Pharmacodynamics assessment of Bemiparin after multiple prophylactic and single therapeutic doses in adult and elderly healthy volunteers and in subjects with varying degrees of renal impairment.

Abstract:

INTRODUCTION:Aging and renal impairment may prolong the half-life and lead to accumulation of low molecular weight heparins. Correct dosing is critical to prevent bleeding or thrombosis. MATERIALS AND METHODS:Open, parallel study. Healthy adult [n=13] and elderly (>65yrs) [n=12] volunteers; and subjects with mild (ClCr≥50 to ≤80mL/min, n=8), moderate (ClCr≥30 to <50mL/min, n=7), and severe (ClCr<30mL/min, n=8) renal impairment received four prophylactic doses (3,500IU/24h) and a single therapeutic dose (115IU/kg) of bemiparin with an interim washout period. Anti-FXa activity and the potential need for dose adjustment were evaluated. RESULTS:There were statistically significant differences in the severe renal impairment group vs. adult volunteers in all anti-FXa related parameters, but no significant differences in any of the anti-FXa related parameters between the adult and the elderly. Anti-FXa simulations after 10 prophylactic doses predicted mean Amax=0.59IU/mL in subjects with severe renal impairment and 0.33-0.39IU/mL in the rest. Simulations in the severe renal impairment group with dose adjustment (2,500IU/24h) predicted all individual Amax<0.60IU/mL (mean Amax=0.42IU/ml). Simulations after 10 therapeutic doses predicted mean Amax=1.22IU/mL in severe renal impairment group and 0.89-0.98IU/mL in the rest. Simulations in the severe renal impairment group with 75% dose adjustment predicted individual Amax≤1.60IU/mL (mean Amax=0.91IU/mL). CONCLUSIONS:No dose adjustments are required in elderly with preserved renal function. A dose adjustment of bemiparin is only advisable in patients with severe renal impairment when using prophylactic or therapeutic doses.

journal_name

Thromb Res

journal_title

Thrombosis research

authors

Rico S,Antonijoan RM,Ballester MR,Gutierro I,Ayani I,Martinez-Gonzalez J,Borrell M,Fontcuberta J,Gich I

doi

10.1016/j.thromres.2014.03.038

subject

Has Abstract

pub_date

2014-06-01 00:00:00

pages

1029-38

issue

6

eissn

0049-3848

issn

1879-2472

pii

S0049-3848(14)00168-6

journal_volume

133

pub_type

杂志文章,多中心研究
  • Certoparin versus UFH to prevent venous thromboembolic events in the very elderly patient: an analysis of the CERTIFY study.

    abstract:INTRODUCTION:There is an exponential rise of thromboembolic risk with age because of co-morbidities, immobility and pharmacotherapy. We aimed to investigate the benefits and risks of heparin prophylaxis in very elderly patients ≥80 years and the type of heparin used in a subgroup analysis of the CERTIFY trial. PATIENT...

    journal_title:Thrombosis research

    pub_type: 杂志文章,随机对照试验

    doi:10.1016/j.thromres.2011.05.002

    authors: Schellong SM,Gerlach HE,Tebbe U,Haas S,Melzer N,Abletshauser C,Sieder C,Bramlage P,Riess H,Bauersachs R

    更新日期:2011-11-01 00:00:00

  • Long-term treatment of venous thromboembolism with tinzaparin compared to vitamin K antagonists: a meta-analysis of 5 randomized trials in non-cancer and cancer patients.

    abstract:PURPOSE:Due to its specific pharmacokinetic profile, tinzaparin, a low-molecular-weight heparin (LMWH), appears not to be associated with anti-factor Xa accumulation. Our meta-analysis aimed at determining whether long-term curative doses of tinzaparin is a valuable alternative to vitamin K antagonists (VKA) for the tr...

    journal_title:Thrombosis research

    pub_type: 杂志文章,meta分析

    doi:10.1016/j.thromres.2012.08.290

    authors: Laporte S,Bertoletti L,Romera A,Mismetti P,Pérez de Llano LA,Meyer G

    更新日期:2012-12-01 00:00:00

  • Intracellular signaling triggered by antiphospholipid antibodies in platelets and endothelial cells: a pathway to targeted therapies.

    abstract::Understanding the intracellular events triggered by antiphospholipid (aPL) antibodies in platelets and endothelial cells (ECs) is important in designing new modalities of targeted therapies for the treatment of thrombosis in Antiphospholipid Syndrome (APS). A recent study showed a significant increase in the expressio...

