Abstract:
:Endothelial dysfunction and increased platelet aggregation may be involved in the pathogenesis of normal tissue radiation toxicity. This study assessed clopidogrel, an inhibitor of ADP-induced platelet aggregation, as a modulator of intestinal radiation injury (radiation enteropathy). Rat small intestine was exposed to 21 Gy X-radiation. Clopidogrel (20 mg/kg/day) or vehicle was administered from 2 days before to 10 days after irradiation. Structural radiation injury, neutrophil infiltration, smooth muscle cell proliferation, collagen content, and TGF-beta1 expression were assessed 2 weeks (early phase) and 26 weeks (delayed phase) after irradiation, using quantitative histology and immunohistochemistry, morphometry, and real-time fluorogenic probe RT-PCR. Irradiated intestine exhibited significant histopathologic injury, reduced mucosal surface area, vascular sclerosis, intestinal wall fibrosis, increased collagen content, and increased TGF-beta1 expression. Clopidogrel reduced ADP-induced platelet aggregation by 93% and significantly attenuated the severity of post-radiation vascular sclerosis (p = 0.004 and p = 0.02) and the loss of mucosal surface area (p = 0.0008 and p = 0.003) at both 2 and 26 weeks. Clopidogrel also ameliorated overall histopathologic injury (p = 0.02), relative intestinal collagen content (p = 0.03), and collagen III immunoreactivity levels 2 weeks after irradiation, and caused a borderline reduction in the radiation-induced increase in extracellular matrix-associated TGF-beta immunoreactivity at 26 weeks (p = 0.04). The effects of clopidogrel on steady-state TGF-beta1 mRNA levels and neutrophil infiltration were not statistically significant. Short-term clopidogrel administration affords protection against early and, to a lesser extent, delayed radiation enteropathy. Modulation of platelet aggregation should be subject to further studies as a potential method to increase safety and efficacy of radiation therapy.
journal_name
Thromb Haemostjournal_title
Thrombosis and haemostasisauthors
Wang J,Albertson CM,Zheng H,Fink LM,Herbert JM,Hauer-Jensen Mkeywords:
subject
Has Abstractpub_date
2002-01-01 00:00:00pages
122-8issue
1eissn
0340-6245issn
2567-689Xjournal_volume
87pub_type
杂志文章abstract::A procedure for using citrated fresh plasmas for International Sensitivity Index (ISI) calibration of two types of whole blood point-of-care test (POCT) prothrombin time (PT) monitor systems has been assessed in a multicentre study. The CoaguChek Mini and TAS PT-NC systems gave higher ISI with whole blood samples than...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,多中心研究
doi:
更新日期:2002-05-01 00:00:00
abstract::Parameters of the fibrinolytic system were studied in a primate model where the generation of thrombin was promoted in vivo. The procoagulant stimulus used was a combination of human factor Xa in combination with phosphatidylcholine/phosphatidylserine lipid vesicles (PCPS) as the source of coagulant active phospholipi...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1990-06-28 00:00:00
abstract::Protein C is an important inhibitor of blood coagulation. We investigated the effect of two polymorphisms within the promoter region of the protein C gene (C/T at position 2405 and A/G at position 2418) on risk of venous thrombosis and on plasma protein C levels. In addition the combined effect of the two polymorphism...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:2009-01-01 00:00:00
abstract::Duplex ultrasound is the first-line diagnostic test for detecting lower limb deep-vein thrombosis (DVT) but it is time consuming, requires patient transport, and cannot be interpreted by most physicians. The accuracy of emergency physician-performed ultrasound (EPPU) for the diagnosis of DVT, when performed at the bed...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,meta分析,评审
doi:10.1160/TH12-07-0473
更新日期:2013-01-01 00:00:00
abstract::Intraluminal thrombus formation in aortic abdominal aneurysms (AAA) is associated with adverse clinical prognosis. Interplay between coagulation and inflammation, characterised by leukocyte infiltration and cytokine production, has been implicated in AAA thrombus formation. We studied leukocyte (CD45+) content by flow...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH12-05-0339
更新日期:2012-11-01 00:00:00
abstract::Neonatal platelets are hypo-reactive to the tyrosine kinase-linked receptor agonist collagen. Here, we have investigated whether the hypo-responsiveness is related to altered levels of glycoprotein VI (GPVI) and integrin α2β1, or to defects in downstream signalling events by comparison to platelet activation by C-type...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1055/s-0038-1646924
更新日期:2018-06-01 00:00:00
