Seminars in Thrombosis and Hemostasis

Publisher: Thieme Publishing

Description

  • Impact factor
    4.22
  • 5-year impact
    3.84
  • Cited half-life
    5.20
  • Immediacy index
    2.00
  • Eigenfactor
    0.01
  • Article influence
    1.06
  • ISSN
    1098-9064
  • OCLC
    163849709
  • Material type
    Internet resource
  • Document type
    Internet Resource, Computer File, Journal / Magazine / Newspaper

Publisher details

Thieme Publishing

  • Pre-print
    • Author cannot archive a pre-print version
  • Post-print
    • Author can archive a post-print version
  • Conditions
    • Authors and Publishers version on author's personal web site
    • Institutional Repository (including PubMed Central) after 12 months
    • Publisher's version/PDF cannot be used
    • Publisher copyright and source must be acknowledged
    • Link to Publisher version (www.thieme-connect.com) must be included if article has been published online
  • Classification
    ​ blue

Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: Factor XIII/13 (FXIII or F13) is a plasma protransglutaminase, which stabilizes fibrin clots, and thus plays an important role in hemostasis. Autoimmune hemo(rrha)philia due to anti-F13 autoantibodies (AH13) has been on the rise in Japan, which has become the leading superaging society in the 21st century. The mean age of Japanese AH13 cases has risen to 70.4 years. A total of 83 AH13 cases have been diagnosed in the world as of July 2014. To raise the awareness of AH13, the author and members of the Japanese Collaborative Research Group first proposed "Criterion and Algorithm of Laboratory Tests for anti F13" in February 2012. AH13 is not just an acquired isolated defect of F13 molecule itself but a disturbance caused by autoantibodies. Accordingly, AH13 cases are diagnosed in patients with otherwise unexplained hemorrhages by a combination of a severe deficiency of F13 activity and the presence of anti-F13 autoantibodies. As patients with this disease manifest life-threatening bleeding symptoms, prompt diagnosis and proper treatment are essential. Because AH13 tends to become chronic and intractable, affected patients must be closely followed for a prolonged period.
    Seminars in Thrombosis and Hemostasis 09/2014;
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    ABSTRACT: The risk for both arterial and venous thrombosis increases with age. Despite the increasing burden of strokes related to atrial fibrillation (AF) and venous thromboembolism (VTE) among older adults, the use of anticoagulant therapy is limited in this population due to the parallel increase in risk of serious hemorrhage. Understanding the risks and their underlying mechanisms would help to mitigate adverse events and improve persistence with these life-saving therapies. The objectives of this review are to: (1) elucidate the age-related physiologic changes that render this high risk subgroup susceptible to hemorrhage, (2) identify mutable risk factors and hazards contributing to an increased bleeding risk in older individuals, and (3) discuss interventions to optimize anticoagulation therapy in this population.
    Seminars in Thrombosis and Hemostasis 09/2014;
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    ABSTRACT: Microparticles (MPs) are membrane-bound vesicles with important physiologic effects. MPs exchange information intercellularly, with each kind of MP carrying antigens and receptors of the cells from which they originated. They are biologic effectors in inflammation, angiogenesis, vascular injury, and thrombosis. Thrombosis is generally caused by abnormalities in blood flow, blood composition, and/or properties of the vessel wall. Thrombosis is a well-described feature of cardiovascular disease and cerebrovascular disease. Accumulating evidence suggests that increased risk of thrombosis is also characteristic of autoimmune disorders and immune-mediated diseases affecting all age groups, although the older adults are most vulnerable. Current research has also implicated MPs as a source of autoantigenic nuclear material that can form immune complexes, activate the innate immune system, and may lead to autoimmunity. This review focuses on the contribution of MPs to both the pathogenesis of autoimmune diseases and, as the immune and coagulation systems are tightly linked, their role in hypercoagulability in the setting of autoimmunity in an aging population.
    Seminars in Thrombosis and Hemostasis 08/2014;
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    ABSTRACT: The average age of the US population continues to increase. Age is the most important determinant of disease and disability in humans, but the fundamental mechanisms of aging remain largely unknown. Many age-related diseases are associated with an impaired fibrinolytic system. Elevated plasminogen activator inhibitor-1 (PAI-1) levels are reported in age-associated clinical conditions including cardiovascular diseases, type 2 diabetes, obesity and inflammation. PAI-1 levels are also elevated in animal models of aging. While the association of PAI-1 with physiological aging is well documented, it is only recently that its critical role in the regulation of aging and senescence has become evident. PAI-1 is synthesized and secreted in senescent cells and contributes directly to the development of senescence by acting downstream of p53 and upstream of insulin-like growth factor binding protein-3. Pharmacologic inhibition or genetic deficiency of PAI-1 was shown to be protective against senescence and the aging-like phenotypes in kl/kl and N(ω)-nitro-l-arginine methyl ester-treated wild-type mice. Further investigation into PAI-1's role in senescence and aging will likely contribute to the prevention and treatment of aging-related pathologies.
