Abstract:
:Bacterial pneumonia, the most common cause of sepsis, is associated with activation of coagulation. Factor XI (FXI), the key component of the intrinsic pathway, can be activated via factor XII (FXII), part of the contact system, or via thrombin. To determine whether intrinsic coagulation is involved in host defence during pneumonia and whether this is dependent on FXII activation, we infected in parallel wild-type (WT), FXI knockout (KO) and FXII KO mice with two different clinically relevant pathogens, the Gram-positive bacterium Streptococcus pneumoniae and the Gram-negative bacterium Klebsiella pneumoniae, via the airways. FXI deficiency worsened survival and enhanced bacterial outgrowth in both pneumonia models. This was accompanied with enhanced inflammatory responses in FXI KO mice. FXII KO mice were comparable with WT mice in Streptococcus pneumoniae pneumonia. On the contrary, FXII deficiency improved survival and reduced bacterial outgrowth following infection with Klebsiella pneumoniae. In both pneumonia models, local coagulation was not impaired in either FXI KO or FXII KO mice. The capacity to phagocytose bacteria was impaired in FXI KO neutrophils and in human neutrophils where activation of FXI was inhibited. Deficiency for FXII or blocking activation of FXI via FXIIa had no effect on phagocytosis. Taken together, these data suggest that FXI protects against sepsis derived from Streptococcus pneumoniae or Klebsiella pneumoniae pneumonia at least in part by enhancing the phagocytic capacity of neutrophils by a mechanism that is independent of activation via FXIIa.
journal_name
Thromb Haemostjournal_title
Thrombosis and haemostasisauthors
Stroo I,Zeerleder S,Ding C,Luken BM,Roelofs JJTH,de Boer OJ,Meijers JCM,Castellino FJ,van 't Veer C,van der Poll Tdoi
10.1160/TH16-12-0920subject
Has Abstractpub_date
2017-07-26 00:00:00pages
1601-1614issue
8eissn
0340-6245issn
2567-689Xpii
16-12-0920journal_volume
117pub_type
杂志文章abstract::The aim of the present study was to evaluate the relative performance of five screening methods for APC resistance caused by the factor V:Q506 mutation: the original method Coatest APC Resistance Chromogenix, a modified method using the same reagents but a predilution 1+4 of the plasma in a factor V deficient plasma f...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1997-11-01 00:00:00
abstract::We studied a murine monoclonal antibody (211 A6) to von Willebrand factor (vWF) with a view to investigating structure-relationship of plasma vWF. The specificity of this antibody has been substantiated by ELISA tests and indirect immunofluorescence. It reacts with purified vWF, normal plasma but not with plasma or pl...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1987-06-03 00:00:00
abstract::It was the study objective to evaluate whether chewing a 180 mg loading dose of ticagrelor versus an equal dose of traditional oral administration, enhances inhibition of platelet aggregation 1 hour (h) after administering a ticagrelor loading dose in non-ST elevation myocardial infarction (NSTEMI) patients. Dual anti...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,随机对照试验
doi:10.1160/TH16-09-0728
更新日期:2017-04-03 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 prevention and treatment of venous thromboembolism (VTE) remains a clinical challenge, primarily owing to drawbacks associated with the use of heparins and vitamin K antagonists (VKAs). These and other factors, including a growing elderly population, mean that VTE presents a continuing burden to patients and physi...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,meta分析,评审
doi:10.1160/TH14-06-0484
更新日期:2015-02-01 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::We investigated the protective effects of DX-9065a, an orally active, newly synthesized and specific inhibitor of factor Xa, against two kinds of experimental disseminated intravascular coagulation (DIC) in rats. Endotoxin-induced experimental DIC was induced by a 4-h sustained infusion of endotoxin at a dose of 100 m...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1994-09-01 00:00:00
abstract::The generation of D-dimer was studied in the course of local thrombolytic therapy of peripheral arterial occlusions with low doses of recombinant human tissue-type plasminogen activator (rt-PA) in 7 patients. Intermittent local application of rt-PA resulted in a marked increase in D-dimer exceeding values usually seen...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1990-10-22 00:00:00
abstract::Recombinant factor VIIa (rFVIIa; Novoseven) is used for treatment of hemophilia patients with inhibitors. There are poorly defined differences in clinical responsiveness between individuals. Prior to licensure in the United States, rFVIIa was available through the compassionate use program, during which two patients d...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:2002-07-01 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:2001-08-01 00:00:00
abstract::Patients with both chronic kidney disease (CKD) and diabetes mellitus (DM) are at increased risk for thrombotic events compared to those with one abnormality alone. Whether this can be attributed to changes in platelet reactivity among those with both CKD and DM is unknown. We prospectively studied 438 clopidogrel-naï...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH13-01-0004
