred in 3 (6%) of 50 treatment courses. CONCLUSIONS: Argatroban provides effective anticoagulation upon initial and repeated administration in patients with HIT and renal impairment requiring RRT, with an acceptably low bleeding risk. Current dosing recommendations are adequate for these patients.

scholarly journals Use of a Novel Bicarbonate-Based Impella 5.5 Purge Solution in a Coagulopathic Patient

2021 ◽  
Author(s):  
Kyle Simonsen ◽  
Brady Gunn ◽  
Amber Malhotra ◽  
Daniel Beckles ◽  
Michael Koerner ◽  
...  
Keyword(s):  
Artery Bypass ◽  
Direct Thrombin Inhibitor ◽  
Thrombin Inhibitor ◽  
Severe Bleeding ◽  
Heparin Induced Thrombocytopenia ◽  
Bypass Procedure ◽  
Life Saving ◽  
Pump Thrombosis ◽  
Alternative Anticoagulation ◽  
Severe Coagulopathy

The Impella 5.5 with SmartAssist (Abiomed; Danvers, MA) is a life-saving treatment option in acute heart failure which utilizes a continuous heparin purge solution to prevent thrombosis. In patients with contraindications to heparin, alternative anticoagulation strategies are required. We describe the stepwise management of anticoagulation in a coagulopathic patient with persistent cardiogenic shock following a coronary artery bypass procedure who underwent Impella 5.5 placement. A direct thrombin inhibitor-based purge solution was utilized while evaluating for heparin-induced thrombocytopenia. Use of a novel bicarbonate-based purge solution (BBPS) was successfully used due to severe coagulopathy. There were no episodes of pump thrombosis or episodes of severe bleeding on the BBPS and systemic effects of alkalosis and hypernatremia were minimal.

scholarly journals Development and validation of prediction models for mechanical ventilation, renal replacement therapy, and readmission in COVID-19 patients

2021 ◽  
Author(s):  
Victor Alfonso Rodriguez ◽  
Shreyas Bhave ◽  
Ruijun Chen ◽  
Chao Pang ◽  
George Hripcsak ◽  
...  
Keyword(s):  
At Risk ◽  
Mechanical Ventilation ◽  
Renal Replacement Therapy ◽  
Receiver Operating Characteristic ◽  
Replacement Therapy ◽  
Operating Characteristic ◽  
Prediction Models ◽  
External Validation ◽  
Electronic Health Record Data ◽  
Receiver Operating

Abstract Objective Coronavirus disease 2019 (COVID-19) patients are at risk for resource-intensive outcomes including mechanical ventilation (MV), renal replacement therapy (RRT), and readmission. Accurate outcome prognostication could facilitate hospital resource allocation. We develop and validate predictive models for each outcome using retrospective electronic health record data for COVID-19 patients treated between March 2 and May 6, 2020. Materials and Methods For each outcome, we trained 3 classes of prediction models using clinical data for a cohort of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2)–positive patients (n = 2256). Cross-validation was used to select the best-performing models per the areas under the receiver-operating characteristic and precision-recall curves. Models were validated using a held-out cohort (n = 855). We measured each model’s calibration and evaluated feature importances to interpret model output. Results The predictive performance for our selected models on the held-out cohort was as follows: area under the receiver-operating characteristic curve—MV 0.743 (95% CI, 0.682-0.812), RRT 0.847 (95% CI, 0.772-0.936), readmission 0.871 (95% CI, 0.830-0.917); area under the precision-recall curve—MV 0.137 (95% CI, 0.047-0.175), RRT 0.325 (95% CI, 0.117-0.497), readmission 0.504 (95% CI, 0.388-0.604). Predictions were well calibrated, and the most important features within each model were consistent with clinical intuition. Discussion Our models produce performant, well-calibrated, and interpretable predictions for COVID-19 patients at risk for the target outcomes. They demonstrate the potential to accurately estimate outcome prognosis in resource-constrained care sites managing COVID-19 patients. Conclusions We develop and validate prognostic models targeting MV, RRT, and readmission for hospitalized COVID-19 patients which produce accurate, interpretable predictions. Additional external validation studies are needed to further verify the generalizability of our results.