    Seminars in Thrombosis and Hemostasis 08/2014;
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    ABSTRACT: Inherited macrothrombocytopenias are a clinically heterogeneous group of disorders, many of which cause moderate-to-severe bleeding tendencies in affected individuals, but which remain under-recognized and are frequently misdiagnosed as immune thrombocytopenia purpura. Diagnostic strategies to date have included a predominant phenotypic approach. The emergence of genetic testing and the implementation of next generation sequencing strategies in the investigation and diagnosis of these disorders have broadened our understanding of their pathogenesis, classification, and presentation. This review describes the increasingly expanding group of recognized inherited macrothrombocytopenias and highlights their pathophysiology and the role of phenotypic and genetic testing in their description and diagnosis.
    Seminars in Thrombosis and Hemostasis 08/2014;
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    ABSTRACT: The nitric oxide (NO)/soluble guanylate cyclase (sGC) system is fundamental to endothelial control of vascular tone, but also plays a major role in the negative modulation of platelet aggregation. The phenomenon of platelet NO resistance, or decreased antiaggregatory response to NO, occurs increasingly with advanced age, as well as in the context of cardiovascular disease states such as heart failure, ischemic heart disease, and aortic valve disease. The central causes of NO resistance are "scavenging" of NO and dysfunction of sGC. In the current review, we discuss the roles of several modulators of NO synthesis and of the NO/sGC cascade on changes in platelet physiology with aging, together with potential therapeutic options to reduce associated thrombotic risk.
    Seminars in Thrombosis and Hemostasis 08/2014;
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    ABSTRACT: Nucleic acids (NAs) constitute the backbone of cellular life permitting conservation, transmission, and execution of genetic information. In the past few years, new unexpected functions for NAs, projecting them also beyond nuclear and cellular boundaries have been recognized: circulating cell-free nucleic acids (cfNAs), histones, DNA-histone complexes, microRNAs (miRs) may have a regulatory role in physiological and pathological processes. In particular, several lines of evidence suggest that they can constitute unconventional mediators of thrombus formation, intervening both in hemostasis and thrombosis. Furthermore, in the past decade, the possibility to detect and quantify these in plasma and/or in serum has led to their ancillary use as potential markers in various medical conditions. The use of these as markers within the fields of thrombosis and hemostasis looks promising: the potential implications include the possibility to assess patients' risk profiles for thrombotic events and the identification of more directed targets for pharmacologic intervention. The major impediment is that, to date, the methods by which NAs are explored, still largely differ between published studies and standardized procedures are still lacking. Future research should focus on the physiological mechanisms underlying the activities of such mediators in specific thrombotic conditions and on the definition of reliable methods for their quantification in biological fluids.
    Seminars in Thrombosis and Hemostasis 08/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: Aging is associated with many physiological changes, which may in time lead to numerous pathophysiological outcomes, including adverse vascular events. For example, senescence of the immune system and cellular senescence both contribute to rising inflammation with age, potentially induced by the overall burden of comorbid illness, adipose tissue mass, diet, socioeconomic status, and physical activity. In turn, this chronic inflammation decreases physical and cognitive performance, and promotes sarcopenia and the syndrome of frailty. These events and others decrease the functionality of life as we age and include an increased risk of thrombosis and adverse cardiovascular outcomes. In this review, we aim to overview the aging process primarily as related to functional impairment, and provide evidence for the role of protein, and specifically differential quality protein, in particular whey protein, and timing and distribution of intake, to help reduce some of the morbid effects of aging, including reducing obesity, improving glycemic control, and improving vascular function.
    Seminars in Thrombosis and Hemostasis 08/2014;
