Abstract:
:Major orthopaedic surgery is associated with an increased risk of venous thromboembolism. Direct oral anticoagulants (DOACs) are recommended as thromboprophylactic agents after orthopaedic surgery. Although routine monitoring of DOACs in general is not required, measuring DOAC concentration may be necessary in clinical settings. The effects of DOACs on routine coagulation assays in spiked material are studied extensively, however, few data are available on DOAC concentration in patients after major orthopaedic surgery. We measured trough and peak DOAC concentrations with UPLC-MS/MS and routine coagulation tests in a prospective study including 40 patients receiving thromboprophylactic treatment with dabigatran 220mg od and 40 patients receiving rivaroxaban 10mg od after major orthopaedic surgery. For rivaroxaban, the median trough concentration with UPLC-MS/MS was 17.1ng/mL and median peak concentration was 149ng/mL. The anti-Xa assay displayed a good correlation, but a positive bias in comparison to the reference method. Furthermore, trough levels were mostly below the LOD of the anti-Xa assay. For dabigatran, the median trough concentration with UPLC-MS/MS was 12.1ng/mL, and median peak level was 80.8ng/mL. A positive bias was found when results from coagulation assays were compared to UPLC-MS/MS data. However, the addition of glucuronidated metabolites to dabigatran concentration UPLC-MS/MS data generally resolved most of this bias. Age was found to have a significant influence on dabigatran pharmacokinetics, irrespective of kidney function, whereas no effect of age was found during rivaroxaban treatment. In both treatment groups, female subjects displayed faster pharmacokinetics in comparison to male subjects, although not reaching significance. We conclude that UPLC-MS/MS is the method of choice to measure trough concentrations of DOACs in patients after orthopaedic surgery. Current coagulation assays are not suited for this purpose. We found large heterogeneity in both peak and trough concentrations of DOACs, and showed that pharmacokinetics of novel oral anticoagulants may be influenced by age and gender. Whether patients with high or low trough concentrations are at increased risk for bleeding or thromboembolic events respectively remains to be established.
journal_name
Thromb Resjournal_title
Thrombosis researchauthors
Schellings MW,Boonen K,Schmitz EM,Jonkers F,van den Heuvel DJ,Besselaar A,Hendriks JG,van de Kerkhof Ddoi
10.1016/j.thromres.2016.01.012subject
Has Abstractpub_date
2016-03-01 00:00:00pages
128-34eissn
0049-3848issn
1879-2472pii
S0049-3848(16)30015-9journal_volume
139pub_type
临床试验,杂志文章abstract::The complex relation between thrombotic thrombocytopenic purpura (TTP) and pregnancy is concisely reviewed. Pregnancy is a very strong trigger for acute disease manifestation in patients with hereditary TTP caused by double heterozygous or homozygous mutations of ADAMTS13 (ADisintegrin And Metalloprotease with Thrombo...
journal_title:Thrombosis research
pub_type: 杂志文章,评审
doi:10.1016/S0049-3848(15)50437-4
更新日期:2015-02-01 00:00:00
abstract::The fibrinogen molecule consists of two sets of Aalpha, Bbeta, and gamma chains assembled into a bilateral disulfide linked (Aalpha, Bbeta, gamma)2 structure. Cleavage of the two A-fibrinopeptides (FPA, Aalpha1-16) from normal Aalpha chains with arginine at position 16 (RFPA) by thrombin or the venom enzyme atroxin tr...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/s0049-3848(00)00383-2
更新日期:2001-01-15 00:00:00
abstract::A synthetic pentasaccharide, representing the critical sequence required in heparin for binding to antithrombin III (AT III), produces strong anti-factor Xa activity in vitro in the presence of AT III and is devoid of any activity directed towards thrombin. This pentasaccharide provides a unique tool to study the ques...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(87)90280-5
更新日期:1987-04-15 00:00:00
abstract::In this study we examined in 100 patients testing positive for Helicobacter pylori infection whether successful eradication therapy with pantoprazole, clarithromycin, and metronidazole alters fibrinogen and other acute phase response markers. Of 100 patients, only 11 showed a fibrinogen level above 300 mg/dL. Successf...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/s0049-3848(99)00230-3
更新日期:2000-03-15 00:00:00
abstract::Anticoagulant properties of three sulfated compounds prepared from xylans isolated from corn cobs, larchwood and oatspelts were compared with heparin and sodium pentosan polysulfate (SP-54) by studying their effects on activated partial thromboplastin time (APTT), prothrombin time (PT) and thrombin time (TT) using poo...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(87)90148-4
更新日期:1987-08-01 00:00:00
abstract:INTRODUCTION:In-vitro and in-vivo models suggest the influence of low-molecular weight heparin on conception in infertile women undergoing in vitro fertilization procedures (IVF). In this randomized controlled trial we assessed whether a low-molecular weight heparin (parnaparin) could affect IVF outcomes. MATERIALS AN...
