Search results for "antithrombin"
showing 10 items of 53 documents
The control of anti-coagulation in acute dialyses with sensitive laboratory parameters.
1992
In seven patients who had to be dialysed between four and 13 times due to acute renal failure, low molecular weight heparin (LMWH) Fragmin was used for anticoagulation. According to dose-finding studies, 80-90 U kg-1 body weight of LMWH as a single bolus were administered initially, producing dose-related levels of 0.3-1.5 anti-factor Xa U ml-1 in plasma. Apart from the anti-Xa activity in the plasma, the thrombin anti-thrombin III complex (TAT complex) and a fibrin degradation product (D-dimer) were measured as parameters of a coagulation activation. A sufficient anti-coagulation during dialysis was supposed to exist at a normal range (5.0 micrograms l-1 or below) of TAT complex. Pathologi…
Antagonizing dabigatran by idarucizumab in cases of ischemic stroke or intracranial hemorrhage in Germany - A national case collection.
2017
BackgroundIdarucizumab is a monoclonal antibody fragment with high affinity for dabigatran that reverses its anticoagulant effects within minutes. It may exhibit the potential for patients under dabigatran therapy suffering ischemic stroke to regain eligibility for thrombolysis with rt-PA and may inhibit lesion growth in patients with intracerebral hemorrhage on dabigatran.AimsTo provide insights into the clinical use of idarucizumab in patients under effective dabigatran anticoagulation presenting with signs of ischemic stroke or intracranial hemorrhage.MethodsRetrospective data collected from German neurological/neurosurgical departments administering idarucizumab following product launch…
Anticoagulation with argatroban for elective percutaneous coronary intervention: population pharmacokinetics and pharmacokinetic-pharmacodynamic rela…
2010
The synthetic direct thrombin inhibitor argatroban has a rapid onset and offset of anticoagulation. However, there are no data about the pharmacokinetic-pharmacodynamic (PK-PD) relationship of argatroban in patients undergoing contemporary percutaneous coronary intervention (PCI) and no data about other coagulation parameters than activated clotting time (ACT) in this setting. In the ARG-E04-trial, 140 patients were randomly assigned to argatroban (250, 300, or 350 μg/kg as bolus before PCI, followed by 15, 20, or 25 μg/kg/min infusion) or unfractionated heparin (70-100 IU/kg bolus). A 2-compartment model with first-order elimination adequately described the pharmacokinetic profile of argat…
Mapping the fluorophilicity of a hydrophobic pocket: synthesis and biological evaluation of tricyclic thrombin inhibitors directing fluorinated alkyl…
2006
In the completion of our fluorine scan of tricyclic inhibitors to map the fluorophilicity/fluorophobicity of the thrombin active site, a series of 11 new ligands featuring alkyl, alkenyl, and fluoroalkyl groups was prepared to explore fluorine effects on binding into the hydrophobic proximal (P) pocket, lined by Tyr 60A and Trp 60D, His 57, and Leu 99. The synthesis of the tricyclic scaffolds was based on the 1,3-dipolar cycloaddition of azomethine ylides, derived from L-proline and 4-bromobenzaldehyde, with N-(4-fluorobenzyl)maleimide. Introduction of alkyl, alkenyl, and partially fluorinated alkyl residues was achieved upon substitution of a sulfonyl group by mixed Mg/Zn organometallics f…
Scalable Bio Marker Combinations for Early Stroke Diagnosis: A Systematic Review
2021
Background: Acute stroke treatment is a time-critical process in which every minute counts. Laboratory biomarkers are needed to aid clinical decisions in the diagnosis. Although imaging is critical for this process, these biomarkers may provide additional information to distinguish actual stroke from its mimics and monitor patient condition and the effect of potential neuroprotective strategies. For such biomarkers to be effectively scalable to public health in any economic setting, these must be cost-effective and non-invasive. We hypothesized that blood-based combinations (panels) of proteins might be the key to this approach and explored this possibility through a systematic review.Metho…
Predicting and Tuning Physicochemical Properties in Lead Optimization: Amine Basicities
2007
This review describes simple and useful concepts for predicting and tuning the pK(a) values of basic amine centers, a crucial step in the optimization of physical and ADME properties of many lead structures in drug-discovery research. The article starts with a case study of tricyclic thrombin inhibitors featuring a tertiary amine center with pK(a) values that can be tuned over a wide range, from the usual value of around 10 to below 2 by (remote) neighboring functionalities commonly encountered in medicinal chemistry. Next, the changes in pK(a) of acyclic and cyclic amines upon substitution by fluorine, oxygen, nitrogen, and sulfur functionalities, as well as carbonyl and carboxyl derivativ…
Increased thrombin generation and complement activation in patients with type IIA hyperlipoproteinemia: effects of simvastatin treatment
1997
Abstract The aim of this study was to demonstrate the existence of increased thrombin generation and complement activation in patients with type IIa primary hyperlipoproteinemia, but no signs of atherosclerotic vascular disease and to assess the effects of simvastatin treatment in these patients. We studied 40 patients with type IIa primary hyperlipoproteinemia and 40 healthy subjects matched for sex, age, body mass index, and smoking status. The study was divided into two phases. In the first phase, a cross-sectional comparison of lipid and hemostatic patterns was performed between patients and controls. In the second phase, we assessed the effect of a persistent reduction in cholesterol s…
Effect of gemfibrozil treatment on fibrinolysis system in patients with hypertriglyceridemia
1992
Abstract The effect of gemfibrozil on lipidic, coagulative, and fibrinolytic pattern was studied in 20 patients with primary type IV hyperlipoproteinemia. After a 4-week stabilization period during which administration of lipid-lowering drugs was stopped and an isocaloric diet (20% protein, 30% fat, and 50% carbohydrates) was prescribed, 20 patients (12 men and 8 women; mean age, 38 ± 4 years; body mass index, 23.4 ± 1.5) suffering from primary hypertriglyceridemia were included in this study and treated for a 12-week period with gemfibrozil (600 mg BID). Every 4 weeks the following parameters were checked: glycemia, triglycerides, total cholesterol, high density lipoprotein-cholesterol, to…
High-Dose ϵ-Aminocaproic Acid Versus Aprotinin: Antifibrinolytic Efficacy in First-Time Coronary Operations
1998
The antifibrinolytic efficacy of a high-dose regimen of epsilon-aminocaproic acid (epsilon-ACA) was compared with aprotinin in first-time coronary operations.In a prospective, double-blinded, randomized study, 20 patients received high-dose epsilon-ACA (10 g both as a loading and cardiopulmonary bypass priming dose, 2.5 g/h until 4 hours after protamine), and another 20 patients received aprotinin (2 x 10(6) KIU [280 mg] for loading and priming, 0.5 x 10(6) KIU/h [70 mg/h]). Ten untreated patients served as controls.Both agents reduced postoperative levels of thrombin/antithrombin III complexes, D-dimers, fibrin degradation products, free plasma hemoglobin (epsilon-ACA versus aprotinin, p =…
Factor VIII and Antithrombin III in Atherosclerosis Obliterans of the Lower Limbs
1984
In the multifactorial pathogenesis of atherosclerosis (the W.H.O. gives a list of about forty risk factors) recent acquisitions have allowed to determine in part the role carried out by the term “haemocoagulative disorders” (90) showing the possible connections between haematic components of haemocoagulation and vascular wall that up to now have been only hypothesised.