Abstract：
:Treatment of bleeding in patients with Glanzmann's thrombasthenia (GT) can be hampered by iso-antibodies against the αIIbβ3 integrin, which cause rapid clearance of transfused donor platelets. Type 1 GT patients with a total absence of αIIbβ3 from the platelet surface are known to be susceptible to form such isoantibodies. In this study, we describe a type 1 GT patient with a missense mutation (Gly540Asn) located in the EGF3 domain of the β3 integrin subunit. Cotransfection analysis in CHO cells demonstrates total absence of αIIbβ3 from the surface, based on inappropriate αIIb maturation. The patient's serum was reactive with αIIbβ3 and αvβ3 integrins in a capture assay, when platelets and endothelial cells were used. Two specificities could be isolated from the patient's serum, anti-αIIbβ3 and anti-αvβ3 isoantibodies. Both specificities did not interfere with platelet aggregation. In contrast, isoantibodies against αvβ3, but not against αIIbβ3, were able to disturb endothelial cell adhesion onto vitronectin, triggered endothelial cell apoptosis and interfered with endothelial tube formation. This intriguing finding may explain more recently observed features of fetal/neonatal iso-immune thrombocytopenia in children from type 1 GT mothers with intracranial haemorrhage, which could be related to anti-endothelial activity of the maternal antibodies. In conclusion, we give evidence that two isoantibody entities exist in type 1 GT patients, which are unequivocally different, both in an immunological and functional sense. Further research on the clinical consequences of immunisation against αvβ3 is required, predominantly in GT patients of childbearing age.
journal_name
Thromb Haemostjournal_title
Thrombosis and haemostasisauthors
Wihadmadyatami H,Röder L,Berghöfer H,Bein G,Heidinger K,Sachs UJ,Santoso Sdoi
10.1160/TH15-12-0982subject
Has Abstractpub_date
2016-08-01 00:00:00pages
262-71issue
2eissn
0340-6245issn
2567-689Xpii
15-12-0982journal_volume
116pub_type
杂志文章abstract：:In a recent study, we purified and cloned a newly identified bioactive factor that stimulates prostacyclin (PGI2) production by vascular endothelial cells (ECs) using conditioned medium (CM) from cultured human diploid fibroblast cells. The present study was undertaken to clarify whether PSF is expressed in ECs and va...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1995-12-01 00:00:00
abstract：:Von Willebrand disease (VWD) is the most common inherited bleeding disorder and is mainly caused by dominant-negative mutations in the multimeric protein von Willebrand factor (VWF). These mutations may either result in quantitative or qualitative defects in VWF. VWF is an endothelial protein that is secreted to the c...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1055/s-0040-1715442
更新日期：2020-11-01 00:00:00
abstract：:Heparin and low molecular weight heparins stimulate two to three fold the accumulation of an antithrombotic heparan sulfate secreted by endothelial cells in culture. This led us to search for the minimum structural requirements of the heparin molecule able to elicit the enhancement of the heparan sulfate. Fragments we...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1995-10-01 00:00:00
abstract：:Autoantibodies to the zwitterionic phospholipid (PL), phosphatidylethanolamine (PE) have been described in patients with thrombotic diseases. Recently, we reported that many antiphosphatidylethanolamine antibodies (aPE) are not specific for PE per se, but are directed to plasma proteins which can bind PE, for example,...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1996-09-01 00:00:00
abstract：:Tissue thromboplastin apoprotein was partially purified from human brain. The apoprotein was recombined with mixed phospholipids to yield active thromboplastin. The recombined thromboplastin induced proteolytic activation of isolated human factor IX in the presence of factor VII and Ca2+. The clotting times of various...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1982-08-24 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 antithrombotic effect of the thromboxane A2 receptor antagonist, vapiprost, was compared with those of other antiplatelet drugs using an arterial thrombosis model which utilized photochemical reaction in the rat femoral artery. Vapiprost prolonged the time required to occlude the artery with thrombus and inhibited...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1992-10-05 00:00:00
abstract：:Five expert laboratories have participated in a cross-laboratory study to co-evaluate and compare three commercial Factor VIII/von Willebrand factor (VWF) concentrates. A total of nine factor concentrate lots were evaluated, comprising AHF (High Purity) (AHF HP; x3), Biostate (x3) and Humate/Haemate (x3). All laborato...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：2002-03-01 00:00:00
