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

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.

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.

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

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 Direct Thrombin Inhibitor Resistance and Possible Mechanisms

2016 ◽  
Vol 51 (11) ◽  
pp. 922-927 ◽  
Author(s):  
Maria Cardinale ◽  
Michael Ha ◽  
Michael H. Liu ◽  
David P. Reardon
Keyword(s):  
International Normalized Ratio ◽  
Resistance Mechanisms ◽  
Direct Thrombin Inhibitor ◽  
Thrombin Inhibitors ◽  
Thrombin Inhibitor ◽  
Direct Thrombin Inhibitors ◽  
Heparin Induced Thrombocytopenia ◽  
Vein Thrombosis ◽  
Inhibitor Resistance ◽  
Deep Vein

Objective To report 3 cases in which doses of bivalirudin higher than commonly used in clinical practice were required in order to achieve therapeutic anticoagulation as monitored by the activated partial thromboplastin time (aPTT). Case Summary The medical records of 3 patients who required large doses of bivalirudin to remain therapeutic were thoroughly reviewed. In all 3 patients, bivalirudin was initiated at a rate appropriate for the patients' renal function and titrated using a nurse-driven protocol with recommended dose adjustments based on aPTT. Indications for bivalirudin were anticoagulation in intra-aortic balloon pump, treatment of deep vein thrombosis, and heparin-induced thrombocytopenia with thrombosis. Target aPTT was achieved between 25.5 and 134 hours after initiation despite appropriate titration intervals per protocol. Discussion Bivalirudin is a direct thrombin inhibitor frequently used off-label for the medical management of heparin-induced thrombocytopenia. It typically exhibits predictable, dose-dependent anticoagulation. Heparin-induced thrombocytopenia was suspected in 2 of the 3 cases and confirmed in 1. In all 3 patients, target aPTT was initially achieved with doses between 0.456 and 1.0 mg/kg/h after a median of 30.7 hours; up to 1.8 mg/kg/h was required to maintain therapeutic aPTT. In 2 of the cases, the international normalized ratio also increased unexpectedly upon achievement of therapeutic aPTT values. Conclusion Direct thrombin inhibitors may be subject to resistance mechanisms similar to those previously described in patients receiving heparin. The anticoagulation status of these patients remains unknown.

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.

The direct thrombin inhibitor hirudin

2008 ◽  
Vol 99 (11) ◽  
pp. 819-829 ◽  
Author(s):  
Theodore Warkentin ◽  
Andreas Greinacher
Keyword(s):  
Side Effects ◽  
Acute Coronary Syndromes ◽  
Clinical Applications ◽  
Direct Thrombin Inhibitor ◽  
Thrombin Inhibitor ◽  
Heparin Induced Thrombocytopenia ◽  
Package Inserts ◽  
The Third ◽  
Preventative Measures ◽  
Coronary Syndromes

SummaryThis review discusses the pharmacology and clinical applications of hirudin, a bivalent direct thrombin inhibitor (DTI). Besides the current major indication for hirudin – anticoagulation of patients with heparin-induced thrombocytopenia (HIT) – the experience with hirudin in other indications, especially acute coronary syndromes, are briefly presented. Hirudins have been formally studied prior to their regulatory approval; however, important information on their side effects and relevant preventative measures only became available later. Therefore, current recommendations and dosing schedules for hirudin differ considerably from the information given in the package inserts. Drawbacks of hirudin and important precautions for avoiding potential adverse effects are discussed in detail in the third part of this review.

Successful use of bivalirudin for cardiopulmonary bypass in a patient with heparin allergy

Perfusion ◽  
2007 ◽  
Vol 22 (1) ◽  
pp. 67-69 ◽  
Author(s):  
F. Pappalardo ◽  
A. Franco ◽  
G. Crescenzi G ◽  
A. Poli ◽  
A. Zangrillo ◽  
...  
Keyword(s):  
Cardiac Surgery ◽  
Cardiopulmonary Bypass ◽  
Half Life ◽  
Clinical Problem ◽  
Direct Thrombin Inhibitor ◽  
Thrombin Inhibitor ◽  
Heparin Induced Thrombocytopenia ◽  
Heparin Allergy ◽  
Anaphylactoid Reactions ◽  
Ige Mediated

Heparin-induced IgE-mediated hypersensitivity and anaphylactoid reactions, although rare, can pose a serious clinical problem for patients requiring cardiopulmonary bypass (CPB). Bivalirudin is a bivalent reversible direct thrombin inhibitor, with a half-life of 25 min, eliminated mostly by proteolytic cleavage. There are some reports on the use of bivalirudin for cardiac surgery, particularly for heparin-induced thrombocytopenia (HIT), but none on cases of heparin allergy. We report a case of heparin allergy successfully managed for CPB with bivalirudin anticoagulation. Perfusion (2007) 22, 67-69.

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