Safety and Efficacy of Argatroban in the Management of Heparin-Induced Thrombocytopenia

2011 ◽  
Vol 4 ◽  
pp. CMBD.S5118 ◽  
Author(s):  
Bernd Saugel ◽  
Roland M. Schmid ◽  
Wolfgang Huber
Keyword(s):  
Arterial Thrombosis ◽  
Pharmacokinetic Profile ◽  
The United States ◽  
Heparin Therapy ◽  
Direct Thrombin Inhibitor ◽  
Thrombin Inhibitor ◽  
Heparin Induced Thrombocytopenia ◽  
Safety And Efficacy ◽  
Increased Risk ◽  
Life Threatening

Heparin-induced thrombocytopenia (HIT) is a life-threatening adverse reaction to heparin therapy that is characterized by thrombocytopenia and an increased risk of venous and arterial thrombosis. According to guidelines, in patients with strongly suspected or confirmed HIT all sources of heparin have to be discontinued and an alternative, nonheparin anticoagulant for HIT treatment must immediately be started. For both the prophylaxis of thrombembolic events in HIT and the treatment of HIT with thrombosis the direct thrombin inhibitor argatroban is approved in the United States. The objective of this review is to describe the mechanism of action and the pharmacokinetic profile of argatroban, to characterize argatroban regarding its safety and therapeutic efficacy and to discuss its place in therapy in HIT.

scholarly journals Venous limb gangrene during overlapping therapy with warfarin and a direct thrombin inhibitor for immune heparin-induced thrombocytopenia

2002 ◽  
Vol 71 (1) ◽  
pp. 50-52 ◽  
Author(s):  
Maureen A. Smythe ◽  
Theodore E. Warkentin ◽  
Jennifer L. Stephens ◽  
Dana Zakalik ◽  
Joan C. Mattson
Keyword(s):  
Direct Thrombin Inhibitor ◽  
Thrombin Inhibitor ◽  
Heparin Induced Thrombocytopenia

Dabigatran Pharmacokinetics and Pharmacodynamics during Renal Replacement Therapy

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4734-4734
Author(s):  
Alison Martin ◽  
Rommel Tirona ◽  
Moist Louise ◽  
Alejandro Lazo-Langner
Keyword(s):  
Renal Replacement Therapy ◽  
Replacement Therapy ◽  
Pulmonary Hemorrhage ◽  
Kidney Injury ◽  
Thrombin Inhibitor ◽  
Blood Transfusions ◽  
Partial Recovery ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Perfusion Rate ◽  
Significant Change

Abstract Introduction: Dabigatran is an oral direct thrombin inhibitor approved for use in prevention and treatment of thromboembolism. There is currently no reliable strategy for reversing its anticoagulant effects. The use of activated prothrombin complex concentrates has been reported, however, the relationship between dabigatran concentration and anticoagulation parameters in this setting have not been formally assessed or documented. There are also few reports on the pharmacokinetics and pharmacodynamics of dabigatran in the context of renal replacement therapy. This report describes a case of dabigatran overdose and management with factor eight bypassing activity (FEIBA), and hemodialysis. Case Presentation: A 62-year-old man taking dabigatran 110 mg twice daily presented with hematemesis, shock, acute kidney injury, INR > 8 and PTT > 150 s, hemoglobin 104 g/L and creatinine 1675 µmol/L. Last dose of dabigatran was ingested within 10 hours of presentation. Additional complications included hematuria, pulmonary hemorrhage, gastrointestinal bleeding and cardiac arrest. The patient required multiple blood transfusions at presentation. In an attempt to reverse the anticoagulant effects of dabigatran, the patient received 42 units/kg of FEIBA. A dialysis catheter was placed approximately 2 hours later without complication. Conventional hemodialysis (CHD) was initiated for high clearances with blood flows of 200 mL/min over 4 hours, followed by continuous venovenous hemodialysis (CVVHD). No further blood transfusions were required following administration of dialysis. He had resolution of all hemorrhagic symptoms by day 5 and achieved partial recovery of kidney function. Dialysis was discontinued on day 3 and the patient was discharged to a rehabilitation facility on day 34. Results: Bloodwork drawn every 2 hours was analyzed for INR, PTT and dabigatran levels using HEMOCLOT® assay and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Two hours following FEIBA administration, INR and PTT decreased from 7.4 to 3.6 and 114 s to 100 s, respectively despite no significant change in dabigatran levels (1.26 µg/mL - 1.30 µg/mL). Plasma dabigatran half-lives were 5.4 hours during CHD, 28 hours with CVVHD and 65 hours post-dialysis. Dialytic clearance values for dabigatran were estimated with a pharmacometric model. Plasma dialysis clearance for CHD was 66 mL/min (plasma perfusion rate of 128 mL/min) while the plasma dialysis clearance for CVVHD was 20 mL/min (plasma perfusion rate of 101 mL/min). Conclusions: Information regarding management of dabigatran overdose is scarce. To the best of our knowledge, this is the first study to document the use of FEIBA in the acute management of dabigatran overdose with pharmacokinetic and pharmacodynamic testing. By use of HEMOCLOT® assay, we were able to demonstrate a rapid reversal of INR and PTT despite no significant change in dabigatran levels. This report supports the use of FEIBA for reversal of the anticoagulant effects of dabigatran for urgent procedures. This report also adds to literature demonstrating that dabigatran overdose should be initially treated with CHD rather than CVVHD. CHD with high flows and a high flux dialyzer is best, as it has greater efficiency of dabigatran clearance than CVVHD. Disclosures Lazo-Langner: Bayer: Honoraria; Pfizer: Honoraria.