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    ABSTRACT: von Willebrand factor (VWF) plays critical roles in initiating primary hemostasis and extending the half-life of coagulation factor VIII in circulation. VWF levels increase with age and elevated levels are associated with an increased risk of venous thromboembolism and cardiovascular disease (CVD). Patients with von Willebrand disease (VWD) due to a deficiency or dysfunction of VWF may have symptoms that ameliorate with aging or may have exacerbation of their disease. Bleeding sites of particular challenge in the aging patient include gastrointestinal bleeding and hematuria. Some medications used to treat VWD should be used with special precaution in older patients, including desmopressin and VWF-containing factor concentrates. Patients with VWD may have some protection from CVD, but in those patients who develop CVD, management is very challenging, given the role of antiplatelet therapy as the mainstay of treatment.
    Seminars in Thrombosis and Hemostasis 08/2014;
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    ABSTRACT: The available evidence suggests that immunosenescence induces organismal proinflammatory responses. The chronic inflammation seen in advancing age stratifies persons into aging phenotypes. Even with adjustment for confounders, elevated inflammatory cytokines significantly decrease the odds of successful aging. This chronic inflammation seen in advancing age has varied causes, including comorbid illness, adipose tissue mass, diet, socioeconomic status, body mass index, gender, age, and physical activity. Aging can therefore be thought of as an acquired thrombophilia of increasing inflammation, impaired fibrinolytic potential, and a hypercoagulable state, out of proportion to physiological needs. Factors ranging from genetic to environmental contribute to the prothrombotic tendency of aging adults, especially those with concomitant frailty, to experience a decline in health status.
    Seminars in Thrombosis and Hemostasis 08/2014;
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    ABSTRACT: Thrombocytopenia in older patients is associated with several characteristics that are often underrecognized. Among them are the risk of bleeding complications, the senescence of the bone marrow, the increased use of multiple drugs, and greater comorbidity. In this article, the various forms of thrombocytopenia, including primary and drug-associated immune thrombocytopenias, as well as other drug-associated thrombocytopenias, are reviewed. In addition, how age-related changes in platelet function may affect the bleeding risk is discussed.
    Seminars in Thrombosis and Hemostasis 08/2014;
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    ABSTRACT: The introduction of new hemophilia management therapies, targeting extended half-lives through bioengineering, ushers in an era of potential promise and increasing complexity, more so for those with hemophilia B than hemophilia A. Questions arise for patients, caregivers, and hemophilia treatment center (HTC) staff about how to assess and incorporate novel therapies and how to determine whether new therapies offer a distinct advantage over established treatment routines. Nurses and other interdisciplinary HTC staff are well positioned to assess, educate, and support patients and families in navigating this rapidly changing landscape. To support these challenging efforts, this review offers a perspective on issues affecting therapeutic transitions and provides tools to foster ongoing adherence.
    Seminars in Thrombosis and Hemostasis 08/2014;
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    ABSTRACT: Plasminogen activator inhibitor-1 (PAI-1), a principal inhibitor of fibrinolysis, is induced in thrombotic, fibrotic, and cardiovascular diseases, which in turn primarily afflict the older population. This induction of PAI-1 may play an important role in the pathology of these diseases as PAI-1 can regulate the dissolution of fibrin and also inhibit the degradation of the extracellular matrix by reducing plasmin generation. PAI-1 expression is elevated in aged individuals and is significantly upregulated in a variety of pathologies associated with the process of aging, including myocardial and cerebral infarction, vascular (athero) sclerosis, cardiac and lung fibrosis, metabolic syndromes (e.g., hypertension, hyperlipidemia, and insulin resistance), cancer, and inflammatory/stress responses. Thus, PAI-1 may play a critical role in the development of aging-associated pathological changes. In addition, PAI-1 is recognized as a marker of senescence and a key member of a group of proteins collectively known as the senescence-messaging secretome. In this review, we highlight the role of PAI-1 in the pathophysiology of aging and aging-associated disorders.
    Seminars in Thrombosis and Hemostasis 08/2014;
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    ABSTRACT: Great advances have been made in our understanding of the fibrinolytic system from the initial discovery of proteolysis of fibrin by plasmin to the multifaceted and complex role of the plasminogen-plasmin (P-P) system. We now know that the P-P system is composed of several serine proteases and their inhibitors (serpins). This system is involved in many physiological functions, including embryogenesis, cell migration, and wound healing. They also play an important role in the pathogenesis of many diseases, including atherosclerosis, obesity, cancer, and even autoimmune disorders, and neuronal degeneration. Knowledge of their role in cancer enables their use as a prognostic factor. Therapeutic use of various forms of proteases derived from this system has been employed as thrombolytic agents. In addition, small molecules designed to inhibit many of the components of the P-P system are now available for clinical trial, aimed at treatment of these various disorders. The history of such remarkable development of our knowledge on fibrinolysis is reviewed in this article.