abstract：:Bernard-Soulier syndrome is a rare congenital platelet disorder that affects a surface membrane adhesion receptor, glycoprotein (GP) Ib-V-IX. Both the genetic defects and the bleeding diatheses associated with the syndrome are heterogeneous due, in part, to the complexity of the involved receptor which consists of fou...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1996-11-01 00:00:00
abstract：:Edoxaban is an oral direct factor (F)Xa inhibitor in advanced stages of clinical development. The primary objective of the present study was to assess the pharmacodynamics (PD) and safety of enoxaparin 1 mg/kg followed 12 hours (h) post-dose by edoxaban 60 mg, which is the regimen being used in the phase III study of ...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章,随机对照试验
doi：10.1160/TH11-09-0676
更新日期：2012-07-01 00:00:00
abstract：:A new genetic test has been developed for detection of the mutation known as factor V Leiden. The test employs heteroduplex technology and comprises a single PCR reaction followed immediately by PCR product analysis. It therefore represents the minimum practical route from blood/tissue sample to genetic result. A coho...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1997-01-01 00:00:00
abstract：:In this review the interaction between invasive human pathogens expressing plasmin(ogen) receptors and/or producing plasminogen activators with the human plasmin(ogen) system is described. Evidence is presented for multiple mechanisms by which human pathogens can acquire a surface bound form of plasmin that cannot be ...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章,评审
doi：
更新日期：1997-01-01 00:00:00
abstract：:Atherosclerosis is at least in part an inflammatory disease. CD14 is an endotoxin receptor that after binding of lipopolysaccharides evokes endothelial activation and secretion of several cytokines. A polymorphism of CD14 has been associated with myocardial infarction. We evaluated the role of the -159 T/C polymorphis...
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：10.1160/TH03-11-0668
更新日期：2004-05-01 00:00:00
abstract：:Endothelial cell protein C receptor (EPCR) enhances the generation of activated protein C (APC) by the thrombin-thrombomodulin complex. A soluble form of EPCR (sEPCR), which is generated by metalloprotease activity, is present in plasma. The distribution of sEPCR levels in healthy populations is bimodal. Previously, w...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH03-10-0657
更新日期：2004-05-01 00:00:00
abstract：:Both heightened platelet reactivity and an occluded infarct related artery (IRA) on initial angiography and at the time of primary percutaneous coronary intervention (PCI) are associated with a worsened clinical outcome in patients with ST-elevation myocardial infarction (STEMI). However, the relationship between plat...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH10-08-0528
更新日期：2011-08-01 00:00:00
abstract：:After the demonstration that moderate hyperhomocysteinemia is associated with thrombosis, many hematological labs are becoming interested in total homocysteine (tHcy) measurement. This prompted us to organize a collaborative study to investigate the performance of methods used in this setting and to assess the between...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章,多中心研究
doi：
更新日期：2001-02-01 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：:Platelets from a patient with an acquired hemorrhagic disorder had a severely impaired response to collagen, whereas platelet aggregation to other agonists and coagulations tests were normal. No abnormalities of the patient's platelet membrane glycoproteins (GP) were seen. Treatment of the patient with immunosuppressi...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1990-08-13 00:00:00
abstract：:Pulmonary embolism (PE) may encompass a wide spectrum of severity. To determine whether clinical findings, D-dimer (DD) concentration, and deep vein thrombosis (DVT) shown by lower-limb venous compression ultrasonography (US) might predict the scintigraphic extent of PE, we studied 104 hemodynamically stable consecuti...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：2001-11-01 00:00:00
abstract：:Using a monoclonal antibody-based assay, we measured the fibrin degradation product release in the supernatant of plasma clots obtained before and after venous occlusion (VO) in 30 patients with definite or suspected vascular thrombosis (19 definite and 2 suspected deep vein thrombosis, 6 recurrent superficial thrombo...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1990-02-19 00:00:00
abstract：:To assess the thrombotic risk of aprotinin in aortocoronary bypass surgery, we retrospectively analyzed the results of a trial, originally designed to compare the effects of one-year treatment with various antithrombotic drugs in the prevention of vein-graft occlusion. Graft patency at one year was assessed by angiogr...
