Tissue factor de-encryption, thrombus formation, and thiol-disulfide exchange.


:Tissue factor (TF) by forming a complex with factor VIIa (FVIIa) initiates blood coagulation. It was traditionally believed that the separation of FVIIa in circulation from subendothelial TF was the main control that was preventing spontaneous initiation of thrombosis and that circulating cells and endothelium did not express TF protein at rest in healthy individuals. However, TF has been detected in healthy human plasma and animal models of thrombosis, which indicate that TF in circulation can contribute to thrombin generation and fibrin formation after an activation event. Circulating TF-and indeed, most of the TF on the cell surface-is "encrypted" or coagulation inactive. The de-encryption step involves exposure of phosphatidylserine (PS), but PS exposure alone is insufficient for full TF activity. Allosteric disulfide bonds control protein function by mediating conformal change through the formation and breaking of disulfide bonds. TF contains a typical surface exposed allosteric bond in the membrane proximal fibronectin type III domain. Thiol-disulfide exchange involving this disulfide is implicated in TF activation with the formation of the disulfide bond corresponding with the active conformation of TF and free thiol or thiol-modified forms corresponding with encryption. Although the exact mechanism by which TF de-encryption occurs remains a subject of debate, thiol blockade and inhibition of oxidoreductases show an important role for thiol-disulfide reactions in platelet-independent pathways of coagulation in vitro and in vivo. In particular, redox active extracellular protein disulfide isomerase is involved in the earliest stages of thrombus initiation and has proven to be a potential target for antithrombotic drug development.


Semin Thromb Hemost


Chen VM




Has Abstract


2013-02-01 00:00:00












  • Aspects of the laboratory identification of von Willebrand disease in women.

    abstract::The increased prevalence of the laboratory diagnosis of von Willebrand disease (vWD) in women presenting with menorrhagia has raised concerns regarding certain specifics in vWD testing in women, including when vWD testing should be done in relation to menses and whether testing should be done while the patient is not ...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章,评审


    authors: Kouides PA

    更新日期:2006-07-01 00:00:00

  • Active online assessment of patients using new oral anticoagulants: bleeding risk, compliance, and coagulation analysis.

    abstract::Clinicians prescribing new oral anticoagulants (OACs; dabigatran, rivaroxaban, and apixaban) should be aware of the exclusion criteria related to bleeding risks defined in published clinical studies. At least a quarter of patients currently using warfarin have an exclusion criterion that may prevent easy transition to...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章,评审


    authors: Salmela B,Joutsi-Korhonen L,Armstrong E,Lassila R

    更新日期:2012-02-01 00:00:00

  • Anti-factor H autoantibody-associated hemolytic uremic syndrome: review of literature of the autoimmune form of HUS.

    abstract::Non-Shiga toxin-associated hemolytic uremic syndrome (atypical HUS) is a rare form of thrombotic microangiopathy that associates hemolytic anemia, thrombocytopenia, and acute renal failure. The disease has been demonstrated to be linked with a complement alternative pathway dysregulation due to genetic defects but als...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章,评审


    authors: Dragon-Durey MA,Blanc C,Garnier A,Hofer J,Sethi SK,Zimmerhackl LB

    更新日期:2010-09-01 00:00:00

  • Comparative in vitro investigation of prothrombin complex concentrates.

    abstract::Three commercial prothrombin complex concentrates (PCC) were compared in vitro. Differences in the activities or contents, respectively, of the PCC factors FII, FVII, FIX, FX and the proteins C, S, and Z (antigen) in particular were found. Global tests of activated factors did not reveal marked differences between the...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章


    authors: Römisch J,Bonik K,Müller HG

    更新日期:1998-01-01 00:00:00

  • A consensus approach to the formulation of guidelines for laboratory testing and reporting of antiphospholipid antibody assays.

    abstract::Despite numerous past and ongoing efforts, there remains significant variation in results from assays for the major antiphospholipid antibodies (aPL), namely anticardiolipin (aCL), anti-beta2 glycoprotein I (anti-beta2GPI), and lupus anticoagulant (LA). There is therefore a need to produce comprehensive guidelines on ...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章,评审


    authors: Wong RC,Favaloro EJ

    更新日期:2008-06-01 00:00:00

  • Outcome of Major Hemorrhage at a Major Cardiothoracic Center in Patients with Activated Major Hemorrhage Protocol versus Nonactivated Protocol.

