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 against FVIII/FIX. However, moderate to mild bleedings were not effectively treated. A certain hemostatic effect of activated prothrombin complex concentrates (aPCC) not exceeding 65% was reported. Unfortunately, also thromboembolic events occurred, which made them less attractive to use in inhibitor patients. In a dog model the thrombogenic effects on the coagulation system was almost completely avoided by adding antithrombin and heparin, suggesting factors like IXa, Xa or XIa to be responsible. On the other hand FVIIa is not readily inactivated by antithrombin in the circulation. Furthermore, a detailed literature review revealed very high levels of FVII in the aPCC used with some success in the treatment of hemophilia patients with inhibitors. The potential possibility to use FVIIa as a hemostatic agent was investigated by the administration of pure human FVIIa to two hemophilia patients with inhibitors. In both, a hemostatic effect was recorded. The development of recombinant FVIIa was initiated by Novo Nordisk A/S, Denmark, in June 1986 resulting in NovoSeven (rFVIIa) being licensed for use in patients with inhibitors against coagulation factors in EU in 1996. By then, a hemostatic effect of rFVIIa also in non-hemophilia patients such as patients with platelet dysfunctions or suffering from profuse, heavy bleedings initiated by extensive surgery or trauma had been demonstrated. In parallel the mechanism of action of pharmacological doses of rFVIIa was investigated resulting in a revision of the hemostatic process in stressing the compartmentalization of the process to TF-bearing cells and to thrombin activated platelets at the site of injury. The initial thrombin generation is generated by the formation of the TF-FVIIa-complex formed initially on the TF-bearing cells.
journal_name
Thromb Resjournal_title
Thrombosis researchauthors
Hedner Udoi
10.1016/j.thromres.2010.01.021subject
Has Abstractpub_date
2010-04-01 00:00:00pages
S4-6eissn
0049-3848issn
1879-2472pii
S0049-3848(10)00074-5journal_volume
125 Suppl 1pub_type
历史文章,杂志文章,评审abstract::We have investigated the role of platelet activating factor (PAF) in the pathogenesis of a murine model of traumatic shock using WEB 2086, a specific antagonist of PAF. WEB 2086 (0.5 mg/kg) significantly reversed the decrease in mean arterial blood pressure (MABP) induced by PAF (0.3 micrograms/kg) in anesthetized rat...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(89)90107-2
更新日期:1989-02-01 00:00:00
abstract::The experiments in this work were focused on determination of the extent to which fibrinogen component of fibrin glue (Hemaseel HMN, Haemacure Biotech.) retained the conformation of the parent molecule after dry heat antiviral treatment (one hour at 100 degrees C). For this purpose antigenic structure of the fibrinoge...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(96)00084-9
更新日期:1996-05-15 00:00:00
abstract::The hemolytic uremic syndrome involves the presence of Shiga toxin producing strains of Escherichia coli and is associated with thrombocytopenia, platelet activation, and microthrombi formation. We have, therefore, investigated the ability of Shiga toxin isotypes 1 and 2 to cause or enhance platelet aggregation under ...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/s0049-3848(00)00191-2
更新日期:2000-06-01 00:00:00
abstract::The zymogen form of circulating Factor VII activating protease (FSAP) is activated by histones that are released as a consequence of tissue damage or excessive inflammation. This is likely to have consequences in a number of disease conditions such as stroke, atherosclerosis, liver fibrosis, thrombosis and cancer. To ...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2019.08.016
更新日期:2019-10-01 00:00:00
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
更新日期:1999-11-15 00:00:00
abstract:INTRODUCTION:Clinical trials have provided evidence about efficacy and safety of extended thromboprophylaxis among total hip replacement (THR) patients. There is a lack of evidence on effectiveness and safety of extended treatment in unselected patients from routine clinical practice. We examined the effectiveness and ...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2014.11.029
更新日期:2015-02-01 00:00:00
abstract::Intra-ventricular hemorrhage (IVH) occurs predominantly in very low birth weight premature infants. Survivors of severe IVH frequently experience long-term consequences including major neurological deficits. Advances in neonatal and obstetric care in the last decades, have led to a steady decline in mortality and in t...
