scholarly journals A case of the atherothrombotic cerebral infarction showed progressing stroke after discontinuation of the direct thrombin inhibitor

Nosotchu ◽  
2015 ◽  
Vol 37 (6) ◽  
pp. 446-451 ◽  
Author(s):  
Eiko Higuchi ◽  
Yumiko Uchiyama ◽  
Mutsumi Iizima ◽  
Kazuo Kitagawa
Keyword(s):  
Cerebral Infarction ◽  
Direct Thrombin Inhibitor ◽  
Thrombin Inhibitor ◽  
Progressing Stroke ◽  
Atherothrombotic Cerebral Infarction

Anticoagulant Activity of Hirulog™, a Direct Thrombin Inhibitor, in Humans

1993 ◽  
Vol 69 (02) ◽  
pp. 157-163 ◽  
Author(s):  
Irving Fox ◽  
Adrian Dawson ◽  
Peter Loynds ◽  
Jane Eisner ◽  
Kathleen Findlen ◽  
...  
Keyword(s):  
Rational Design ◽  
Therapeutic Potential ◽  
Anticoagulant Activity ◽  
Subcutaneous Administration ◽  
Direct Thrombin Inhibitor ◽  
Controlled Study ◽  
Thrombin Inhibitor ◽  
Thrombin Time ◽  
Thrombotic Disease ◽  
Dose Dependent

SummaryHirulog™ (BG8967) is a direct thrombin inhibitor built by rational design using the protein hirudin as a model (Maraganore et al. [1990]; Biochemistry 29: 7095–101). In order to evaluate the therapeutic potential for hirulog in the management of thrombotic disease, the tolerability and anticoagulant activity of the agent were examined in a study of human volunteers.In a randomized, placebo-controlled study (n = 54), the intravenous infusion of hirulog over 15 min showed a rapid, dose-dependent prolongation of activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT). There was a corresponding dose-dependent increase in plasma hirulog levels. The peptide was rapidly cleared with a half-life of 36 min and a total body clearance rate for the peptide of 0.43 1 kg−1 h−1. Similar activity was observed following subcutaneous injection but with sustained pharmacodynamic and pharmacokinetic behavior. There was a significant correlation between pharmacokinetic and pharmacodynamic variables for both intravenous (r = 0.8, p <0.001) and subcutaneous administration (r = 0.7, p = 0.002).To evaluate the possible interactions of aspirin on the tolerability and anticoagulant activity of intravenous hirulog, a cross-over design was employed in eight subjects. Aspirin administration did not modify the peptide’s activity. At the administered dose of 0.6 mg kg−1 h−1 for 2 h, hirulog infusion prolonged APTT from 230 to 260% baseline. The infusion of hirulog in subjects who had received aspirin was not associated with any significant changes in the template bleeding time.The final phase of the study examined the activity and tolerability of hirulog in ten subjects during prolonged intravenous infusions for up to 24 h. The peptide (0.3 mg kg−1 h−1) exhibited sustained anticoagulant activity with no evidence for a cumulative effect. During hirulog infusion, APTT was prolonged from 210 to 250% baseline.In all phases of the study, hirulog administration was generally well-tolerated.Our observations show that hirulog is an active antithrombin agent with excellent tolerability in humans. As a direct thrombin inhibitor, hirulog provides a novel approach for the management of thrombotic disease.

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.

Effects of the direct thrombin inhibitor melagatran in rats with endotoxin-induced sepsis

2006 ◽  
Vol 23 (Supplement 37) ◽  
pp. 81
Author(s):  
N. Nitescu ◽  
E. Grimberg ◽  
S.-E. Ricksten ◽  
G. Guron
Keyword(s):  
Direct Thrombin Inhibitor ◽  
Thrombin Inhibitor

Alternative parenteral anticoagulation with argatroban, a direct thrombin inhibitor

2005 ◽  
Vol 3 (1) ◽  
pp. 31-41 ◽  
Author(s):  
Marian P LaMonte ◽  
Philip M Brown ◽  
Marcie J Hursting
Keyword(s):  
Direct Thrombin Inhibitor ◽  
Thrombin Inhibitor

Mitochondrial haplogroup A is a genetic risk factor for atherothrombotic cerebral infarction in Japanese females

Mitochondrion ◽  
2007 ◽  
Vol 7 (1-2) ◽  
pp. 72-79 ◽  
Author(s):  
Yutaka Nishigaki ◽  
Yoshiji Yamada ◽  
Noriyuki Fuku ◽  
Hitoshi Matsuo ◽  
Tomonori Segawa ◽  
...  
Keyword(s):  
Risk Factor ◽  
Cerebral Infarction ◽  
Genetic Risk ◽  
Genetic Risk Factor ◽  
Mitochondrial Haplogroup ◽  
Atherothrombotic Cerebral Infarction

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.

Sign in / Sign up

Export Citation Format

Share Document