Abstract：
:Antiphospholipid antibodies (aPL) have been reported to activate platelets. This is considered to be one of the pathogenic properties of aPL. Even though aPL heterogeneity is quite well established, little is known, if the ability to activate platelets is common to all aPL or depends on antigen specificity. To further study this issue, we analyzed the ability of three human monoclonal aPL with distinctly different antigenic specificities to activate platelets in vitro. The results obtained with human monoclonal aPL were validated with immunoglobulin G (IgG) fractions obtained from patients with antiphospholipid syndrome (APS). A co-factor-independent human monoclonal anticardiolipin aPL had no discernible effect on human platelets. Two monoclonal aPL reactive against β2 glycoprotein I (β2GPI) induced platelet aggregation, integrin αIIbβ3 activation and P-selectin surface expression. These data could be confirmed with patient IgG fractions which could only induce aggregation, if they had anti-β2GPI activity. Anti-β2GPI aPL-induced platelet activation depended on interaction of aPL with the low affinity Fcγ-receptor IIa on the platelet surface. It was completely abolished by pretreatment of platelet-rich plasma with the mechanistic target of rapamycin (mTOR) inhibitors rapamycin or everolimus. This extends previous data showing that mTOR is involved in signaling of anti-β2GPI in monocytes and endothelial cells. In conclusion, anti-β2GPI aPL activate platelets while co-factor-independent anticardiolipin aPL have no effect. mTOR is involved in this signaling process which has implications beyond APS, because so far the role of mTOR signaling in platelets is incompletely explored and requires further study.
journal_name
Thromb Haemostjournal_title
Thrombosis and haemostasisauthors
Hollerbach A,Müller-Calleja N,Ritter S,Häuser F,Canisius A,Orning C,Jurk K,Lackner KJdoi
10.1055/s-0039-1685453subject
Has Abstractpub_date
2019-07-01 00:00:00pages
1147-1153issue
7eissn
0340-6245issn
2567-689Xjournal_volume
119pub_type
杂志文章abstract：:Platelet microparticles (PMPs) are small vesicles released from blood platelets upon activation. The procoagulant activity of PMPs has been previously mainly characterized by their ability to bind coagulation factors VIII and Va in reconstructed systems. It can be supposed that PMPs can contribute to the development o...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：2007-03-01 00:00:00
abstract：:Desmopressin acetate administration markedly stimulates release of tissue plasminogen activator (t-PA) from vascular endothelial cells. The mechanism for this effect is unknown. Because infusion of epinephrine has been shown to increase t-PA levels, we examined the role of endogenous catecholamine mediation of t-PA re...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1988-04-08 00:00:00
abstract：:Enhanced adhesion of sickle erythrocytes to the vascular endothelium and subendothelial matrix is fundamental to the development of vascular occlusion in sickle cell disease. Erythrocyte membrane sulfatide is implicated in the pathogenesis of vasoocclusive crises in sickle cell disease (SCD) patients. Because previous...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH10-11-0716
更新日期：2011-06-01 00:00:00
abstract：:The structures of bovine and human vWF were compared by proteolysis with Staphylococcus aureus V8 protease and rattlesnake venom Protease I. Fragments were analyzed for chain composition, heparin binding, collagen binding, platelet agglutinating activity and recognition by a panel of monoclonal antibodies which reacte...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1990-06-28 00:00:00
abstract：:Sixty-four Chinese women were studied for the effects of injecting once-a-month contraceptive norethisterone enanthate/estradiol valerate between 2 to 4 1/2 years on certain coagulation and fibrinolytic parameters, and 59 women not receiving any steroidal contraception were controls. In both groups there was no signif...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1990-12-28 00:00:00
abstract：:Protein Z-dependent protease inhibitor (ZPI) is plasma proteinase inhibitor in the serpin superfamily that produces rapid inhibition of factor Xa in the presence of phospholipids, Ca++ and protein Z (PZ). Mouse ZPI cDNA was isolated and cloned from mouse liver RNA using RT-PCR. The cDNA contains 100 nucleotides 5' of ...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：2001-05-01 00:00:00
abstract：: ...
