Seminars in Thrombosis and Hemostasis

Publisher: Georg Thieme Verlag

Journal description

Current impact factor: 3.88

Impact Factor Rankings

2015 Impact Factor Available summer 2016
2014 Impact Factor 3.876
2013 Impact Factor 3.693
2012 Impact Factor 4.216
2011 Impact Factor 4.524
2010 Impact Factor 4.169
2009 Impact Factor 3.214
2008 Impact Factor 3.695
2007 Impact Factor 3.202
2006 Impact Factor 2.733
2005 Impact Factor 2.077
2004 Impact Factor 2.018
2003 Impact Factor 1.906
2002 Impact Factor 2.497
2001 Impact Factor 2.147
2000 Impact Factor 2.179
1999 Impact Factor 2.385
1998 Impact Factor 1.577
1997 Impact Factor 1.171
1996 Impact Factor 1.15
1995 Impact Factor 1.175
1994 Impact Factor 1.483
1993 Impact Factor 1.415
1992 Impact Factor 1.542

Impact factor over time

Impact factor

Additional details

5-year impact 3.57
Cited half-life 5.70
Immediacy index 2.32
Eigenfactor 0.01
Article influence 0.97
ISSN 1098-9064
OCLC 163849709
Material type Internet resource
Document type Internet Resource, Computer File, Journal / Magazine / Newspaper