abstract::We investigated plasma activated factor VII (FVIIa) levels in uremic patients (nondialysis group: n = 38; dialysis group: n = 36) and healthy controls (n = 32). We also measured the plasma levels of thrombomodulin (an indicator of endothelial cell injury) and tissue factor. Plasma FVIIa showed a marked increase in the...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1995-05-01 00:00:00
abstract::Vascular endothelial growth factor (VEGF) is a mitogen for endothelial cells. We have studied the production of VEGF by human macrophages in response to lipopolysaccharide (LPS). Macrophages stimulated with LPS expressed VEGF mRNA and protein in concentration- and time-dependent manners. The LPS-induced expression of ...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:2001-01-01 00:00:00
abstract::Hemophilia B is a sex-linked recessive bleeding disorder characterized by the presence of either a decreased amount of normal factor IX (FIX) or the presence of a dysfunctional FIX. We have identified a unique mutation in a family with mild hemophilia B. DNA analysis of family members revealed a single base transition...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:2001-09-01 00:00:00
abstract::The optimal long-term treatment of acute venous thromboembolism (VTE) in patients with malignancy remains undefined. In particular, based on current evidence, it is uncertain whether secondary prophylaxis using standard intensity oral anticoagulant therapy is associated with higher risks of bleeding and recurrent thro...
journal_title:Thrombosis and haemostasis
pub_type: 临床试验,杂志文章,多中心研究
doi:
更新日期:2000-11-01 00:00:00
abstract::Evaluation of factor F(V)III replacement in patients with haemophilia A undergoing surgery is critical for FVIII concentrates, yet large scale, multi-center prospective studies, particularly using continuous infusion, are generally lacking for new products. This study evaluated efficacy and safety of a newly developed...
journal_title:Thrombosis and haemostasis
pub_type: 临床试验,杂志文章,多中心研究
doi:
更新日期:2008-08-01 00:00:00
abstract::Antiphospholipid-protein antibodies (APA) are a family of immunoglobulins which have been defined by varying laboratory test systems. Lupus anticoagulants (LA) and anticardiolipin antibodies (ACA) are the two most prominent members of this family of antibodies. LA are detected utilizing various phospholipid (PL) depen...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,评审
doi:
更新日期:1995-07-01 00:00:00
abstract::The liver can be injured and its functions altered by activation of the coagulation and inflammatory processes in sepsis. The objective of the present study was to investigate the pattern of protease- activated receptors (PARs) over time in a model of acute liver injury induced by lipopolysaccharide (LPS); and whether...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:2006-12-01 00:00:00
abstract::The development of antibodies against infused factor VIII (FVIII) in patients with haemophilia A is a serious complication leading to poorly controlled bleeding and increased morbidity. No treatment has been proven to reduce high titre antibodies in patients who fail immune tolerance induction or are not candidates fo...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,多中心研究
doi:10.1160/TH14-01-0078
更新日期:2014-09-02 00:00:00
abstract::An algal sulfated galactan has high anticoagulant and antithrombotic activities. Its serpin-dependent anticoagulant action is due to promoting thrombin and factor (F)Xa inhibition by antithrombin and heparin cofactor II. Here, we evaluated the anticoagulant effect of the algal sulfated galactan using serpin-free plasm...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH09-04-0273
更新日期:2009-12-01 00:00:00
abstract::In health, haemostasis and angiogenesis are tightly regulated processes, but may become deregulated in cancer. Recent evidence suggests that platelet activation may link these processes as platelets can release angiogenic factors such as vascular endothelial growth factor (VEGF). Furthermore, inflammation has also bee...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH03-11-0679
更新日期:2004-07-01 00:00:00
abstract::Without thromboprophylaxis, knee arthroscopy (KA) carries a low to moderate risk of venous thromboembolism. Over 5 million arthroscopies are performed worldwide yearly. It was our study objective to assess the efficacy and safety of rivaroxaban for thromboprophylaxis after therapeutic KA. Patients undergoing KA in nin...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1160/TH16-02-0118
更新日期:2016-08-01 00:00:00
abstract:BACKGROUND: A strong association between on-thienopyridine platelet reactivity (PR) and the risk of both thrombotic and bleeding events in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI) has been demonstrated. However, no study has analyzed the relationship between on-ticagrel...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1055/a-1326-5110
更新日期:2020-12-01 00:00:00