journal_title：Thrombosis and haemostasis
pub_type： 社论
doi：10.1055/s-0038-1676073
更新日期：2018-12-01 00:00:00
abstract：:Helicobacter pylori (H. pylori) infection is associated with peptic ulcer disease and gastric cancer. The eradication of H. pylori is of special interest in patients with congenital bleeding disorders, for whom treatment of gastrointestinal hemorrhage with factor concentrates is costly. The prevalence of H. pylori var...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：2003-04-01 00:00:00
abstract：:Monospecific antisera against the purified protein component of tissue thromboplastin (apoprotein-III) from human brain have been raised in goats and rabbits. The antisera neutralized tissue thromboplastin prepared from brain, thyroid gland and pulmonary tissue, indicating that apoproteins in the various preparations ...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1977-02-28 00:00:00
abstract：:The effects of etamsylate on human platelet aggregation and ATP release as well as on the arachidonate metabolism by the platelet have been studied. Etamsylate enhanced these platelet functions induced by arachidonic acid (AA), thromboxane A2, collagen and calcium ionophore A23187 but not those induced by ADP and epin...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1982-12-27 00:00:00
abstract：:A new immunoadsorbent-amidolytic assay (IAA) for the specific differential detection of two-chain urokinase-type plasminogen activator (tcu-PA) and its single-chain precursor (scu-PA) in cell culture supernatants has been developed. The assay combines the selectivity of immunoassays with the specificity of enzyme acti...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1986-12-15 00:00:00
abstract：:We have developed a sensitive and quantitative RT-PCR assay for the determination of tissue factor (TF) mRNA levels in human cells. An in vitro synthesized internal standard RNA was used to correct for differences in reverse transcription or amplification of various RNA samples. The PCR products were quantitated by hy...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1994-02-01 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：:The contribution of the various components of the contact system in the generation of factor XIIa (FXIIa) and of kallikrein (KRN) on an electronegative surface and the release of the generated enzymes to the bulk phase was examined in mixtures of normal human plasma and plasmas congenitally deficient in these componen...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1999-09-01 00:00:00
abstract：:Binding of the coagulation protease factor VIIa to its receptor Tissue Factor (TF) induces intracellular signals in several cell types including HaCaT keratinocytes. TF belongs to the cytokine receptor family, but is most likely not alone in transferring the complete TF/FVIIa signal over the plasma membrane. The prote...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH03-08-0549
更新日期：2004-07-01 00:00:00
abstract：:The stimulated release of von Willebrand factor (vWF) from endothelial cells by secretagogues such as thrombin is associated with the translocation of Weibel-Palade bodies to the cell membrane and the surface expression of P-selectin (also known as GMP 140, PADGEM and CD 62). P-selectin, which is stored in Weibel-Pala...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1993-08-02 00:00:00
abstract：:Seven mouse monoclonal antibodies have been produced against human melanoma tissue plasminogen activator (t-PA). They were specifically bound to 125I t-PA but not 125I urokinase (u-PA) and inhibited t-PA, but not u-PA, activity in plasminogen-rich 125I fibrin wells. Three of the antibodies directly inhibited the amido...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1985-02-18 00:00:00
abstract：:Myocardial infarction in the young provides a unique model for the investigation of potential interactions between atherosclerotic and prothrombotic risk factors. Because myocardial infarction reflects atherothrombotic disease, it is important to take into account factors related to atherosclerosis when examining prot...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章,评审
doi：
更新日期：1997-07-01 00:00:00
abstract：:In 70-80% of cases, pulmonary embolism is the consequence of lower extremity deep vein thrombosis. It has been demonstrated that the most common coagulation defect predisposing to venous thrombosis, resistance to activated protein C (APC), is not associated with an increased risk for pulmonary embolism, but the eviden...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1997-03-01 00:00:00
abstract：:We studied the role of various markers of lipid metabolism, hemostasis and inflammation in a two year follow-up of 3,000 patients with angina pectoris, during which time 106 patients experienced myocardial infarction or sudden coronary death. Low levels of high density lipoprotein (HDL) cholesterol and of apolipoprote...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章,多中心研究
doi：
更新日期：2000-12-01 00:00:00
abstract：:Syndecan-4 (ryudocan) is a cell-surface heparan sulfate proteoglycan, which plays an important role in a variety of biological functions including regulation of blood coagulation. cell adhesion, and cell growth. In this study, we measured plasma levels of syndecan-4 in patients with acute myocardial infarction using a...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：2001-05-01 00:00:00
abstract：:Soluble intercellular adhesion molecule-1 (sICAM-1) and vascular cellular adhesion molecule-1 (sVCAM-1) were measured alongside flow-mediated vasodilation (FMD) in 34 patients with intermittent claudication and 14 control subjects. Patients with plasma sICAM-1 >253 ng/mL (median value) showed lower FMD than those with...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：2001-01-01 00:00:00
abstract：:Studies examining the interaction of platelets with exposed subendothelium in vivo have reported conflicting results. To examine possible explanations for the apparently discrepant findings, we measured the platelet reactivity of subendothelium prepared by a number of methods both in vivo and in vitro. In addition, we...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1987-08-04 00:00:00
abstract：:Pulmonary arterial hypertension (PAH) is characterised by increased pressure in the pulmonary arteries leading to right-sided ventricular failure, and death. Identification of factors that affect patient survival is important to improve patient management and outcomes. The first registry to evaluate survival and devel...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章,评审
doi：10.1160/TH11-11-0821
更新日期：2012-12-01 00:00:00
abstract：:Although it is recognized that glycoprotein (GP) IIb-IIIa complexes are deficient in platelets in Glanzmann's thrombasthenia, little is known of the origin of the defect. We have examined the megakaryocytes in a bone marrow aspirate obtained from a thrombasthenia patient during surgery. Analysis of platelet proteins b...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1986-08-20 00:00:00
abstract：:Clopidogrel is a recently introduced platelet ADP receptor antagonist, belonging to the thienopyridine derivatives, like its analogue ticlopidine. Its potential advantage is to be safer than ticlopidine. At 75 mg/od clopidogrel significantly inhibits platelet aggregation in ambulatory patients with symptomatic atheros...
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：1999-11-01 00:00:00
abstract：:Mature circulating endothelial cells (CECs) are novel cellular markers of endothelial damage/dysfunction. The two main techniques of CEC enumeration are flow cytometry (FC) and immunomagnetic bead (IB) isolation. Both quantify CECs accurately, but a direct comparison of both methods has not been reported. We sought to...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH06-04-0185
更新日期：2006-07-01 00:00:00
abstract：:In the last decade, the endothelial cell protein C/activated protein C receptor (EPCR) has received considerable attention. The role initially attributed to EPCR, i.e. the enhancement of protein C (PC) activation by the thrombin-thrombomodulin complex on the surface of the large vessels, although important, did not go...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章,评审
doi：10.1160/TH11-11-0766
更新日期：2012-05-01 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：BACKGROUND:Platelet activation plays a major role in acute vessel closure after coronary angioplasty. In the randomized Balloon Angioplasty and Anticoagulation Study (BAAS), pretreatment with oral anticoagulants in addition to aspirin resulted in a 47% reduction of acute complications as compared with aspirin alone. Th...
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：2002-12-01 00:00:00