    journal_title:Thrombosis research

    pub_type: 杂志文章,评审

    doi:10.1016/j.thromres.2004.06.031

    authors: Pierangeli SS,Vega-Ostertag M,Harris EN

    更新日期:2004-01-01 00:00:00

  • Reduction of factor FVIIa activity during heparin therapy. Evidence for assay interactions with tissue factor pathway inhibitor and antithrombin.

    abstract::Heparin is known to exert its antithrombotic effects by accelerating the effect of antithrombin (AT) and by mobilizing tissue factor pathway inhibitor (TFPI) into the circulation from vascular endothelium. Heparin treatment has been reported to decrease FVIIa activity by 40%; this was suggested as a new antithrombotic...

    journal_title:Thrombosis research

    pub_type: 杂志文章

    doi:10.1016/s0049-3848(00)00343-1

    authors: Hansen JB,Svensson B,Sandset PM,Thijssen F

    更新日期:2000-12-01 00:00:00

  • Venous thromboembolism after fast-track unicompartmental knee arthroplasty - A prospective multicentre cohort study of 3927 procedures.

    abstract:INTRODUCTION:Unicompartmental knee arthroplasty (UKA) has increased due to potential favourable complication rates when compared to total knee arthroplasty (TKA). Although venous thromboembolism (VTE) is a well-documented complication after TKA limited data is available after UKA and mostly presented as secondary findi...

    journal_title:Thrombosis research

    pub_type: 杂志文章

    doi:10.1016/j.thromres.2020.07.002

    authors: Petersen PB,Jørgensen CC,Gromov K,Kehlet H,Lundbeck Foundation Centre for Fast-track Hip and Knee Replacement Collaborative Group.

    更新日期:2020-11-01 00:00:00

  • Frequency of use and acceptability of clinical prediction rules for pulmonary embolism among Swiss general internal medicine residents.

    abstract:INTRODUCTION:Whether clinical prediction rules for pulmonary embolism are accepted and used among general internal medicine residents remains uncertain. We therefore evaluated the frequency of use and acceptability of the Revised Geneva Score (RGS) and the Pulmonary Embolism Severity Index (PESI), and explored which fa...

    journal_title:Thrombosis research

    pub_type: 杂志文章

    doi:10.1016/j.thromres.2017.09.028

    authors: Faller N,Stalder O,Limacher A,Bassetti S,Beer JH,Genné D,Battegay E,Hayoz D,Leuppi J,Mueller B,Perrier A,Waeber G,Rodondi N,Aujesky D

    更新日期:2017-12-01 00:00:00

  • Comparison of antithrombin activity of the polysulphate chitosan derivatives in in vivo and in vitro system.

    abstract::In order to choose the proper method for evaluating the antithrombin activity in samples of chitosan polysulphate (CP) with different polymerization degrees and sulphation degrees, we estimated the ability of direct anticoagulants to depress the coagulability of recalcified sheep blood using the third international he...

    journal_title:Thrombosis research

    pub_type: 杂志文章

    doi:10.1016/s0049-3848(01)00266-3

    authors: Drozd NN,Sher AI,Makarov VA,Galbraikh LS,Vikhoreva GA,Gorbachiova IN

    更新日期:2001-06-01 00:00:00

  • C-terminal peptide alcohol, acid and amide analogs of desulfato hirudin54-65 as antithrombin agents.

    abstract::Analogs of the antithrombin peptide hirudin54-65 with C-terminal modifications have been synthesized in order to examine the requirements for alpha-thrombin inhibition. The C-terminal residue, Gln65, could be replaced with L-amino acids or amino alcohols with neutral or charged hydrophilic side chains without greatly ...

    journal_title:Thrombosis research

    pub_type: 杂志文章

    doi:10.1016/0049-3848(89)90090-x

    authors: Krstenansky JL,Payne MH,Owen TJ,Yates MT,Mao SJ

    更新日期:1989-05-15 00:00:00

  • The role of the red cell membrane in thrombin generation.

    abstract::Red blood cells have historically been viewed as innocent bystanders in the process of blood coagulation and thrombin generation; however a century of clinical evidence linking red blood cells to thrombosis suggests the contrary. In this brief review, the biochemical evidence for red blood cell involvement in thrombin...

    journal_title:Thrombosis research

    pub_type: 杂志文章,评审

    doi:10.1016/j.thromres.2013.01.023

    authors: Whelihan MF,Mann KG

    更新日期:2013-05-01 00:00:00

  • The spectrum of thrombin in acute coronary syndromes.

    abstract::The role of thrombin in vascular physiology and pathophysiology continues to impact our understanding of many cellular processes and systems including the function of platelets, endothelial cells, smooth muscle cells, leukocytes and the regulation of the coagulation cascade. Recent acute coronary syndrome clinical tri...

