Abstract:
:Despite great efforts in stroke research, disability and recurrence rates in ischaemic stroke remain unacceptably high. To address this issue, one potential target for novel therapeutics is the glycoprotein von Willebrand factor (vWF), which increases in thrombogenicity especially under high shear rates as it bridges between vascular sub-endothelial collagen and platelets. The rationale for vWF as a potential target in stroke comes from four bodies of evidence. (1) Animal models which recapitulate the pathogenesis of stroke and validate the concept of targeting vWF for stroke prevention and the use of the vWF cleavage enzyme ADAMTS13 in acute stroke treatment. (2) Extensive epidemiologic data establishing the prognostic role of vWF in the clinical setting showing that high vWF levels are associated with an increased risk of first stroke, stroke recurrence or stroke-associated mortality. As such, vWF levels may be a suitable marker for further risk stratification to potentially fine-tune current risk prediction models which are mainly based on clinical and imaging data. (3) Genetic studies showing an association between vWF levels and stroke risk on genomic levels. Finally, (4) studies of patients with primary disorders of excess or deficiency of function in the vWF axis (e.g. thrombotic thrombocytopenic purpura and von Willebrand disease, respectively) which demonstrate the crucial role of vWF in atherothrombosis. Therapeutic inhibition of VWF by novel agents appears particularly promising for secondary prevention of stroke recurrence in specific sub-groups of patients such as those suffering from large artery atherosclerosis, as designated according to the TOAST classification.
journal_name
Thromb Haemostjournal_title
Thrombosis and haemostasisauthors
Buchtele N,Schwameis M,Gilbert JC,Schörgenhofer C,Jilma Bdoi
10.1055/s-0038-1648251subject
Has Abstractpub_date
2018-06-01 00:00:00pages
959-978issue
6eissn
0340-6245issn
2567-689Xjournal_volume
118pub_type
杂志文章,评审abstract::Monitoring of anti-factor Xa activity is often performed during treatment with low-molecular-weight heparins (LMWHs) in pregnancy because the anticoagulant effect may decrease as pregnancy progresses, but assays for anti-factor Xa activity are unavailable in many clinical institutions caring for pregnant women. Heptes...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH08-09-0560
更新日期:2009-11-01 00:00:00
abstract::We have previously suggested that the human homologue of the Drosophila transient receptor potential protein, TRPC1, is involved in conducting store-operated Ca2+ entry (SOCE) in human platelets since an antibody raised against the pore-forming region of TRPC1 inhibited SOCE. Here we have investigated plasma membrane ...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH05-06-0391
更新日期:2005-10-01 00:00:00
abstract::Risk scores in patients with atrial fibrillation (AF) based on clinical factors alone generally have only modest predictive value for predicting high risk patients that sustain events. Biomarkers might be an attractive prognostic tool to improve bleeding risk prediction. The new ABC-Bleeding score performed better tha...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH17-07-0478
更新日期:2017-10-05 00:00:00
abstract::Inherited thrombophilic states are associated with an increased risk for deep vein thrombosis (DVT), but whether they are also risk factors for superficial vein thrombosis (SVT) is uncertain. We assessed the risk conferred by inherited thrombophilic states in patients with a first episode of SVT in whom the coexistenc...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1999-10-01 00:00:00
abstract::The antithrombotic efficacies of the coagulation factor Xa inhibitor recombinant tick anticoagulant peptide (rTAP) and heparin were compared in a canine model of left circumflex (LCX) coronary artery electrolytic lesion. Intravenous infusions of saline (controls), rTAP (50 micrograms/kg/min continuous infusion) or hep...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1995-08-01 00:00:00
abstract::There is much debate over the appropriateness of prescribing prolonged anticoagulation to heterozygous carriers of factor V Leiden suffering a first episode of deep vein thrombosis (DVT). We, thus used meta-analysis to estimate from six eligible studies the summary odds-ratio of recurrent DVT in carriers of factor V L...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:2000-11-01 00:00:00