journal_title:Thrombosis research
pub_type: 杂志文章,评审
doi:10.1016/S0049-3848(11)70032-9
更新日期:2011-02-01 00:00:00
abstract::Surviving an embolism exposes patients to potential long-term complications, such as altered quality of life, persistent dyspnea, impaired exercise capacity or pulmonary hypertension. The common objective factor in most of these situations is the presence of residual pulmonary vascular obstruction (RPVO). Planar venti...
journal_title:Thrombosis research
pub_type: 杂志文章,评审
doi:10.1016/j.thromres.2019.09.038
更新日期:2019-12-01 00:00:00
abstract:INTRODUCTION:Management of pregnant women at risk for venous thromboembolism (VTE) remains complex. Guidelines do not definitively fix optimal strategies due to limited trial data. Our objective was to build an easy-to-use tool allowing individualised, risk-adapted prophylaxis. MATERIALS AND METHODS:A Delphi exercise ...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2010.01.012
更新日期:2010-08-01 00:00:00
abstract:INTRODUCTION:We showed previously that the prothrombotic effect of one hour aldosterone (ALDO) infusion in rats was only partially mediated by the mineralocorticoid receptor (MR). Bearing in mind that ALDO potentiates the effects of angiotensin II (Ang II), in the present study we investigated the role of Ang II recept...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2015.12.008
更新日期:2016-02-01 00:00:00
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. M...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2005.11.015
更新日期:2006-01-01 00:00:00
abstract::Flavocetin-A is a strong platelet aggregation inhibitor isolated from the venom of Trimeresurus flavoviridis. It binds specifically to platelet glycoprotein Ib with high affinity and inhibits von Willebrand factor-dependent platelet aggregation. The apparent molecular weight of flavocetin-A is 149 kDa. It consists of ...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/s0049-3848(00)00234-6
更新日期:2000-08-01 00:00:00
abstract::G619, a 4-OH-isophthalic acid derivative, was studied for its capacity to inhibit platelet aggregation. G619 dose-dependently inhibited U46619, collagen, ADP, PAF, thrombin and epinephrine-induced platelet aggregation in vitro. The IC50 values for inhibition of U46619-induced human and rabbit platelet aggregation were...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(92)90283-g
更新日期:1992-05-15 00:00:00
abstract::Activation of plasma plasminogen to plasmin is the objective of current strategies for thrombolytic therapy. Although thrombolytic activity in blood involves a large cellular component as well as that in plasma, the contribution of this cellular phase to clinical thrombolysis has not been examined. Using a 125I-fibrin...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(90)90128-y
更新日期:1990-07-15 00:00:00
abstract::1 g acetyl salicylic acid orally significantly enhanced the initial rate of platelet aggregation induced by 1 mumol/l and 2.5 mumol/l ADP. Sodium salicylate was without effects on the platelet aggregation and specifically it did not prevent acetylsalicylic acid from inhibiting the secondary aggregation. Sodium salicyl...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(85)90212-9
更新日期:1985-06-15 00:00:00
abstract::The effect of several vitamin K (Vit K) analogues on the aggregation of human platelets was examined. The analogues were potent inhibitors of aggregation induced by ADP, thrombin, collagen and arachidonate but were less active against aggregation induced by the calcium ionophore A23187. Vit K3 also prevented platelet ...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(85)90037-4
更新日期:1985-01-01 00:00:00
abstract:INTRODUCTION:Thrombotic storm (TS) presents as a severe, acute thrombotic phenotype, characterized by multiple clotting events and frequently affecting younger adults. Understanding the extensive hypercoagulation of an extreme phenotype as TS will also provide insight into the pathogenesis of a wider spectrum of thromb...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2017.11.016
更新日期:2018-01-01 00:00:00
abstract::Recent studies have demonstrated that neutrophilic granulocytes and platelets have the capability to interact with each other. Either type of cell may release soluble factors, which either activate the other or increase its response to separate stimulating agents. Direct contact between the two types of cell generally...
journal_title:Thrombosis research
pub_type: 杂志文章,评审
doi:10.1016/s0049-3848(10)80002-7
更新日期:1994-01-01 00:00:00
abstract::The inability of the heparin-antithrombin complex to inhibit fibrin-bound thrombin limits the utility of heparin for treatment of arterial thrombosis. In contrast with heparin, melagatran, a direct thrombin inhibitor (DTI), is equally effective at inhibiting fluid-phase thrombin and thrombin bound to fibrin. This refl...