    abstract::This study aimed to determine the impact of major hemorrhage (MH) protocol (MHP) activation on blood administration and patient outcome at a UK major cardiothoracic center. MH was defined in patients (> 16 years) as those who received > 5 units of red blood cells (RBCs) in < 4 hours, or > 10 units in 24 hours. Data we...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章


    authors: Chang KW,Owen S,Gaspar M,Laffan M,Arachchillage DRJ

    更新日期:2021-02-01 00:00:00

  • Factor v Leiden mutation in severe infection and sepsis.

    abstract::In severe infection and sepsis, activation of coagulation frequently occurs, which contributes to the development of multiple organ dysfunction. Factor V Leiden is a relatively common mutation resulting in a mild prohemostatic state and consequently with an increased tendency to develop thrombosis. Hypothetically, pat...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章,评审


    authors: Levi M,Schouten M,van't Veer C,van der Poll T

    更新日期:2011-11-01 00:00:00

  • Acute pulmonary embolism after an earthquake in Japan.

    abstract::There have been no reports on acute pulmonary embolism (APE) after earthquakes. Our aim was to clarify the actual the occurrence of APE following the 2004 Mid Niigata Prefecture earthquake in Japan, and to assess the risk factors for APE after the event. We sent questionnaires to 122 hospitals in the Niigata Prefectur...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章,多中心研究


    authors: Sakuma M,Nakamura M,Hanzawa K,Kobayashi T,Kuroiwa M,Nakanishi N,Miyahara Y,Tanabe N,Yamada N,Kuriyama T,Kunieda T,Sugimoto T,Nakano T,Shirato K

    更新日期:2006-11-01 00:00:00

  • Inhibitors in hemophilia A: advances in elucidation of inhibitory mechanisms and in inhibitor management with bypassing agents.

    abstract::Development of inhibitory antibodies (inhibitors) to factor VIII (FVIII) is the most serious adverse event in replacement therapy of hemophilia A patients. The etiology and management of this condition remain major challenges for both researchers and clinicians. In the present review, we discuss recent advances in und...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章,评审


    authors: Ananyeva NM,Lee TK,Jain N,Shima M,Saenko EL

    更新日期:2009-11-01 00:00:00

  • Alpha-thrombin stimulates expression of macrophage migration inhibitory factor in skin fibroblasts.

    abstract::Macrophage migration inhibitory factor (MIF) is induced by various stimuli such as wounds and infection and regulates inflammatory and immunological responses. To date, we have found increased expression of MIF during the wound healing process in rat skin. Immunohistochemical analysis demonstrated enhanced expression ...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章


    authors: Shimizu T,Ohkawara A,Mizue Y,Nishihira J

    更新日期:1999-01-01 00:00:00

  • Factor XIII in chronic inflammatory bowel diseases.

    abstract::Severe acute inflammation in chronic inflammatory bowel disease is associated with large wound areas and ulcerations that show spontaneous hemorrhage or marked friability. Therefore, an enormous potential of hemostasis and wound healing is required. Coagulation studies demonstrate a deficiency of factor XIII that is i...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章,评审


    authors: Lorenz R,Olbert P,Born P

    更新日期:1996-01-01 00:00:00

  • Structure and function studies of factor XIIIa by x-ray crystallography.

    abstract::The three-dimensional structures of several forms of the factor XIII A subunit have been determined using single crystal x-ray diffraction methods. Our crystallographic studies have provided the first detailed structural view of the factor XIII A subunit and information that is useful for understanding transglutaminas...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章


    authors: Yee VC,Le Trong I,Bishop PD,Pedersen LC,Stenkamp RE,Teller DC

    更新日期:1996-01-01 00:00:00

  • Development and performance characteristics of a competitive enzyme immunoassay for fibrinopeptide A.

    abstract::A simple nonisotopic method for the quantitation of FPA in biologic samples has been developed utilizing a competitive enzyme immunoassay technique. The performance characteristics of these assays have been investigated in both the experimental and clinical settings and were found to be satisfactory for the routine cl...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章


    authors: Amiral J,Walenga JM,Fareed J

    更新日期:1984-10-01 00:00:00

  • Thrombosis and thrombophilia in children: a systematic review.