    Seminars in Thrombosis and Hemostasis 07/2014;
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    ABSTRACT: von Willebrand disease (VWD) is a disorder characterized by deficiency of, or defects in, von Willebrand factor (VWF). VWD was originally identified by Erik Adolf von Willebrand, who in early 1924 investigated a large family suffering from a bleeding disorder that seemed to differ from hemophilia. Erik von Willebrand undertook some initial laboratory investigations to conclude the involvement of a plasma factor, the lack of which prolonged the bleeding time, but failed to impair coagulation times and clot retraction. By the end of the 1960s, VWD was accepted as a combined deficiency of factor VIII (FVIII) and another plasma factor responsible for normal platelet adhesion. Just how these two functions were related to each other was less clear and the diagnostic tests available at the time were poorly reproducible, cumbersome, and unreliable; thus, VWD was poorly delineated from other coagulation and platelet disorders. The early 1970s saw a revolution in diagnostics when ristocetin was identified to induce platelet aggregation, and this formed the basis of the first consistent and reliable VWF "activity" test, permitting quantification of the platelet adhesive function missing in VWD. Concurrently, immunoprecipitating techniques specific for VWF were defined, and the application of such technologies permitted a clearer understanding of both VWF and VWD heterogeneity. Continued exploration of the structure and function of VWF contributed greatly to the understanding of platelet physiology, ligand receptor interaction and pathways of cellular interaction and activation. Recently, additional assays evaluating other functions of VWF, including collagen binding, platelet glycoprotein Ib binding, and FVIII binding, have improved the diagnosis of VWD. The purpose of this narrative review is to explore the history of phenotypic VWD diagnostics, with a focus on laboratory milestones from the past as well highlighting recent and ongoing innovations, and ongoing challenges and possible solutions.
    Seminars in Thrombosis and Hemostasis 06/2014;
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    ABSTRACT: There has been rapid progress in the understanding of the pathophysiology of the hemolytic uremic syndrome (HUS) disease spectrum; thus, complex diagnostic and therapeutic requirements have emerged in parallel. Current recommendations for diagnosis and therapy were rapidly adapted from the prior skilled scientific groundwork. However, such recommendations can be realized only when highly specialized laboratories and sufficient financial resources are available. Thus, many recommendations are not feasible for patients living and working in developing countries. More than one-third of the world's population has no access to essential drugs and more than half of this group lives in the poorest regions of Africa and Asia. From this perspective, distinct initial diagnostic and therapeutic recommendations, as well as international cooperations are needed to complete proper diagnostic work-ups in a stringent and cost-efficient manner and to enable patients to be adequately treated with available resources. However, while costs for complement-targeted drugs remain tremendously high, state-of-the-art treatment options remain unavailable for the vast majority of patients in developing areas.
    Seminars in Thrombosis and Hemostasis 05/2014;
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    ABSTRACT: Congenital thrombotic thrombocytopenic purpura (TTP) or Upshaw-Schulman syndrome is caused by homozygous or compound heterozygous mutations in the ADAMTS-13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) gene. We investigated 30 patients with congenital TTP and analyzed clinical data and underlying ADAMTS-13 mutations. All patients showed virtually no ADAMTS-13 activity in plasma. Individual disease burden ranged from mild courses with rare episodes of mild thrombocytopenia to severe courses with chronic kidney disease and central nervous system (CNS) lesions. Two patients died due to complications of TTP. If initiated in a timely manner, plasma transfusions offer a reliable treatment to prevent organ damage. We identified 30 different causative mutations in the ADAMTS-13 gene. Our data do not support the idea of a tight correlation between ADAMTS-13 genotype and severity of disease. The type and magnitude of exogenous triggers for acute bouts of TTP as well as endogenous individual factors participating in the inflammatory response likely represent the foremost determinants of individual clinical courses. Future developments should aim at improving early diagnosis of TTP. To improve feasibility of prophylaxis and treatment of congenital TTP, recombinant ADAMTS-13 therapeutics are highly anticipated.
    Seminars in Thrombosis and Hemostasis 05/2014;
  • Seminars in Thrombosis and Hemostasis 05/2014;

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