更新日期:2013-07-01 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::Hemolytic uremic syndrome (HUS), the leading cause of acute renal failure in children (< 3 years), is mainly related to Shiga toxins (Stx)-producing Escherichia coli (STEC) infections. STEC are confined to the gut resulting in hemorrhagic colitis, whereas Stx are delivered in blood to target kidney and brain, with unc...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1055/s-0039-3400301
更新日期:2020-01-01 00:00:00
abstract::Alpha-enolase is an ubiquitous cytoplasmic glycolytic enzyme which also exhibits cell surface mediated functions and a structural role in the lens of some species. An alpha-enolase related molecule (alpha-ERM) is present on the surfaces of neutrophils, monocytes and monocytoid cells and has the capacity to specificall...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1997-09-01 00:00:00
abstract::The carboxy-terminal region of hirudin (residues 54-65) has previously been shown to inhibit thrombin clotting activity without binding to the catalytic site of the enzyme. In the present study, the effect of hirudin 54-65 on thrombin interaction with specified platelet proteins has been investigated. Hirudin 54-65 wa...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1991-09-02 00:00:00
abstract::Previously, we demonstrated in a rat model of heparin-induced osteoporosis that low molecular weight heparin (LMWH) produces less bone loss than unfractionated heparin, and that only heparin increases osteoclast number and activity. In contrast, both heparin and LMWH were found to decrease osteoblast function to a sim...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1998-09-01 00:00:00
abstract::Plasma samples from 35 patients with colorectal cancer, 16 patients with pancreatic cancer and 46 patients with various cancers in the terminal stage were analysed for soluble plasma thrombomodulin with an ELISA method. At time of diagnosis and before primary treatment, the patients with colorectal cancer had normal p...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1993-02-01 00:00:00
abstract::The methylenetetrahydrofolate reductase (MTHFR) 677 C→T polymorphism may be associated with elevated total homocysteine (tHcy) levels, an independent risk factor for cardiovascular disease. It was the study objective to evaluate in vivo lipid peroxidation and platelet activation in carriers of the MTHFR 677 C→T polymo...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH11-12-0899
更新日期:2012-09-01 00:00:00
abstract:: ...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1055/s-0038-1657075
更新日期:1979-07-01 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1984-12-29 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH12-12-0898
更新日期:2013-08-01 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1991-11-01 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1984-02-28 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH14-01-0024
更新日期:2014-10-01 00:00:00
abstract::Using an in vitro model of clot lysis, the individual response to a pharmacological concentration of recombinant tissue plasminogen activator (rt-PA) and the influence on this response of the physiological variations of blood parameters known to interfere with the fibrinolytic/thrombolytic process were investigated in...
journal_title:Thrombosis and haemostasis
pub_type: 临床试验,杂志文章
doi:
更新日期:1997-04-01 00:00:00
abstract::Platelet membrane glycoproteins (GP) IIb/IIa and rap1b, a 21 kDa GTP binding protein, associate with the triton-insoluble, activation-dependent platelet cytoskeleton with similar rates and divalent cation requirement. To examine the possibility that GPIIb/IIIa was required for rap1b association with the cytoskeleton, ...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1998-04-01 00:00:00
abstract::Accumulating evidence suggests an immune-modulatory role for platelets (PLT) and PLT-derived microvesicles. In particular, ectosomes, i.e. vesicles budding from PLT surface, have been shown to exert immunosuppressive activities on phagocytes. Here we investigated the effects mediated by PLT-derived ectosomes (PLT-Ecto...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH14-03-0281
更新日期:2014-12-01 00:00:00
abstract::To evaluate the role of low-molecular weight heparin (LMWH) as an alternative to oral anticoagulants in the prevention of recurrent venous thromboembolism, we compared in a randomized trial conventional warfarin treatment with a three-month course of enoxaparin 4000 anti-Xa units once a day subcutaneously. 187 patient...
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:1994-08-01 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,多中心研究
doi:10.1160/TH11-04-0208
更新日期:2011-08-01 00:00:00
abstract::Charge-to-alanine mutations of three amino acid residues, viz, D46, D48, and D/Hya71, which are known to be important in stabilizing Ca2+ binding to epidermal growth factor (EGF) domains of vitamin K-dependent blood coagulation proteins, have been engineered into recombinant human protein C (r-PC). The resulting varia...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1996-11-01 00:00:00