Publisher details

Georg Thieme Verlag

  • Pre-print
    • Author cannot archive a pre-print version
  • Post-print
    • Author can archive a post-print version
  • Conditions
    • Author's post-print or Publisher's version/PDF on author's personal website immediately
    • Author's post-print in Institutional Repository and PubMed Central after 12 months embargo
    • Publisher's version/PDF can be used on author's personal website only
    • Publisher copyright and source must be acknowledged
    • Link to Publisher version ( must be included if article has been published online
    • Publisher last contacted on 31/03/2015
    • 'Georg Thieme Verlag' is an imprint of 'Thieme Publishing'
  • Classification
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Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: Tissue factor (TF) is a 47-kDa transmembrane glycoprotein and the main initiator of the blood coagulation cascade. Binding to its ligand factor VIIa (FVIIa) also initiates noncoagulant signaling with broad biological implications. In this review, we discuss how TF interacts with other cell-surface proteins, which affect biological functions such as cell migration and cell survival. A vast number of publications have demonstrated the importance of TF-induced activation of protease-activated receptors, but recently published research has indicated a more complicated picture. As it has been discovered that TF interacts with integrins and receptor tyrosine kinases, novel signaling mechanisms for the TF/FVIIa complex have been presented. The knowledge of these new aspects of TF signaling may, for instance, facilitate the development of new treatment strategies for cancer and acute coronary syndromes, two examples of diseases characterized by aberrant TF expression and signaling.
    Seminars in Thrombosis and Hemostasis 09/2015; DOI:10.1055/s-0035-1564046
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    ABSTRACT: Introduction Limited information exists on gender-related differences in the safety and efficacy of non-vitamin K antagonist oral anticoagulants (NOACs). Aim of the Study To assess the safety and efficacy of direct oral anticoagulants (DOACs)/NOACs in men and women pooling data from randomized controlled trials on the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation (AF) and on the acute and extended treatment of venous thromboembolism (VTE). Methods MEDLINE and EMBASE databases were searched up to June 2014. The efficacy outcome was defined as the prevention of stroke and systemic embolism (AF studies), or as the prevention of recurrent VTE or VTE-related death (VTE studies). The safety outcome was defined as the occurrence of major and/or clinically relevant nonmajor bleeding. Differences in the efficacy and safety outcomes were expressed as risk ratio (RR) with pertinent 95% confidence intervals (95% CI). Results A total of 13 studies (> 100,000 patients) were included. DOACs appeared to have a similar efficacy and safety compared with vitamin K antagonists in female and male patients treated for nonvalvular AF and acute VTE. In the extended treatment of VTE NOACs had a RR of bleeding of 4.97 (95% CI 1.06, 23.41) in males and 1.33 (95% CI 0.63, 2.83) in females compared with placebo (subgroup difference chi-square test: 2.25, p = 0.13). Conclusions No gender-related difference in the efficacy and safety of NOACs in patients with AF or acute VTE was found. A trend toward an increased risk of bleeding in male patients as compared with female patients was detected in the extended treatment of VTE.
    Seminars in Thrombosis and Hemostasis 09/2015; DOI:10.1055/s-0035-1564042
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    ABSTRACT: The contribution of vessel wall-derived tissue factor (TF) to atherothrombosis is well established, whereas the pathophysiological relevance of the blood-borne TF is still a matter of debate, and controversies on the presence of platelet-associated TF still exist. In the past 15 years, several studies have documented the presence of TF in human platelets, the capacity of human platelets to use TF mRNA to make de novo protein synthesis, and the increase in the percentage of TF positive platelets in pathological conditions such as coronary artery disease (CAD). The exposure of vessel wall-derived TF at the site of vascular injury would play its main role in the initiation phase, whereas the blood-borne TF carried by platelets would be involved in the propagation phase of thrombus formation. More recent data indicate that megakaryocytes are committed to release into the bloodstream a well-defined number of TF-carrying platelets, which represents only a fraction of the whole platelet population. These findings are in line with the evidence that platelets are heterogeneous in their functions and only a subset of them is involved in the hemostatic process. In this review we summarize the existing knowledge on platelet associated TF and speculate on its relevance to physiology and to atherothrombosis and CAD.
    Seminars in Thrombosis and Hemostasis 09/2015; DOI:10.1055/s-0035-1564041
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    ABSTRACT: It is generally accepted that the initial event in coagulation and intravascular thrombus formation is the exposure of the flowing blood to cell-surface protein, such as tissue factor (TF). Vascular injury and/or atherosclerotic plaque complication is responsible for this exposure, leading to clinical manifestations such as acute coronary syndromes. For many years, TF has been considered one of the major determinants of plaque-related thrombosis. However, the discoveries of different pools of TF that circulates in the blood as cell-associated TF, microparticles bound, and as soluble form have changed this dogma. Recent evidence suggests that an increased circulating TF activity may potentiate the initial thrombogenic stimulus related to vessel wall-associated TF, leading to the formation of larger and/or more stable thrombus and thus more severe clinical manifestations. Different pathological conditions, such as inflammatory status, enhance TF expression and activity. Conversely, TF upregulation may facilitate inflammation by formation of proinflammatory fibrin fragments and coagulation proteases generation, including FVIIa, FXa, and thrombin. Furthermore, the biology of TF has become more complex by the demonstration that, apart from its known effects on blood coagulation, it is involved in intracellular signaling, proliferation, angiogenesis, and tumor metastasis.