journal_title:Thrombosis research
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.thromres.2017.08.006
更新日期:2017-11-01 00:00:00
abstract::It has become customary to regard the various glycerophospholipids as quite similar, and the acyl groups are considered to have little influence on the behaviour of the lipids in membranes or metabolism. Nevertheless, a number of recent observations by the authors and others indicate a high degree of metabolic compart...
journal_title:Thrombosis research
pub_type: 杂志文章,评审
doi:10.1016/0049-3848(92)90006-v
更新日期:1992-08-01 00:00:00
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
更新日期:2008-01-01 00:00:00
abstract::The antithrombotic actions of selective factor Xa (FXa) inhibitors, recombinant tick anticoagulant peptide (rTAP) and DX-9065a, were evaluated in experimental thrombosis models in anesthetized rats. In the first model, thrombosis was induced by exposing flowing blood to a silk thread anchored in an arteriovenous (AV) ...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(96)00112-0
更新日期:1996-07-15 00:00:00
abstract::The time course and degree of collagen induced platelet shape change, aggregation and ATP-secretion in citrated human platelet rich plasma was monitored with a lumi-aggregometer. Onset of ATP-secretion was measurable within seconds after collagen challenge and always distinctly before onset of shape change. In absence...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(86)90089-7
更新日期:1986-08-15 00:00:00
abstract::Thrombus formation was electrically induced in the left common carotid artery of rats with preoccluded both vertebral and right carotid arteries. Following thrombus induction, animals became unresponsive and lost their righting reflex. The loss of righting reflex was observed when cortical tissular pO2 reached 55 +/- ...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(87)90340-9
更新日期:1987-10-01 00:00:00
abstract::In this paper, we demonstrated that the procoagulant action of Lonomia achelous (Cramer) is due in part to a component that activates prothrombin. The activation by crude venom and Fractions obtained by gel filtration on Sephadex G-75 is not dependent of phospholipid, Ca++ or Factor V. The activation of prothrombin by...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(92)90187-f
更新日期:1992-05-01 00:00:00
abstract:INTRODUCTION:After major liver surgery, there are risks of both postoperative bleeding and thrombosis. Routine coagulation monitoring is indicated, but may not provide adequate clinical guidance. Thus, we described the clotting status in a pilot study using broader coagulation testing. We analysed the temporal pattern ...
journal_title:Thrombosis research
pub_type: 临床试验,杂志文章
doi:10.1016/j.thromres.2015.05.023
更新日期:2015-08-01 00:00:00
abstract:INTRODUCTION:Antithrombin (AT), protein C (PC) and protein S (PS) deficiencies are risk factors for venous thromboembolism. Overlapping values between heterozygous carriers and normal individuals often make a correct classification of a deficiency difficult. The aim of this study was to investigate the effect of sex, a...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2013.07.003
更新日期:2013-08-01 00:00:00
abstract:BACKGROUND:Early aspirin treatment is widely used to inhibit platelet activity and to reduce morbidity and mortality in patients presenting with an acute myocardial infarction or a stroke. A number of different aspirin formulations have been used for this purpose; however, a comparison of their effectiveness in inhibit...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2005.10.001
更新日期:2006-01-01 00:00:00
abstract::Three commercial thrombin preparations used clinically to stop topical bleeding were studied. The specific activities of these preparations were 1,064 U/mg (human); 59 U/mg (bovine) and 147 U/mg (bovine). SDS-PAGE analysis of the human product produced one major band corresponding to a molecular weight of alpha-thromb...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(89)90102-3
更新日期:1989-02-01 00:00:00
abstract::Thrombocytopenia is a common finding in cancer patients and can have different and/or multifactorial pathogenesis. While in solid tumors it occurs often as a consequence of chemotherapy treatment, it is frequently observed at diagnosis in patients with hematological malignancies being aggravated to a potentially life-...