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

Blood ◽  
2009 ◽  
Vol 113 (11) ◽  
pp. 2402-2409 ◽  
Author(s):  
Martina Tschudi ◽  
Bernhard Lämmle ◽  
Lorenzo Alberio
Keyword(s):  
Impaired Renal Function ◽  
Direct Thrombin Inhibitor ◽  
Thrombin Inhibitor ◽  
Single Center ◽  
Dosing Regimen ◽  
Heparin Induced Thrombocytopenia ◽  
Single Center Experience ◽  
Therapeutic Anticoagulation ◽  
D Dimer ◽  
Anticoagulation Intensity

The recommended dose (bolus 0.4 mg/kg followed by 0.15 mg/kg per hour) of lepirudin, a direct thrombin inhibitor licensed for treatment of heparin-induced thrombocytopenia (HIT), is too high. Starting in 2001, we omitted the bolus and reduced maintenance dose by at least one-third. Analyzing 53 HIT patients treated between January 2001 and February 2007, we observed that therapeutic anticoagulation intensity already 4 hours after lepirudin start had been reached with the following initial lepirudin doses (median): 0.078 mg/kg per hour [creatinine clearance (CrCl) more than 60 mL/min], 0.040 mg/kg per hour (CrCl 30-60 mL/min), and 0.013 mg/kg per hour (CrCl < 30 mL/min). The efficacy of this treatment was documented by increasing platelets and decreasing D-dimers. Based on this experience, we derived a lepirudin dosing regimen, which was prospectively evaluated treating 15 HIT patients between March 2007 and February 2008. We show that omitting the initial lepirudin bolus and administering 0.08 mg/kg per hour in patients with CrCl more than 60 mL/min, 0.04 mg/kg per hour in patients with CrCl 30-60 mL/min, and 0.01 to 0.02 mg/kg per hour in those with CrCl less than 30 mL/min is efficacious and safe, as documented by increasing platelet counts, decreasing D-dimer levels, and rare thrombotic (1 of 46) and major bleeding (4 of 46) complications.

scholarly journals Evaluation of a multi-target direct thrombin inhibitor dosing and titration guideline for patients with suspected heparin-induced thrombocytopenia

2015 ◽  
Vol 90 (8) ◽  
pp. E143-E145 ◽  
Author(s):  
James F. Gilmore ◽  
Christopher D. Adams ◽  
Rachel M. Blum ◽  
John Fanikos ◽  
Beth Anne Hirning ◽  
...  
Keyword(s):  
Direct Thrombin Inhibitor ◽  
Thrombin Inhibitor ◽  
Heparin Induced Thrombocytopenia
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