Abstract:
INTRODUCTION:Many antithrombotic drugs may have a deleterious effect on normal haemostasis leading to bleeding complications. The aim of this study was to determine if sub-therapeutic (low) doses of antithrombotic agents, when administered in combination, have enhanced efficacy without augmentation of bleeding time. MATERIALS AND METHODS:The antithrombotic effects of i.v. aspirin (4-30 mg/kg), heparin (100-500 U/kg), enoxaparin (4-30 mg/kg) and clopidogrel (10-20 mg/kg) were studied in a rat Folts-like preparation of carotid arterial thrombosis. The frequency of cyclic flow reductions (CFRs; indicating occlusive thrombus formation) and bleeding time were measured. Drug doses that were singly ineffective at preventing occlusive thrombus formation were tested in the following combinations: aspirin (10 mg/kg) with heparin (250 U/kg); aspirin (4 mg/kg) with enoxaparin (4 mg/kg); and aspirin (10 mg/kg) with clopidogrel (10 mg/kg). RESULTS:Control period (pretreatment) CFRs were not significantly different between groups; average 7.0+/-0.3 CFRs/30 min (n=64). Tail bleeding time before drug(s) was 3.1+/-0.1 min (n=86). When administered alone, aspirin (4-30 mg/kg), heparin (250 U/kg) or enoxaparin (4 mg/kg) had no effect on CFRs or bleeding time. Heparin (500 U/kg), enoxaparin (10 and 30 mg/kg) and clopidogrel (20 mg/kg) significantly decreased CFRs. Single administration of heparin (500 U/kg) or enoxaparin (30 mg/kg) increased bleeding time by 4- or 11-fold. When co-administered, aspirin 10 mg/kg and heparin 250 U/kg decreased CFRs, but also increased bleeding time by 11-fold. However, combination of aspirin and enoxaparin (4 mg/kg each), or aspirin and clopidogrel (10 mg/kg each), decreased CFRs with no effect on bleeding. CONCLUSIONS:In a preparation of arterial thrombosis in the rat, combinations of sub-efficacious (low) doses of aspirin with enoxaparin or clopidogrel inhibited thrombus formation without augmenting bleeding time. However, low-dose aspirin combined with heparin, whilst inhibiting thrombus formation, exacerbated bleeding time. If these findings translate into the clinic, the use of effective low-dose combinations may have therapeutic advantages.
journal_name
Thromb Resjournal_title
Thrombosis researchauthors
Daykin HJ,Sturgeon SA,Jones C,Wright CEdoi
10.1016/j.thromres.2005.11.015subject
Has Abstractpub_date
2006-01-01 00:00:00pages
755-62issue
6eissn
0049-3848issn
1879-2472pii
S0049-3848(05)00452-4journal_volume
118pub_type
杂志文章abstract::The effect of warfarin-induced factor VII deficiency on the skin bleeding time was investigated in 10 consecutive patients with mean prothrombin times of 33 sec and factor VII levels of 7%. Bleeding times in all but one subject were entirely within the normal range. We conclude that warfarin administration, even to th...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(83)90243-8
更新日期:1983-02-15 00:00:00
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
更新日期:2000-05-15 00:00:00
abstract:INTRODUCTION:Hemolytic uremic syndrome is a thrombotic microangiopathy. Clopidogrel, a recently developed platelet aggregation inhibitor, has not been previously reported as a treatment for this illness. Our study's objective was to explore the efficacy and safety of clopidogrel in children with diarrhea associated hem...
journal_title:Thrombosis research
pub_type: 临床试验,杂志文章
doi:10.1016/j.thromres.2012.05.017
更新日期:2012-09-01 00:00:00
abstract::Acute coronary syndromes (ACS) represent the main clinical manifestation of atherosclerotic progression in the coronary district. Thrombosis plays a critical role in the patho-anatomical of ACS, as disruption of an atherosclerotic plaque exposes flowing blood to subendothelial collagen, tissue factor, and other procoa...