    Seminars in Thrombosis and Hemostasis 09/2015; DOI:10.1055/s-0035-1564045
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    ABSTRACT: Blood coagulation is one of the most profound factors that influence cancer progression. Especially the initiator of coagulation, tissue factor (TF), has been subject to many studies investigating the overlap between coagulation and cancer. It has been known for decades that TF is a risk factor for metastasis, and in mouse models, TF drives metastasis in a coagulation-dependent manner. However, TF also serves as a cellular receptor to drive primary tumor growth and tumor angiogenesis. Nevertheless, recent studies have indicated that TF plays more fundamental roles in cancer biology. TF regulates tumor cell dormancy, is associated with cancer stem cell behavior, epithelial-to-mesenchymal transition, and dictates establishment of the tumor cell premetastatic niche. Especially with regard to these recent roles attributed to TF, no clear idea exists on the exact molecular pathways that are initiated by TF. Finally, TF alternative splicing results in an isoform with different characteristics and functions in cancer. In this review, a summary will be given on both the established as well as the new aspects of TF function in cancer progression.
    Seminars in Thrombosis and Hemostasis 09/2015; DOI:10.1055/s-0035-1556048
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    ABSTRACT: Thrombosis is a major cause of morbidity and mortality in cancer patients. Many clinical factors contribute to the high thrombotic risk of this condition, including the type of malignancy, its disease stage, anticancer therapies, and comorbidities. However, the cancer cell-specific prothrombotic properties together with the host cell inflammatory response are important players in the pathogenesis of the cancer-associated hypercoagulability. Tissue factor (TF) is the most important procoagulant protein expressed by cancer cells, and with other cancer tissue procoagulant properties highly contributes to the procoagulant phenotype of malignant cells. Recent discoveries indicate that oncogenes determine the procoagulant protein expression, including TF, in cancer tissues. In addition, in malignancy, TF is also overexpressed by host normal blood cells triggered by cancer-derived inflammatory stimuli. As a consequence, a subclinical activation of blood coagulation is typically present in cancer patients, as demonstrated by abnormalities of circulating thrombotic biomarkers. The relevance of measuring these biomarkers to determine the patient thrombotic risk level is under active investigation. The goal is to identify the high-risk subgroups to establish more accurate and targeted anticoagulation strategies to prevent thrombosis in cancer patients. Ultimately, the clarification of specific molecular mechanisms triggering blood coagulation in specific cancer types may also indicate alternative ways to inhibit clotting activation in these conditions.
    Seminars in Thrombosis and Hemostasis 09/2015; DOI:10.1055/s-0035-1564040
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    ABSTRACT: The transition from the classic role of neutrophils as the first line of defense of the immune system to that of physiological regulators of intravascular thrombosis took nearly three decades to emerge. This transition needed time to unravel the complex links between the mechanisms that regulate hemostasis and inflammation and the innate immune response, multicellular and multifactorial processes that interact with each other. The present review is focused on the expression of tissue factor by neutrophils, a critical event in their inflammatory and thrombotic function.
    Seminars in Thrombosis and Hemostasis 09/2015; DOI:10.1055/s-0035-1564043
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    ABSTRACT: In the last few years, a great improvement in the management of clinical thromboembolism has been made thanks to the availability of novel oral anticoagulants. These drugs, which act by directly inhibiting thrombin (dabigatran) or activated factor X (apixaban, rivaroxaban, and edoxaban), offer several practical advantages over the traditional vitamin K antagonists (VKA), such as a more predictable anticoagulant effect with no need for routine coagulation monitoring and a limited drug and food interaction. Several phase III clinical trials have now been completed, overall demonstrating that non-VKA oral antagonists (NOACs) are at least as efficacious and safe as VKA in the prevention and treatment of thromboembolism. Nevertheless, patients receiving NOACs represent a new challenge because no antidotes are currently available for these drugs. In this review, after a description of the main pharmacologic characteristics and the main results of the clinical trials of NOACs, we will focus on the management of bleeding associated with these anticoagulant agents. A treatment algorithm of NOACs-associated bleeding is finally provided, with the aim of helping physicians in their daily care activity.
    Seminars in Thrombosis and Hemostasis 09/2015; DOI:10.1055/s-0035-1556046