abstract::This study was undertaken to appraise the application of those reagents most widely used in the UK for the detection and confirmation of lupus anticoagulant (LA) on an Amelung KC4A and a Sysmex CA-6000 coagulometer. Five sets of dilute Russell's viper venom time (DRVVT) reagents were assessed as well as the Textarin-P...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1999-05-01 00:00:00
abstract::Abnormalities of Hageman factor dependent pathways have been described in a wide variety of human disease states. Congenital deficiencies of factor XII (Hageman trait) prekallikrein (Fletcher trait) and high molecular weight kininogen (Williams, Fitzgerald and Flaujeac traits) although resulting in profound in vitro c...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,评审
doi:
更新日期:1977-12-15 00:00:00
abstract::The significance of platelet beta-adrenoceptors for platelet responses to adrenergic stimuli in vivo and in vitro was studied in healthy volunteers. Low dose infusion of the beta-adrenoceptor agonist isoprenaline decreased platelet aggregability in vivo as measured by ex vivo filtragometry. Infusion of adrenaline, a m...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1992-12-07 00:00:00
abstract::Despite reports that Tris [tris (hydroxymethyl)aminomethane] affects platelets, it is often used to buffer suspending media. Human or rabbit platelets were washed and resuspended in Tyrode solution containing apyrase and 0.35% albumin. Addition of 15 mM Tris partially inhibited primary aggregation induced by 10 microM...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1984-04-30 00:00:00
abstract::Cultured human mesangial cells (HMC) derived from normal kidneys have been shown to synthesize tissue-type plasminogen activator (t-PA) and excess amounts of PA inhibitor type 1 (PAI-1). Conflicting results have been obtained concerning the production of urokinase-type PA (u-PA) and efforts to show PA inhibitor 2 (PAI...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1995-12-01 00:00:00
abstract::Coronary artery disease (CAD) is a multifactorial disease, and family history is the best available tool to assess gene-environment interaction. This study addressed the heritability of quantitative traits, namely lipid, coagulation/fibrinolysis and pro-inflammatory markers in the ongoing family-based Indian Atheroscl...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH08-01-0018
更新日期:2009-08-01 00:00:00
abstract::Kawasaki disease (KD) is an acute systemic vasculitis causing coronary arterial aneurysms and myocardial infarction in young children. Prominent thrombocytosis with increased megakaryocytes develops during the convalescent period. To clarify the mechanisms of thrombocytosis, we studied serum levels of thrombopoietin (...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1998-06-01 00:00:00
abstract::The leech protein hirudin is a potent inhibitor of thrombin, but clinical use of recombinant hirudin is restricted by haemorrhagic risks, and complicated by hirudin's rapid clearance from the circulation. We previously employed albumin fusion to slow hirudin variant 3 (HV3) clearance. In this study, we hypothesized th...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:2009-05-01 00:00:00
abstract::The endothelial barrier of the vasculature is of utmost importance for separating the blood stream from underlying tissues. This barrier is formed by tight and adherens junctions (TJ and AJ) that form intercellular endothelial contacts. TJ and AJ are integral membrane structures that are connected to the actin cytoske...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,评审
doi:10.1160/TH14-04-0298
更新日期:2015-01-01 00:00:00
abstract::The clinical severity in some patients with haemophilia A appears to be unrelated to the levels of factor (F)VIII activity (FVIII:C), but mechanisms are poorly understood. We have investigated a patient with a FVIII gene mutation at Arg1781 to His (R1781H) presenting with a mild phenotype despite FVIII:C of 0.9 IU/dl....
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH12-10-0762
更新日期:2013-06-01 00:00:00
abstract::Mouse C127 epithelioid cells were genetically engineered to produce biologically active gamma-carboxylated human protein S. A full length human protein S cDNA was cloned into a bovine papilloma virus (BPV) based shuttle vector under the transcriptional control of the Moloney murine sarcoma virus enhancer and the mouse...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1992-05-04 00:00:00
abstract::Microparticles (MPs) are formed from platelets (PMPs), endothelial cells (EMPs) and monocytes (MMPs), and in acute myocardial infarction (MI), there is an increase of MPs in the culprit artery. In this study MPs were evaluated in whole blood in 105 patients with MI at five time-points during a two-year follow-up (FU)....
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH16-11-0837
更新日期:2017-07-26 00:00:00