abstract::A model has been developed to study the transport of fluid and macromolecules through human arterial umbilical cord endothelial cell monolayers in vitro. Cells were cultured on fibronectin-coated polycarbonate filters and formed within a few days a tight monolayer, with an electrical resistance of 17 +/- 4 Ohm.cm2. Th...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1988-10-31 00:00:00
abstract::The cloning of the cDNA encoding von Willebrand factor (vWF) has revealed that it is synthesized as a large precursor (pre-pro-vWF) molecule and it is now clear that the prosequence or vWAgII is responsible for the intracellular multimerization of vWF. We have cloned the complete vWF cDNA and expressed it using a reco...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1992-01-23 00:00:00
abstract::Tissue factor (TF) markedly enhances the ability of factor VIIa (FVIIa) to cleave both macromolecular and small peptidyl substrates. Using soluble mutant TF (sTF) to investigate TF-enhanced FVIIa amidolytic activity in solution, we screened thirty-four commercially available peptidyl-p-nitroanilide substrates and foun...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1993-12-20 00:00:00
abstract::Tissue factor-factor VIIa catalysed activation of factor IX is inhibited by the complex of tissue factor pathway inhibitor (TFPI) and factor Xa. At present, no information is available as to what extent the kinetics of complex formation between TFPI and factor Xa during factor X activation contribute to the overall ra...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1995-09-01 00:00:00
abstract::Integrins are cell surface adhesion receptors that participate in a variety of important processes throughout the vasculature. Here we summarize some recent findings on the regulation of integrin mediated cellular adhesion. Particular emphasis is placed on the regulation of integrin affinity for ligand (activation), a...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,评审
doi:
更新日期:2001-07-01 00:00:00
abstract::Molsidomine and its active metabolite SIN-1 were examined in humans and animals for platelet suppressant and fibrinolytic activities. Following oral administration of molsidomine at doses of 6 or 15 mg/kg to rabbits, their blood platelets in PRP ex vivo required higher threshold concentrations of ADP, AA and thrombin ...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1985-12-17 00:00:00
abstract::High heparin cofactor II (HCII) activity has recently been described to protect from coronary instent restenosis, presumably by inactivating thrombin in injured arteries. In this study, we investigated the association of HCII activity and restenosis after femoropopliteal stenting. We studied 63 consecutive patients wi...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH04-05-0311
更新日期:2004-11-01 00:00:00
abstract::Plasmin triggers chemotaxis and NF-kappa B- and AP-1-mediated proinflammatory gene expression in human peripheral monocytes (PM). Compared with macrophages and dendritic cells, PM express mainly the peroxisome proliferator-activated receptor (PPAR) gamma and traces of PPAR alpha as detected by semiquantitative RT-PCR ...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:2002-08-01 00:00:00
abstract::Haemostatic parameters were assessed before insulin induced hypoglycaemia and 0, 1 and 2 hr after discontinuation of insulin infusion in 7 non-diabetics, aged 28 (22-31) years (mean and range), and 8 juvenile diabetics, aged 31 (27-35) years, with a mean duration of diabetes of 4 years. The patients were normoglycaemi...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1982-06-28 00:00:00
abstract::Normal adults have very few circulating endothelial cells (CECs) in their blood, but increased levels have been shown in association with conditions associated with endothelial damage such as myocardial infarction and stroke. As atrial fibrillation (AF) is associated with a hypercoagulable state and abnormalities of p...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH05-02-0093
更新日期:2005-10-01 00:00:00
abstract::In the last decades, substantial progress has been made in understanding the relationship between lipid disorders and prevention of cardiac ischemic disease. Statins competitively inhibit 3-hydroxyl-3-methylglutaryl coenzyme A (HMG-CoA) reductase, an enzyme crucial to cholesterol biosynthesis. Statins have long been t...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,评审
doi:10.1160/TH03-04-0249
更新日期:2003-10-01 00:00:00
abstract::Thirty-two patients with acute, proximal-vein thrombosis were treated with heparin and alteplase (0.25 versus 0.5 mg/kg/24 h during 3-7 days) in a randomized, double-blind, multicenter, European (ETTT) trial. The treatment resulted in a decrease of the venographic Marder's score from 18 (6-25) to 13 (2-24) units (medi...