    journal_title:Thrombosis research

    pub_type: 杂志文章,评审

    doi:10.1016/j.thromres.2015.02.013

    authors: Giri S,Jennings LK

    更新日期:2015-05-01 00:00:00

  • Pharmacokinetics of Defibrotide and of its profibrinolytic activity in the rabbit.

    abstract::An extensive study of the pharmacokinetics and the pharmacokinetics of the profibrinolytic activity of Defibrotide (D) in the rabbit has been made. a two compartment model was used to describe D's pharmacokinetics. The parameters of drug disposition and the rate constant of release from tissues to central compartment ...

    journal_title:Thrombosis research

    pub_type: 杂志文章

    doi:10.1016/0049-3848(83)90391-2

    authors: Pescador R,Mantovani M,Prino G,Madonna M

    更新日期:1983-04-01 00:00:00

  • Impact of VKORC1 gene polymorphism on interindividual and interethnic warfarin dosage requirement--a systematic review and meta analysis.

    abstract:INTRODUCTION:Warfarin is the most widely used oral anticoagulant. It has been suggested that anticoagulation effect of warfarin is significantly associated with the polymorphism of certain genes, including Cytochrome P450 complex subunit 2C9 (CYP2C9), Vitamin K Epoxide Reductase Complex Subunit 1 (VKORC1), Gamma-Glutam...

    journal_title:Thrombosis research

    pub_type: 杂志文章,meta分析,评审

    doi:10.1016/j.thromres.2009.10.017

    authors: Yang L,Ge W,Yu F,Zhu H

    更新日期:2010-04-01 00:00:00

  • Postpartum blood transfusion and hemorrhage as independent risk factors for venous thromboembolism.

    abstract:INTRODUCTION:Profuse postpartum hemorrhage (PPH) and red blood cell (RBC) transfusion have been suggested to be associated with venous thromboembolic events (VTE). However, it is not fully clear if they are independent major risk factors. METHODS:Women who gave birth in the Stockholm area between 1999 and 2002 were th...

    journal_title:Thrombosis research

    pub_type: 杂志文章

    doi:10.1016/j.thromres.2018.03.002

    authors: Thurn L,Wikman A,Lindqvist PG

    更新日期:2018-05-01 00:00:00

  • Plasma viscosity and related cardiovascular risk factors in a Spanish Mediterranean population.

    abstract:INTRODUCTION:Plasma viscosity (PV) constitutes an independent important predictor of initial and recurrent cardiac events and mortality. It has been suggested that there is a geographical variation in PV values related to coronary event rates. Little information exists regarding PV in Spain. Therefore, our objective wa...

    journal_title:Thrombosis research

    pub_type: 杂志文章

    doi:10.1016/j.thromres.2006.11.009

    authors: Vayá A,Simó M,Santaolaria M,Carrasco P,Corella D

    更新日期:2007-01-01 00:00:00

  • Antiphospholipid antibodies in children without and in adults with and without thrombophilia.

    abstract::Antiphospholipid antibodies (APAs) are considered risk factors in patients with thromboembolic diseases. Although the incidence of such acquired coagulation disturbances in adults are well described, only few data exist for children. Therefore, in a first step to collect new data we analyzed the presence of different ...

    journal_title:Thrombosis research

    pub_type: 杂志文章

    doi:10.1016/s0049-3848(99)00241-8

    authors: Siemens HJ,Gutsche S,Brückner S,Bucsky P,Katus HA

    更新日期:2000-05-15 00:00:00

  • Platelet membrane glycoprotein V: characterization of the thrombin-sensitive glycoprotein from human platelets.

    abstract::Human platelets contain a single membrane glycoprotein which is susceptible to thrombin proteolysis, glycoprotein V. We have purified 1 mg of glycoprotein V from 10(13) platelets using a combination of gel filtration, hydroxylapatite and ion-exchange chromatographies. Glycoprotein V has a blocked amino-terminus. Follo...

    journal_title:Thrombosis research

    pub_type: 杂志文章

    doi:10.1016/0049-3848(89)90113-8

    authors: Zafar RS,Walz DA

    更新日期:1989-01-01 00:00:00

  • Disulfide bond exchanges in integrins αIIbβ3 and αvβ3 are required for activation and post-ligation signaling during clot retraction.

    abstract:BACKGROUND:Integrin αIIbβ3 mediates platelet adhesion, aggregation and fibrin clot retraction. These processes require activation of αIIbβ3 and post-ligation signaling. Disulfide bond exchanges are involved in αIIbβ3 and αvβ3 activation. METHODS:In order to investigate the role of integrin activation and disulfide bon...