journal_title:Thrombosis research
pub_type: 杂志文章,评审
doi:10.1016/j.thromres.2011.12.026
更新日期:2012-03-01 00:00:00
abstract:BACKGROUND:Tissue factor pathway inhibitor-2 (TFPI-2) regulates matrix metalloproteinases activation and extracellular matrix degradation. Over-expression of TFPI-2 enhances atherosclerotic plaque stability. The aim of this study is to investigate the effect of conditional knockout (KO) of TFPI-2 in vascular endothelia...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2015.11.010
更新日期:2016-01-01 00:00:00
abstract::A frequent complication of venous access devices (VADs) is axillary-subclavian venous thrombosis. To study this problem we have compared blood drawn through VADs with peripheral blood samples in a group of oncology patients with venographically demonstrated venous damage (N = 14) and a group with normal venograms (N =...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(95)00125-b
更新日期:1995-08-15 00:00:00
abstract:INTRODUCTION:We recently proposed a scale for assessment of patient-relevant functional limitations following an episode of venous thromboembolism (VTE). Further development of this post-VTE functional status (PVFS) scale is still needed. METHODS:Guided by the input of VTE experts and patients, we refined the PVFS sca...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2020.03.020
更新日期:2020-06-01 00:00:00
abstract::Studies of the factors affecting the first recurrence of ischemic stroke have reported inconsistent findings. Types of initial stroke and the racial differences in study samples are among the explanations that may account for this inconsistency. The aims of this study were to estimate the cumulative recurrence rates o...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/s0049-3848(99)00146-2
更新日期:2000-02-01 00:00:00
abstract::The effects of hydrogen peroxide on factor Xa-catalyzed prothrombin activation on the surface of vascular endothelial cells, and the inhibitory effect of sphingosine on prothrombin activation were studied in cultured calf pulmonary artery endothelial cells (CPAEC). Hydrogen peroxide enhanced factor Xa-catalyzed prothr...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(92)90263-a
更新日期:1992-07-01 00:00:00
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
更新日期:2010-04-01 00:00:00
abstract::The changes in the fibrinolytic system of rats induced by repeated injections of tissue plasminogen activator (TPA) have been studied. The euglobulin fraction fibrinolytic activity increases 10 min after the first injection of TPA. Repeated injections of TPA for one or more days do not stimulate the fibrinolytic activ...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(82)90075-5
更新日期:1982-08-01 00:00:00
abstract:INTRODUCTION:Previous studies have suggested the used of off-label recombinant factor VII (rFVIIa) increases the risk of thromboembolic events, but the effect of the dose of rFVIIa is not well described in the literature. MATERIALS AND METHODS:All adult patients that received off-label rFVIIa from 2005-2012 were inclu...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2014.02.026
更新日期:2014-05-01 00:00:00
abstract::Generally, the rules of good practice in transfusion medicine apply also to the pediatric age group. However, the frequency of specific diseases that might necessitate the administration of fresh frozen plasma (FFP) differs from that in adults. Physiologic differences to the later age exist in the neonatal period and ...
journal_title:Thrombosis research
pub_type: 杂志文章,评审
doi:10.1016/s0049-3848(02)00149-4
更新日期:2002-10-31 00:00:00
abstract::The present investigation has used an aggregation-disaggregation-reaggregation model to determine if exposure to potent aggregating agents causing a refractory state in deaggregated platelets results in down-regulation and clearance of GPIb/IX, the receptor for von willebrand factor. Thrombin, the thrombin receptor ac...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/s0049-3848(96)00185-5
更新日期:1996-11-15 00:00:00
abstract::Prothrombin time is a standard screening test to monitor patients treated with oral anticoagulants. We hypothesize that INR measurements will not vary a lot within a given day in a given patient. The present study was thus conducted to compare the change of the international normalized ratio (INR) of prothrombin time ...
journal_title:Thrombosis research
pub_type: 临床试验,杂志文章
doi:10.1016/s0049-3848(02)00339-0
更新日期:2002-09-01 00:00:00
abstract:INTRODUCTION:The activated partial thromboplastin time (APTT) is commonly used to monitor unfractionated heparin (UFH) but may not accurately measure the amount of heparin present. The anti-Xa assay is less susceptible to confounding factors and may be a better assay for this purpose. MATERIALS AND METHODS:The validit...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2017.07.006
更新日期:2017-09-01 00:00:00
abstract:INTRODUCTION:We examined a 6-month-old girl with inherited fibrinogen abnormality and no history of bleeding or thrombosis. Routine coagulation screening tests showed a markedly low level of plasma fibrinogen determined by functional measurement and also a low level by antigenic measurement (functional/antigenic ratio=...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2014.06.002
更新日期:2014-08-01 00:00:00
abstract:OBJECTIVE:To explore the functional exercises of deep breathing and lower limb motions for the prevention of venous thrombosis in patients undergoing major surgery for gynecologic malignancy. METHODS:All eligible patients admitted to the gynecologic oncology unit were randomized into the study and control groups. A co...