journal_title:Thrombosis and haemostasis
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:
更新日期:1992-03-02 00:00:00
abstract::Thrombin-induced platelet release reaction examined with secretion of calcium and N-acetylglucosaminidase was significantly enhanced in the platelets from reserpine-treated rabbits as compared with the control. On the other hand, 32P-incorporation into phosphatidic acid was suppressed in the reserpinized platelets in ...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1983-08-30 00:00:00
abstract::Myocardial infarction results from a platelet-rich occlusive coronary thrombus. Platelet membrane glycoprotein IIb/IIIa plays an important role in platelet adhesion and aggregation. Two polymorphisms of the gene encoding the IIIa subunit. PLA1 and PLA2, have been identified. We investigated the frequency of these poly...
journal_title:Thrombosis and haemostasis
pub_type: 临床试验,杂志文章
doi:
更新日期:1998-08-01 00:00:00
abstract::This review collects evidence about immune and inflammatory functions of platelets from a clinician's point of view. A focus on clinically relevant immune functions aims at stimulating further research, because the complexity of platelet immunity is incompletely understood and not yet translated into patient care. Pla...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,评审
doi:10.1160/TH14-02-0146
更新日期:2014-10-01 00:00:00
abstract::Staphylokinase (SAK) expresses plasminogen activator (PA) activity by forming a complex with plasmin. The interaction between the plasmin-SAK complex and plasminogen was investigated using synthesized peptides, which were constructed according to the amino acid sequence of the SAK molecule. A synthetic nonadecapeptide...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:2007-05-01 00:00:00
abstract::Antiphospholipid antibodies (aPL) have been associated with thrombosis and pregnancy losses in patients diagnosed with antiphospholipid syndrome (APS) and enhance thrombus formation in vivo in mice, but the mechanism of thrombosis by aPL is not completely understood. It has been proposed that aPL may affect endothelia...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:2000-09-01 00:00:00
abstract::The frequency of heterozygous protein C and protein S deficiency, detected by measuring total plasma antigen, in a group (n = 141) of young unrelated patients (less than 45 years old) with venous thrombotic disease was studied and compared to that of antithrombin III, fibrinogen, and plasminogen deficiencies. Among 91...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1988-02-25 00:00:00
abstract::A method is described for increasing the sensitivity of the thiobarbiturate assay for malondialdehyde by concentrating the coloured reaction product. The basal level of malondialdehyde-like material in plasma was found to be about 0.03 micrometer. Platelets synthesized malondialdehyde when stimulated by collagen or th...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1977-12-15 00:00:00
abstract::The vast majority of thrombin (>95%) is generated after clotting is completed, suggesting that thrombin formation serves purposes beyond coagulation, such as tissue repair after vessel injury. Two types of vascular thrombin binding sites exist: protease-activated receptors (PARs) and thrombomodulin (TM). Their express...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,评审
doi:10.1160/TH09-09-0627
更新日期:2010-05-01 00:00:00
abstract::Seven healthy male volunteers were subjected to exercise of short (STR; 1.7 km), middle (MTR; 4.8 km) and long (LTR; 10.5 km) term runs at a speed close to maximal capacity. Blood samples were drawn before, immediately after exercise and at intervals over the next 10 h. FVIIIR:Ag (von Willebrand factor) rose 2.2-3.2 f...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1990-11-30 00:00:00
abstract::Post-infusion hepatitis is known to occur very frequently in haemophiliacs after treatment with unheated commercial clotting factor concentrates, obtained from large plasma donation pool. On the contrary, single-donor cryoprecipitate is likely to carry a lower risk of transmitting hepatitis. To evaluate this hypothesi...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1986-12-15 00:00:00
abstract::Staphylokinase is a potent highly fibrin-selective thrombolytic agent, but it induces a humoral immune response in most treated patients. Staphylokinase-specific T-lymphocytes can be found in normal healthy individuals, from whom a large panel of staphylokinase-specific T-cells were cloned. The staphylokinase amino ac...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:2002-04-01 00:00:00
abstract::Heparanase is implicated in angiogenesis and tumour progression. We previously demonstrated that heparanase might also affect the haemostatic system in a non-enzymatic manner. It forms a complex and enhances the activity of the blood coagulation initiator tissue factor (TF). Peptides that we generated from TF pathway ...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH16-02-0119
更新日期:2016-09-27 00:00:00