journal_title:Thrombosis research
pub_type: 杂志文章,评审
doi:10.1016/j.thromres.2018.02.001
更新日期:2018-04-01 00:00:00
abstract::HC II functional assays are generally preferred with respect to immunochemical assays. Nevertheless functional assays can be biased by the antithrombin III (AT III)-heparin complex activity; in fact trace amounts of heparin generally contaminate dermatan sulfate (DS) commercial preparations used as HC II reaction acti...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(92)90248-9
更新日期:1992-01-15 00:00:00
abstract:INTRODUCTION:Conventional Vacutainer® Sodium Citrate blood collection tubes contain a relatively high concentration of contaminating magnesium ions, which may result in shortening of the prothrombin time (PT) and the International Normalized Ratio (INR). Recently the manufacturer of Vacutainer® Sodium Citrate tubes int...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2014.04.016
更新日期:2014-07-01 00:00:00
abstract:INTRODUCTION:The A-subunit of blood coagulation factor XIII is a pro-transglutaminase, which cross-links α- and γ-fibrin-chains in its activated form. Selective inhibitors against FXIII-A may be desirable drugs to prevent the development of thromboses. Animal models are generally used for proof of principle and for tox...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2013.02.008
更新日期:2013-05-01 00:00:00
abstract:INTRODUCTION:Elevated soluble urokinase-type plasminogen activator receptor (suPAR) indicates an inflammatory state caused by conditions such as HIV and cancer. Recently suPAR was identified as an indicator of cardiovascular disease (CVD). CVD is highly prevalent in black South Africans, but the potential role of suPAR...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2011.10.034
更新日期:2012-08-01 00:00:00
abstract::Patients who had survived a stroke or transient ischaemic attacks (TIA) were admitted to a trial of low-dose aspirin (50 mg) alone, sustained release dipyridamole (400 mg/day) alone, or a combination of the two agents, and results compared with a placebo over 24 months. This low-dose aspirin regimen produced in pairwi...
journal_title:Thrombosis research
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1016/s0049-3848(98)00099-1
更新日期:1998-09-15 00:00:00
abstract:BACKGROUND:Abdominal obesity has been found to be associated with an increased risk of deep vein thrombosis (DVT). Whether patients with abdominal obesity have an increased risk of recurrence is currently unknown. METHODS:Patients with objective diagnosis of DVT and a life expectancy of greater than 6 months underwent...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2006.05.013
更新日期:2007-01-01 00:00:00
abstract::The placenta is the highly specialised organ of pregnancy that supports the normal growth and development of the fetus. Growth and function of the placenta are precisely regulated and coordinated to ensure the exchange of nutrients and waste products between the maternal and fetal circulatory systems operates at maxim...
journal_title:Thrombosis research
pub_type: 杂志文章,评审
doi:10.1016/j.thromres.2004.06.038
更新日期:2004-01-01 00:00:00
abstract::Practice variation, the differences in clinical management between physicians, is one reason why patient outcomes may differ. Identifying factors that contribute to practice variation in areas of clinical uncertainty or equipoise may have implications for understanding and improving patient care. To discern what facto...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2017.09.026
更新日期:2017-11-01 00:00:00
abstract::Atherothrombosis is the leading cause of morbidity and mortality in patients with diabetes mellitus. Several mechanisms contribute to the diabetic prothrombotic state, including endothelial dysfunction, coagulative activation and platelet hyper-reactivity. In particular, diabetic platelets are characterised by dysregu...
journal_title:Thrombosis research
pub_type: 杂志文章,评审
doi:10.1016/j.thromres.2011.11.052
更新日期:2012-03-01 00:00:00
abstract:INTRODUCTION:D-dimer, a fibrin degradation product, is related to risk of cardiovascular disease and venous thromboembolism. Genetic determinants of D-dimer are not well characterized; notably, few data have been reported for African American (AA), Asian, and Hispanic populations. MATERIALS AND METHODS:We conducted a ...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2014.05.018
更新日期:2014-08-01 00:00:00
abstract:BACKGROUND:Clinical parameters, biomarkers and imaging-based risk stratification are widely accepted in pulmonary embolism(PE). The present study has investigated the prognostic role of simplified Pulmonary Embolism Severity Index (sPESI) score and the European Society of Cardiology (ESC) model. METHODS:This prospecti...
journal_title:Thrombosis research
pub_type: 杂志文章,多中心研究
doi:10.1016/j.thromres.2014.02.032
更新日期:2014-06-01 00:00:00
abstract:BACKGROUND:The aim of this study was to describe platelet aggregation characteristics by multiple electrode aggregometry (MEA) and to evaluate MEA for its potential to detect platelet dysfunction and response to anti-aggregatory drugs in patients with myeloproliferative disorders (MPD). METHODS:We compared the platele...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2010.06.014
更新日期:2010-09-01 00:00:00
abstract::Defibrotide both "in vitro" and "ex vivo" decreases PMN adhesion to nylon columns. This activity is blunted by 8-phenyltheophylline, a known blocker of adenosine A1/A2 receptors, suggesting that Defibrotide acts on that kind of receptors. Indomethacin, a blocker of PGI2 synthesis, did not cancel DFT's activity, sugges...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(95)00178-t
更新日期:1995-11-15 00:00:00