journal_title:Thrombosis research
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.thromres.2019.04.013
更新日期:2019-06-01 00:00:00
abstract:INTRODUCTION:Dermatan sulfate, a sulfated glycosaminoglycan, acts as an anticoagulant by accelerating the inhibition of thrombin by heparin cofactor II. MATERIALS AND METHODS:A low molecular mass dermatan sulfate was obtained by peroxy-radical depolymerization from a parent dermatan sulfate. Chemical characterization ...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2007.09.001
更新日期:2008-01-01 00:00:00
abstract::A B S T R A C T Thrombotic events are a major cause of morbidity and mortality in cancer. While the association of venous thromboembolic events with cancer is well documented, in recent years arterial events (i.e. acute myocardial infarction and ischemic strokes) have also emerged as relatively common complications am...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/S0049-3848(20)30398-4
更新日期:2020-07-01 00:00:00
abstract::Platelet aggregation in platelet-rich plasma (PRP) is more sensitive to agonists and more resistant to antagonists than that in whole blood. In this study, we show that the presence of neutrophils in whole blood accounts at least in part for diminished platelet aggregation in whole blood. The platelet-inhibitory effec...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(90)90216-y
更新日期:1990-12-01 00:00:00
abstract::The effect of activated protein C (APC) on agonist-induced platelet activation and on thrombin generation after intrinsic (IA) and extrinsic (EA) activation of the coagulation system was studied by flow cytometry and by measuring levels of prothrombin fragment F1+2. In platelet activation studies blood drawn from heal...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/s0049-3848(97)00119-9
更新日期:1997-07-15 00:00:00
abstract:INTRODUCTION:Hydrogen sulfide (H2S) known as a gasotransmitter is increasingly recognized for its anti-adhesive, anti-inflammatory and vasoactive properties. Due to these properties, we analysed anti-thrombotic effects of H2S and the participation of the nitric oxide synthase (NOS)-pathway. MATERIALS AND METHODS:In in...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2013.07.010
更新日期:2013-08-01 00:00:00
abstract::Clot dissolution using enzymes from the human fibrinolytic system has long been a goal of physicians and scientists. While recent focus has been on activators of the fibrinolytic system, new data support the use of plasmin itself. This supplement reviews the role of plasmin in fibrinolysis and locally administered pla...
journal_title:Thrombosis research
pub_type:
doi:10.1016/j.thromres.2008.06.008
更新日期:2008-01-01 00:00:00
abstract::To compare Canola a terrestrial (n-3) oil with fish oil (n-3) and common vegetable oil (n-6) in decreasing serum lipids and platelet aggregation, various oils were included in Chow-based diets and fed to rats in an eight-weeks feeding trial. The Chow diet contained 2% cholesterol along with either Canola, menhaden, sa...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(90)90420-h
更新日期:1990-08-01 00:00:00
abstract::Using an ACL 300R coagulometer (Instrumentation Laboratory) we assessed the clinical usefulness of a new method to measure PS activity (PS:Act), based on the prolongation of prothrombin time of a mixture of diluted plasma sample, PS depleted plasma previously incubated with Protac for protein C activation, bovine thro...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(91)90065-5
更新日期:1991-12-15 00:00:00
abstract::Patients with protamine allergy present a difficult dilemma when reversal of heparin is required for excessive bleeding. Premedication with steroids and antihistamines has not been shown to effectively prevent anaphylactic reactions in patients with hypersensitivity to protamine. Other heparin antagonists are either n...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(89)90132-1
更新日期:1989-06-15 00:00:00
abstract::Hemophilia patients with inhibitors against FVIII/FIX present with a major challenge in the clinical practice. In the 1970s such patients were treated in association with emergency situations and essential surgery using huge amounts of FVIII/FIX concentrates often preceded by extracorporal adsorption of antibodies aga...
journal_title:Thrombosis research
pub_type: 历史文章,杂志文章,评审
doi:10.1016/j.thromres.2010.01.021
更新日期:2010-04-01 00:00:00
abstract:INTRODUCTION:Venous thromboembolism (VTE) is a frequent clinical event in patients with gynecologic cancer. However, studies that exclusively address the incidence of VTE according the type of gynecologic cancer are poorly reported. OBJECTIVE:To analyze the incidence of VTE and the associated factors in women with dif...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2019.11.009
更新日期:2020-01-01 00:00:00
abstract::This paper continues our study (see Part I) where we modeled the spatio-temporal dynamics of the intrinsic pathway of blood coagulation. Here, we analyzed this model and showed that it describes the threshold behavior of coagulation. When activation is subthreshold (which produces not more than 0.07 nM factor XIa at s...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/s0049-3848(96)00197-1
更新日期:1996-12-01 00:00:00