    journal_title:Thrombosis research

    pub_type: 杂志文章

    doi:10.1016/j.thromres.2014.02.001

    authors: Mor-Cohen R,Rosenberg N,Averbukh Y,Seligsohn U,Lahav J

    更新日期:2014-05-01 00:00:00

  • Thromboprophylaxis with low molecular weight heparin (dalteparin) in pregnancy.

    abstract::Venous thromboembolism remains an important cause of maternal mortality. For women at risk during pregnancy, the recommended venous thromboembolismprophylaxis is unfractionated heparin. Low molecular weight heparins, such as dalteparin, also may be suitable, but randomised trials have not been performed. Pregnant wome...

    journal_title:Thrombosis research

    pub_type: 临床试验,杂志文章,多中心研究,随机对照试验

    doi:10.1016/s0049-3848(99)00110-3

    authors: Pettilä V,Kaaja R,Leinonen P,Ekblad U,Kataja M,Ikkala E

    更新日期:1999-11-15 00:00:00

  • Impaired flow mediated dilatation as evidence of endothelial dysfunction in chronic atrial fibrillation: relationship to plasma von Willebrand factor and soluble E-selectin levels.

    abstract:BACKGROUND:Impaired endothelial-dependent flow-mediated dilatation (FMD) has been used to demonstrate endothelial dysfunction in a wide variety of cardiovascular disease, but previous studies have excluded patients with atrial fibrillation(AF). We therefore hypothesised that endothelial dysfunction exists in AF and tha...

    journal_title:Thrombosis research

    pub_type: 杂志文章

    doi:10.1016/j.thromres.2007.09.008

    authors: Freestone B,Chong AY,Nuttall S,Lip GY

    更新日期:2008-01-01 00:00:00

  • Plasma endothelin-1 level as a predictor for poor collaterals in patients with ≥95% coronary chronic occlusion.

    abstract:BACKGROUND:Coronary collateral circulation (CCC) plays an important role in protecting myocardium from ischemic damage. The studies on factors which impact on CCC might be of great clinical interest. The aim of the present study was to evaluate endothelin-1 (ET-1) as a potential predictor for poor or good CCC in patien...

    journal_title:Thrombosis research

    pub_type: 杂志文章

    doi:10.1016/j.thromres.2016.04.007

    authors: Fan Y,Li S,Li XL,Lin XL,Zhu CG,Xu RX,Qing P,Wu NQ,Jiang LX,Xu B,Gao RL,Li JJ

    更新日期:2016-06-01 00:00:00

  • The interaction of platelet proteins with three fibroblast-derived collagenases.

    abstract::Three collagenases were purified from the culture medium of human skin fibroblasts using ammonium sulfate fractionation, ion-exchange chromatography and gel filtration. The cationic collagenase had a molecular weight of 42,000; two anionic collagenases had molecular weights of 63,000 and 115,000. Preincubation of the ...

    journal_title:Thrombosis research

    pub_type: 杂志文章

    doi:10.1016/0049-3848(84)90211-1

    authors: Pisoni R,Ciaglowski RE,Brown RK,Walz DA

    更新日期:1984-07-15 00:00:00

  • Plasma and platelet skimming at T-junctions.

    abstract::Separation of plasma, erythrocytes, and platelets was studied in T-shaped bifurcations prepared by a casting technique. The diameters of the side and main channel were 100 microns and 200 microns, respectively. Small blood samples (about 20 microliters) were collected from the side channel for determination of erythro...

    journal_title:Thrombosis research

    pub_type: 杂志文章

    doi:10.1016/0049-3848(87)90314-8

    authors: Perkkiö J,Wurzinger LJ,Schmid-Schönbein H

    更新日期:1987-03-01 00:00:00

  • A sensitive competitive binding assay for exogenous and endogenous heparins.

    abstract::A new type of assay for heparins has been devised, in which the test material competes with 125I-labelled heparin for binding to protamine-Sepharose. The assay is very sensitive and will measure heparin concentrations down to 10 ng ml-1. It responds to both the degree of sulphation and the molecular weight of acidic p...

    journal_title:Thrombosis research

    pub_type: 杂志文章

    doi:10.1016/0049-3848(82)90056-1

    authors: Dawes J,Pepper DS

    更新日期:1982-08-15 00:00:00

  • Protein C activity levels in endotoxin-induced disseminated intravascular coagulation in a dog model.