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    ABSTRACT: Microparticles (MP) are small extracellular vesicles (30-1,000 nm) that are released from activated cells or platelets. Exposure of negatively charged phospholipids and tissue factor (TF) renders MP procoagulant. Normal plasma levels of intravascular TF-exposing MP (TFMP) are low, but their number may rise in pathological conditions, including cancer and infectious disease. Emerging evidence indicates an important role for these circulating TFMP in the pathogenesis of thrombotic complications such as venous thromboembolism and disseminated intravascular coagulation, whereas their contribution to arterial thrombosis is less studied. Despite serious limitations of the currently available assays for measuring TFMP levels or the procoagulant activity associated with TFMP with respect to sensitivity and specificity, the scientific interest in TFMP is rapidly growing because their application as prognostic biomarkers for thrombotic complications is promising. Future advances in detection methods will likely provide more insight into TFMP and eventually improve their clinical utility.
    Seminars in Thrombosis and Hemostasis 09/2015; DOI:10.1055/s-0035-1556047
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    ABSTRACT: Protein disulfide isomerase (PDI) is a 57-kDa oxidoreductase that facilitates cysteine thiol reactions inside and outside the cell. It mediates reduction or oxidation of protein disulfide bonds, thiol/disulfide exchange reactions, and transfer of NO from one protein thiol to another. It also has chaperone properties. PDI is actively secreted by most, if not all, of the cell types involved in thrombosis, binds to integrins on the cell surface, and circulates as a soluble protein in blood. It plays a critical role in thrombosis in mice and presumably the same role in human thrombosis. Eight proteins involved in thrombosis have been identified as PDI substrates; however, the role of this oxidoreductase in this process is not fully understood. Novel small-molecule PDI inhibitors have been developed and are being evaluated as antithrombotics in clinical trials. This combination of ongoing laboratory and clinical studies will greatly accelerate the pace of discovery and targeting of PDI function in thrombosis.
    Seminars in Thrombosis and Hemostasis 09/2015; DOI:10.1055/s-0035-1564047
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    ABSTRACT: Interactions between tissue factor and factor VIIa are the primary initiators of coagulation in hemostasis and certain thrombotic diseases. Tissue factor, an integral membrane protein expressed extensively outside of the vasculature, is the regulatory protein cofactor for coagulation factor VIIa. Factor VIIa, a trypsin-like serine protease homologous with other blood coagulation proteases, is weakly active when free in solution and must bind its membrane-bound cofactor for physiologically relevant activity. Tissue factor allosterically activates factor VIIa by several mechanisms such as active site positioning, spatial stabilization, and direct interactions with the substrate. Protein-membrane interactions between tissue factor, factor VIIa, and substrates all play critical roles in modulating the activity of this enzyme complex. Additionally, divalent cations such as Ca(2+) and Mg(2+) are critical for correct protein folding, as well as protein-membrane and protein-protein interactions. The contributions of these factors toward tissue factor-factor VIIa activity are discussed in this review.
    Seminars in Thrombosis and Hemostasis 09/2015; DOI:10.1055/s-0035-1564044
  • Seminars in Thrombosis and Hemostasis 09/2015; 41(6):547-8. DOI:10.1055/s-0035-1556724
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    ABSTRACT: The diversity of integrins and their complex role in many diseases suggests great potential for this superfamily as drug targets. The initial successes of anti-integrin therapeutics in the treatment of thrombotic disorders suggested that similar anti-integrin agents could be developed for the treatment of inflammatory disorders. While initially a promising strategy, inhibition of the integrins proved to be elusive despite the discovery of highly potent inhibitors. This is due to several reasons, including redundancy among the integrins and the importance of integrins in key physiological systems. Further exploration of the selective role for distinct leukocytic integrins indicated that homing of inflammatory cells to select disease sites depends on a highly regulated expression of discrete integrins and their ligands in limited locations. Selective control of integrin function is also regulated by local chemokines permitting exquisite homing of populations of inflammatory cells to disease sites. A more complete understanding of the regulation of integrin activation in disease states will permit the development of more effective and specific anti-integrin therapeutic agents. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
    Seminars in Thrombosis and Hemostasis 08/2015; DOI:10.1055/s-0035-1556588
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    ABSTRACT: Venous thromboembolic disease often arises as a complication of another pathological condition and/or triggering event. Infectious diseases result from both the direct action of the pathogens themselves and their effect on the immune system. The resulting inflammatory process and the coagulation and fibrinolysis processes share common pathways, explaining why infection is associated with thrombosis. In this brief overview, besides certain chronic infectious diseases, we also consider some acute infections, as the mechanisms are likely to be similar, particularly in the initial infective stage or the more acute episodes of a chronic infection. The infectious agent can be viral, bacterial, fungal, or parasitic. However, the literature on the link between infections and venous thromboembolism (VTE) is uneven, favoring infections that are found in more developed countries where physicians have access to VTE diagnostic tools. Thus, large epidemiological studies in this field are restricted to a limited number of the common chronic infectious diseases such as tuberculosis, while for other infections, particularly parasitic and fungal infections, the link with VTE is only evoked in a few scattered case reports. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