    abstract::Thrombotic events are uncommon disorders in childhood but increasingly recognized due to the progress made in the understanding of the hemostasis system and the importance of thromboembolic disorders in children. Multiple clinical underlying conditions and prothrombotic disorders contribute to the development of throm...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章,评审


    authors: Tormene D,Gavasso S,Rossetto V,Simioni P

    更新日期:2006-10-01 00:00:00

  • Treatment options for clinically recognized disseminated intravascular coagulation.

    abstract::Current concepts of etiology and pathophysiology resulting in disseminated intravascular coagulation (DIC) form the basis of treatment of this hemostatic disorder. Due to the heterogeneous triggering diseases and different kinds of DIC, clinical symptoms such as predominant bleeding, thromboembolic complications or or...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章,评审


    authors: Riewald M,Riess H

    更新日期:1998-01-01 00:00:00

  • The putative mechanism of thrombosis in antiphospholipid syndrome: impairment of the protein C and the fibrinolytic systems by monoclonal anticardiolipin antibodies.

    abstract::The mechanism of thrombosis in patients with antiphospholipid syndrome is not clear. To investigate it, we examined the effect of monoclonal anticardiolipin (aCL) antibodies and beta2-glycoprotein I (beta2-GPI), which is required for formation of the aCL epitopes, on activated protein C (APC) and on fibrinolytic activ...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章,评审


    authors: Ieko M,Sawada KI,Koike T,Notoya A,Mukai M,Kohno M,Wada N,Itoh T,Yoshioka N

    更新日期:1999-01-01 00:00:00

  • Angiostatin.

    abstract::The quiescent vascular system in the adult body represents the imbalanced net outcome of overproduction of endogenous angiogenesis inhibitors and reduced levels of angiogenic factors. While some endogenous inhibitors are expressed under physiological conditions, they can also be generated in association with tumor gro...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章,评审


    authors: Cao Y,Xue L

    更新日期:2004-02-01 00:00:00

  • Diagnosis of venous thromboembolism in children.

    abstract::Venous thromboembolic events (VTE) in children are mostly related to central venous lines (CVL), and are located in the central upper venous system. The incidence of VTE in children with CVL is significant. However, the majority of CVL-related VTE do not present with typical symptoms or are not recognized due to under...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章,评审


    authors: Male C,Kuhle S,Mitchell L

    更新日期:2003-08-01 00:00:00

  • Strategy for the development of the low molecular weight heparin fraction CY 216 in the prevention of postoperative deep vein thromboses in general surgery.

    abstract::The polymorphism in the composition and actions of heparin and the parallel complexity of the thrombotic process have led to the design of a cautious, methodical, and pragmatic program of development of the first low molecular heparin fraction presently available in France (CY 216). The main idea was always to present...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 临床试验,历史文章,杂志文章,随机对照试验


    authors: Toulemonde F

    更新日期:1989-10-01 00:00:00

  • Treatment of polycythemia vera.

    abstract::The selection of treatment for patients with polycythemia vera (PV) still is the subject of much discussion among hematologists. It is emphasized that important physiologic and pathogenic components of the illness relate not only to the erythroid cell, but also to the megakaryocyte. Both play essential roles in causin...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章,评审


    authors: Silver RT

    更新日期:2006-06-01 00:00:00

  • Tissue factor pathway inhibitor (TFPI) antigen plasma level in patients with interstitial lung disease before and after heparin administration.

    abstract::The extrinsic pathway is probably the predominant pathway in initiating blood coagulation in inflammatory lung diseases. Tissue factor pathway inhibitor (TFPI) is a Kunitz-type protease inhibitor of factor VIIa/tissue factor in the presence of factor Xa. As it has been shown recently that TFPI plasma levels are increa...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章


    authors: Cella G,Cipriani A,Tommasini A,Rampin E,Sbarai A,Rocconi R,Mazzaro G,Luzzatto G

    更新日期:1997-01-01 00:00:00

  • Experimental and clinical validation of the prophylactic antithrombotic effects of a low molecular weight heparin (enoxaparin).