journal_title:Thrombosis research
pub_type: 杂志文章,评审
doi:10.1016/s0049-3848(03)00251-2
更新日期:2003-07-15 00:00:00
abstract::The extracellular nucleotides, ATP and ADP, as well as adenosine have been implicated in a great number of physiological functions. ADP is one of the major platelet recruiting factors, whereas ATP is considered to be a competitive inhibitor of ADP-induced platelet aggregation and adenosine is able to induce vasodilata...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2007.01.006
更新日期:2007-01-01 00:00:00
abstract::Coronary artery disease (CAD) continues to be the most frequent cause of death among women in the United States. Although elevated levels of clotting factors have been associated with CAD, few of these studies have been performed in women. Elevated levels of Factor XI have previously been associated with venous thromb...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/s0049-3848(02)00190-1
更新日期:2002-07-15 00:00:00
abstract::There is a close interrelation between cancer and haemostasis, which is characterized by changes in the haemostatic system, mostly an activation of coagulation in cancer patients. Venous thromboembolism (VTE) is a frequent complication of cancer and in particular of anticancer therapy and is associated with significan...
journal_title:Thrombosis research
pub_type: 杂志文章,评审
doi:10.1016/S0049-3848(10)70005-0
更新日期:2010-04-01 00:00:00
abstract:OBJECTIVES:Dabigatran etexilate is widely used for stroke prevention in the patients with atrial fibrillation. The anticoagulation activity of dabigatran is not necessary monitored in routine clinical practice. We aimed to study the effect of dabigatran on thrombin generation (TG) and coagulation assays in rabbit and h...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2018.03.012
更新日期:2018-05-01 00:00:00
abstract::Four murine monoclonal antibodies against rat platelets were produced by fusion of spleen cells from mice intravenously immunized with whole rat platelets. All four antibodies immunoprecipitated two major platelet membrane proteins with apparent molecular weights of 130,000 and 82,000 (nonreduced) and of 120,000 and 9...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(90)90118-v
更新日期:1990-09-15 00:00:00
abstract:INTRODUCTION:The epidemiology of tamoxifen and venous thromboembolism (VTE) is not well understood, and most data on tamoxifen toxicity are from adjuvant clinical trials. This study examined the relationship between the duration of tamoxifen use in female patients with breast cancer and the risk of VTE in a large popul...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2011.11.025
更新日期:2012-07-01 00:00:00
abstract:BACKGROUND:Sampling small volumes of blood may be necessary, particularly in pediatric patients, or in case of difficult or recurrent venipunctures. METHODS:Routine hemostasis test results evaluated in partial- and full-draw evacuated polymer tubes obtained in 4 centers were compared. RESULTS:No relevant discrepancy ...
journal_title:Thrombosis research
pub_type: 杂志文章,多中心研究
doi:10.1016/j.thromres.2010.08.029
更新日期:2010-12-01 00:00:00
abstract:INTRODUCTION:Prediction of venous thromboembolism (VTE) occurrence in cancer patients using individual risk factors may contribute to preventing the burden of disease associated with VTE. Congestive heart failure in patients with cancer may increase the risk of VTE and worsen the prognosis. AIM:We sought to investigat...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/S0049-3848(16)30134-7
更新日期:2016-04-01 00:00:00
abstract:INTRODUCTION:A paradox seems to exist: exercising leads to clotting activation in conventional clotting tests, but exercising persons have a low risk of thrombosis. In this study we tried to evaluate the effect of exercise performance status on in vitro plasma thrombin generation, which represents an overall function t...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2013.04.009
更新日期:2013-06-01 00:00:00
abstract:INTRODUCTION:Lung cancer is the leading cause of cancer-related death worldwide. Small cell lung cancer (SCLC) is thereby a highly aggressive neuroendocrine carcinoma representing about 15% of all lung cancer cases. Due to the highly metastatic behavior and multidrug resistance, the long-term survival of patients is ve...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/S0049-3848(16)30166-9
更新日期:2016-04-01 00:00:00
abstract::D-dimer of human fibrin was used as antigen to obtain monoclonal antibodies (mAbs). We have obtained 16 hybridomas producing mAbs of different specificity. Only two of these mAbs inhibited fibrin polymerization. They are of the IgG-class. One mAb (II-4d) inhibited fibrin polymerization to 100% and another (II-3b) to 6...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2004.03.005
更新日期:2004-01-01 00:00:00