    Seminars in Thrombosis and Hemostasis 08/2015; DOI:10.1055/s-0035-1556729
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    ABSTRACT: It is well established that inflammation and thrombosis are intricately linked processes, and there is increasing evidence of the importance of their roles in activated complement in the pathogenesis of thromboembolism. The two systems are activated by similar stimuli simultaneously and interact, either directly or through biochemical mediators, to protect the host from microbial invasion. Diseases characterized by complement hyperactivity such as paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome have high rates of thrombosis. This review describes how disease processes where there is excessive complement activation leads to thrombosis, and the specific interactions between the complement and coagulation systems that lead to pathological thrombus formation. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
    Seminars in Thrombosis and Hemostasis 08/2015; DOI:10.1055/s-0035-1556732
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    ABSTRACT: Endothelial cells are unique multifunctional cells with basal and inducible metabolic and synthetic functions. Various stimuli can induce physiological or pathological changes in endothelial cell biology. Hematopoietic stem cell transplantation (HSCT) requires high-dose irradiation and/or chemotherapy and is associated with increased risk of bacterial infections and immune reactions. These factors can affect endothelial cells. This review provides an overview of the effects of HSCT on endothelial cells, based on findings observed in cultured cells as well as in patients. We first describe to what extent irradiation and chemotherapy constitute direct and indirect triggers for endothelial cell activation and injury. Then, we highlight the role of the endothelium in several complications of HSCT, including capillary leak syndrome, engraftment syndrome, transplant-associated microangiopathy, graft-versus-host disease, and diffuse alveolar hemorrhages. We also analyze in detail available data on sinusoidal obstruction syndrome, previously known as veno-occlusive disease of the liver, where liver sinusoidal endothelial cells are first injured and eventually lead to sinusoid occlusion and liver cell damage. Finally, we open the question of the possible contribution of endothelial damage to cardiovascular events occurring long after HSCT. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
    Seminars in Thrombosis and Hemostasis 08/2015; DOI:10.1055/s-0035-1556728
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    ABSTRACT: Thrombotic microangiopathy (TMA) is characterized by the presence of microangiopathic hemolytic anemia and thrombocytopenia. There are several disorders with varied etiopathogenesis, both genetic and acquired, that result in TMA. The neutrophils play an important role in inflammation and thrombosis through the formation of neutrophil extracellular traps (NETs). NETs are formed in response to a variety of stimuli including infections, chemical factors, and platelet activation. The classic TMA, thrombotic thrombocytopenic purpura (TTP) is caused by a severe deficiency of ADAMTS-13 (a disintegrin and metalloproteinase with a thrombospondin type-I motif, member 13), mostly acquired due to autoantibodies, whereas atypical hemolytic uremic syndrome (aHUS) is mostly attributed to genetic defects in complement pathway regulatory proteins. The management of these well-known disorders has evolved over the last decade. Similarly, there is also better understanding of diverse and unusual clinical presentations of both of these conditions. Since there are many other causes of TMAs, which may mimic some of the clinical features of TTP or aHUS, it is essential to thoroughly investigate each patient so that appropriate therapy can be offered. This review focuses on some important developments in understanding of etiopathogenesis, diagnosis, and treatment of more commonly encountered TMAs. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
    Seminars in Thrombosis and Hemostasis 08/2015; DOI:10.1055/s-0035-1556587
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    ABSTRACT: Behçet disease (BD) is a rare multisystem, inflammatory disease of unknown etiology with vascular involvement and associated thrombogenicity. This review aims to describe the involvement of various mediators in endothelial cell damage and in the hypercoagulable state of BD. The scenario of the chronic inflammation present in BD shows an increased oxidative condition that contributes to endothelial cell damage and induces platelet, leukocyte, and endothelial cell activation through the release of proinflammatory cytokines and chemokines. These factors, together with the increased levels of homocysteine observed in BD patients, induce the endothelial cell expression of adhesion molecules (VCAM-1 and ICAM-1) and tissue factor; the release of cytokines, soluble CD40L (sCD40L), matrix metalloproteinase-9, and blood coagulation factor V; the inhibition of fibrinolysis; the disruption of nitric oxide metabolism; and the increase in platelet reactivity and lipid peroxidation. Endothelial cell dysfunction leads to a prothrombotic and antifibrinolytic phenotype in BD patients. Increased levels of homocysteine, fibrinogen, and plasminogen activator inhibitor type 1 seem to be involved in the procoagulant condition of this pathology that has been verified by end-point tests as well as by global coagulation tests. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
    Seminars in Thrombosis and Hemostasis 08/2015; DOI:10.1055/s-0035-1556727