    abstract::Several LMWHs are currently available for commercial use. The development status of each of these products in the area of prophylaxis, therapeutics, and other indications is given in Table 4. Enoxaparin and Fraxiparin appear to be the most developed LMWHs in both the surgical and medical areas. Many well-designed clin...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章,评审


    authors: Fareed J,Walenga JM,Hoppensteadt D,Borris LC,Lassen MR

    更新日期:1991-01-01 00:00:00

  • Molecular mechanisms of megakaryocyte differentiation.

    abstract::Each bone marrow megakaryocyte (MK) releases thousands of platelets into the circulation, and the underlying molecular and cellular mechanisms recently have received intense scrutiny. Genetic studies are beginning to clarify the mechanisms by which transcription factors help distinguish MK progenitors from other blood...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章,评审


    authors: Schulze H,Shivdasani RA

    更新日期:2004-08-01 00:00:00

  • Diagnosis and management of von Willebrand disease in The Netherlands.

    abstract::In the Netherlands, specialized care for patients with a bleeding disorder, including hemophilia, von Willebrand disease (VWD), and allied disorders, is concentrated in 13 Hemophilia Treatment Centers. The Dutch Hemophilia Treaters Society, the Dutch Hemophilia Nurses' Society, and the Netherlands Hemophilia Patients ...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章,评审


    authors: de Wee EM,Leebeek FW,Eikenboom JC

    更新日期:2011-07-01 00:00:00

  • Shear-, Sound-, and Light-Sensitive Nanoparticles for Thrombolytic Drug Delivery.

    abstract::Thrombotic diseases, as potentially induced by blood clots or vascular embolization, frequently occur with high rates of mortalities worldwide. Current drug thrombolysis, a primary clinical therapy, may increase fatal risk of hemorrhage when thrombolysis agents become systemically distributed. Given current thrombolys...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章


    authors: Qu S,Ding X

    更新日期:2020-07-01 00:00:00

  • The P2 receptors and congenital platelet function defects.

    abstract::Platelets possess three P2 receptors: two (P2Y (1) and P2Y (12)) are receptors for adenosine diphosphate (ADP), and one (P2X1) is a receptor for adenosine triphosphate (ATP). The P2Y (1) receptor, which is coupled to Gq and phospholipase C-beta, is responsible for mobilization of ionized calcium from internal stores a...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章,评审


    authors: Cattaneo M

    更新日期:2005-04-01 00:00:00

  • Evaluation of hematologic alterations associated with daily administration of low molecular weight heparin (Mono-Embolex) for a 12-week period.

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    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章


    authors: Lojewski B,Bacher P,Iqbal O,Walenga JM,Hoppensteadt DA,Leya F,Fareed J

    更新日期:1993-01-01 00:00:00

  • Inhibition of platelet function: does it offer a chance of better cancer progression control?

    abstract::Thrombocytosis is frequently (10 to 57%) observed in cancer patients. Although the mechanisms underlying thrombocytosis are not yet fully elucidated, tumor-derived factors with thrombopoietin-like activity, growth factors, platelet-derived microparticles, and factors released from bone marrow endothelial cells as well...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章,评审


    authors: Sierko E,Wojtukiewicz MZ

    更新日期:2007-10-01 00:00:00

  • Use of D-dimer assays in the diagnosis of venous thrombosis.

    abstract::In the course of fibrin formation, the D-domains of adjacent fibrin molecules within the fibrin polymer are covalently linked by factor XIIIa, leading to the formation of a D-domain dimer. Proteolysis of this cross-linked fibrin generates fibrin fragments D-dimer and E as terminal products. Fragment D-dimer therefore ...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章,评审


    authors: Dempfle CE

    更新日期:2000-01-01 00:00:00

  • Metabolic modulation of inflammation-induced activation of coagulation.

    abstract::The bidirectional interaction between coagulation and inflammation, which is relevant in various disease states that are dominated by systemic inflammatory responses, such as severe infection or chronic vascular disease, is modulated by metabolic factors. Changes in lipoprotein metabolism affect the inflammation-induc...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章,评审


    authors: Levi M,Nieuwdorp M,van der Poll T,Stroes E

    更新日期:2008-02-01 00:00:00