    abstract::The levels of protein C (PC) and other coagulation factors were monitored during endotoxin-induced disseminated intravascular coagulation (DIC) in the dog. Initial evaluation of the effectiveness of intradermal administration of bolus endotoxin quantities into the dog, demonstrated induction of DIC in the canine, with...

    journal_title:Thrombosis research

    pub_type: 杂志文章

    doi:10.1016/0049-3848(89)90062-5

    authors: Madden RM,Ward M,Marlar RA

    更新日期:1989-08-01 00:00:00

  • Residual perfusion defects in patients with pulmonary embolism are related to impaired fibrinolytic capacity.

    abstract:BACKGROUND:Few studies investigated the relationship between fibrinolysis abnormalities and residual pulmonary perfusion defects after acute pulmonary embolism (PE). OBJECTIVE:To assess the fibrinolytic profile in patients with prior PE in relation to the extent of scintigraphically detectable residual perfusion abnor...

    journal_title:Thrombosis research

    pub_type: 杂志文章

    doi:10.1016/j.thromres.2014.07.013

    authors: Lami D,Cellai AP,Antonucci E,Fiorillo C,Becatti M,Grifoni E,Cenci C,Marcucci R,Mannini L,Miniati M,Abbate R,Prisco D

    更新日期:2014-09-01 00:00:00

  • Beyond cell based models of coagulation: analyses of coagulation with clot "lifespan" resistance-time relationships.

    abstract::Cell based models of coagulation (CBM) have provided mechanistic insight into numerous hematological issues for nearly two decades. This review discusses another coagulation model system--the clot lifespan model (CLSM)--that has been designed to compliment the CBM-based approach to elucidating the mechanisms responsib...

    journal_title:Thrombosis research

    pub_type: 杂志文章,评审

    doi:10.1016/j.thromres.2007.09.003

    authors: Nielsen VG

    更新日期:2008-01-01 00:00:00

  • Changes in the fibrinolytic system in patients with peripheral arterial occlusive disease undergoing percutaneous transluminal angioplasty.

    abstract::We have investigated fibrinolytic parameters in 33 patients with peripheral arterial occlusive disease (PAOD) before and 6, 24, and 48 hours after percutaneous transluminal angioplasty (PTA) as well as in 35 gender-matched healthy controls, whose mean age was not significantly different from the mean age of the patien...

    journal_title:Thrombosis research

    pub_type: 杂志文章

    doi:10.1016/s0049-3848(99)00002-x

    authors: Roller RE,Janisch S,Carroll V,Kvas E,Pilger E,Binder BR,Wojta J

    更新日期:1999-05-15 00:00:00

  • Helenalin and 11 alpha,13-dihydrohelenalin, two constituents from Arnica montana L., inhibit human platelet function via thiol-dependent pathways.

    abstract::This study investigates the effect on human platelet function of two sesquiterpene lactones from Arnica montana L., helenalin (H) and 11 alpha,13-dihydrohelenalin (DH). Both compounds inhibited collagen-induced platelet aggregation, thromboxane formation and 5-hydroxytryptamine secretion in a concentration-dependent m...

    journal_title:Thrombosis research

    pub_type: 杂志文章

    doi:10.1016/0049-3848(90)90151-2

    authors: Schröder H,Lösche W,Strobach H,Leven W,Willuhn G,Till U,Schrör K

    更新日期:1990-03-15 00:00:00

  • Impaired platelet binding of fibrinogen due to a lower number of GPIIB/IIIA receptors in polycythemia vera.

    abstract::We have previously described a stimulus-specific defect in platelet aggregation in polycythaemia vera (PV) after stimulation with surface receptor dependent agonists such as platelet activating factor (PAF). In contrast, responses to phorbol myristate acetate (PMA) were normal. We now report that after PAF stimulation...

    journal_title:Thrombosis research

    pub_type: 杂志文章

    doi:10.1016/s0049-3848(98)00096-6

    authors: Le Blanc K,Lindahl T,Rosendahl K,Samuelsson J

    更新日期:1998-09-15 00:00:00

  • The effect of myelin basic protein on the endogenous phosphorylation of platelets.

    abstract::Bovine myelin basic protein (BP) induced a shape change and endogenous phosphorylation of a 45,000 (45K) molecular weight protein of intact human platelets. This effect occurred rapidly over an effective concentration range of 5-100 microM BP. BP peptides encompassing residues 1-42, 43-88, and 89-169 from the BP molec...

    journal_title:Thrombosis research

    pub_type: 杂志文章

    doi:10.1016/0049-3848(82)90090-1

    authors: Chiang TM,Whitaker JN,Kang AH,Beachey EH

    更新日期:1982-03-15 00:00:00