journal_title：Thrombosis and haemostasis
pub_type： 临床试验,杂志文章,随机对照试验
doi：
更新日期：1996-01-01 00:00:00
abstract：:Platelet-rich plasma was obtained 24 hr after the race ended from athletes who ran in the London marathon. The platelets were only marginally less sensitive to adrenaline than were those of non-runners using conventional aggregation tests. However, the runners' platelets were much more sensitive to inhibition by prost...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1984-07-29 00:00:00
abstract：:The pharmacokinetics of recombinant tissue factor pathway inhibitor (TFPI) after an intravenous bolus injection was studied in rabbits. Clearance of TFPI was followed by measurement of the radioactivity of the 125I-labelled compound in the whole plasma or the trichloroacetic acid precipitate and by quantitation of the...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1992-07-06 00:00:00
abstract：:In eighteen patients with fulminant hepatic failure (FHF), in grade III or IV coma, both protein C antigen and activity were significantly decreased (0.35 +/- 0.03 u/ml and 0.35 +/- 0.03 u/ml respectively). There was a significant correlation between protein C antigen and activity (r = 0.61, p less than 0.01). Protein...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1988-04-08 00:00:00
abstract：:The functional activity and active site of plasmin in full-term newborns have been studied and compared to those in adults in order to investigate the nature of the abnormality found in newborn plasminogen described in a previous paper. The functional activity of newborn plasminogen measured on chromogenic substrate w...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1984-02-28 00:00:00
abstract：:We have previously reported that platelets from bleeding Simmental cattle do not aggregate in vitro in response to ADP, collagen and calcium ionophore A23187, though calcium mobilization and myosin light chain phosphorylation do occur. The aggregation abnormality, measured by aggregometry, was ascribed to abnormal cyt...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1996-12-01 00:00:00
abstract：:Heparin-induced thrombocytopenia (HIT) is an immune-mediated adverse drug reaction that occurs following exposure to unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH). HIT with thrombosis (HITT) can cause devastating venous thromboembolism or arterial clots, prolonged hospitalization, and increased c...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：2008-12-01 00:00:00
abstract：:Clots formed from platelet rich plasma were found to be lysed more readily by low concentrations of pro-urokinase (pro-UK) than clots formed from platelet poor plasma. This was not a non-specific effect since the reverse occurred with tissue plasminogen activator. A mechanical explanation due to platelet-mediated clot...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1994-03-01 00:00:00
abstract：:A new method to determine the concentration of free protein S in plasma is described. It is an enzyme-linked ligandsorbent assay (ELSA) which utilises the protein S binding capacity of the natural ligand C4b-binding protein (C4BP) to capture the free protein S from plasma samples. The use of C4BP as ligand in the assa...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1998-04-01 00:00:00
abstract：:Thrombolytic therapy has become the mainstay of treatment for acute transmural myocardial infarction. Present fibrinolytic regimens have a number of shortcomings, including the failure to induce early and sustained reperfusion in as many as 40-50% of the patients, and to prevent reocclusion in another 10-20% of the pa...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章,评审
doi：
更新日期：1999-09-01 00:00:00
