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

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    • On Institutional Repository and PubMed Central after 12 months embargo
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  • Classification
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Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: A reduction in bleeding pattern and arthropathy appears to be observed in approximately 10% of the patients with severe hemophilia (< 1% clotting factor activity). These patients rarely bleed and do not always need prophylactic therapy of therapeutic products, resulting in the wide range of joint damage seen in patients with severe hemophilia. The cause(s) of this phenotypic heterogeneity has been investigated in many studies till date, but remains to be completely solved. The large heterogeneity of the clinical phenotype in severe hemophilia seems to be multifactorial, including variation in the levels of various procoagulant and anticoagulant factors, the balance between the coagulation and fibrinolysis systems, pharmacokinetics of therapeutic products, environmental factors including lifestyle activity, and the limitation of measurement at lower levels of clotting factors. As an approach toward clarification, studies should be designed to evaluate a homogenous cohort of hemophilic A patients with an intron 22 inversion who produce no factor VIII. In the future, by a combination of the measurement of lower levels of clotting factors and the evaluation of global clotting function, it might be possible to better grasp the potential of hemostatic coagulation in individual hemophilia patients, which should in turn be useful for the prediction of bleeding phenotype and the designation of adequate and long-term hemostatic management throughout their life. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
    Seminars in Thrombosis and Hemostasis 01/2015;
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    ABSTRACT: Point-of-care (POC) testing in hemostasis has experienced a significant increase in the spectrum of available tests and the number of tests performed. Short turn-around time and observation of rapid changes in test results are facilitated. The quality control process in POC testing must encompass a preanalytic (collection), analytic (measurement), and postanalytic (clinical response) phase. Erroneous interpretation of findings and difficult quality controls can outweigh the advantages of POC testing.Only a limited number of hemostatic POC tests have proven useful so far: prothrombin time POC-monitoring of oral vitamin K antagonists; activated clotting time POC-monitoring of high-dose heparin therapy; platelet function analyzer (PFA; Siemens, Marburg, Germany) closure time (CT)-detection of von Willebrand disease and severe platelet function defects; whole blood aggregometry (WBA) Multiplate (Roche Diagnostics, Rotkreuz, Switzerland), and the VerifyNow system (Accumetrics, San Diego, CA)-detection of platelet dysfunction due to antiplatelet drugs; thromboelastography-continuous observation of clot formation and fibrinolysis. The use of various agonists in WBA and thromboelastography (TEG) requires some expertise. In experienced hands the PFA CT and WBA and TEG are recommended combinations.Application of POC testing depends strictly on whether it improves medical care and patient outcome. More POC test systems are in the research pipeline, but only a few will resist the ravages of time. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
    Seminars in Thrombosis and Hemostasis 01/2015;
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    ABSTRACT: Hemostasis and thrombosis in trauma patients consist of physiological hemostasis for wound healing and the pathological reaction of disseminated intravascular coagulation (DIC). Whole body trauma, isolated brain injury, and fat embolism syndrome, if extremely severe, can cause DIC and affect a patient's prognosis. Shock-induced hyperfibrinolysis causes DIC with the fibrinolytic phenotype, contributing to oozing-type severe bleeding. If uncontrolled, this phenotype progresses to thrombotic phenotype at the late stage of trauma, followed by microvascular thrombosis, leading to organ dysfunction. Another type of pathological hemostatic change is acute coagulopathy of trauma shock (ACOTS), which gives rise to activated protein C-mediated systemic hypocoagulation, resulting in bleeding. ACOTS occurs only in trauma associated with shock-induced hypoperfusion and there is nothing to suggest DIC in this phenomenon. This review will provide information about the recent advances in hemostasis and thrombosis in trauma and will clarify the pathogeneses of the pathological processes observed in trauma patients. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
    Seminars in Thrombosis and Hemostasis 01/2015;
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    ABSTRACT: Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), is recognized as a common complication in critically ill patients. Risk factors including critical illness, mechanical ventilation, sedative medications, and central venous catheter insertion are major contributing factors to the high risk of VTE. Because of their impaired cardiopulmonary reserve, PE arising from thrombosis in the deep veins of the calf that propagates proximally is poorly tolerated by critically ill patients. Pharmacologic prophylaxis with unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH) has been shown to decrease the incidence of VTE in medical, surgical, and critically ill patients. As a result, over the past decades, VTE prophylaxis had become a standard of preventive measure in the intensive care unit (ICU). In clinical practice, the rate of VTE prophylaxis varies and may be inadequate in some centers. A perception of a high bleeding risk in critically ill patients is a major concern for most physicians that may lead to inadequate prophylaxis. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
    Seminars in Thrombosis and Hemostasis 01/2015;
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    ABSTRACT: The patients who do not respond even to very high dosages of heparin are assumed to suffer from heparin resistance. The aim of this study was to investigate whether critically ill patients suffering from heparin resistance generally have low antithrombin III (AT) levels, and if the direct thrombin inhibitor argatroban in that case can be an effective option to achieve prophylactic anticoagulation. The study was conducted at the Department for General and Surgical Intensive Care Medicine at the University Hospital Innsbruck. We retrospectively included all patients between 2008 and 2012, who received argatroban because of poor response to high-dosage heparin prophylaxis. The period under observation lasted in total for 9 days, 2 days of anticoagulation with unfractionated heparin (UFH) and 7 days with argatroban. The primary objective was to investigate if after 7 (± 1) hours of switching to argatroban the activated partial thromboplastin time (aPTT) levels were in a prophylactic range of 45 to 55 seconds. Further objectives were to assess the AT level, side effects such as bleeding or thromboembolism, platelet count, correlation between organ function and argatroban dose as well as any need for allogeneic blood products. The study population, consisting of 5 women and 15 men with a mean (± standard deviation, SD) age of 54.6 ± 16.3 years, differed in many clinical aspects. A median (interquartile range) heparin dose of 1,000, 819 to 1,125 IU/h was administered for 2 days and failed in providing a prophylactic anticoagulation measured by the aPTT. The mean aPTT level with heparin treatment was 38.5 seconds (± 4.7) its change within that period was not significant. After switching to argatroban, the mean increase of the aPTT levels in all study patients amounted from 38.5 to 48.3 seconds (p < 0.001). The rise in aPTT clearly reaches sufficient prophylactic anticoagulant levels. The maintenance of prophylactic aPTT levels was achieved over the period of 1 week. There was neither a correlation found between low-AT levels and occurrence of heparin resistance, nor between the simplified acute physiology score II and the administered argatroban dose (r = -0.224, p = 0.342). The results of the present study indicate that argatroban is an effective alternative therapy, especially in critically ill patients, to achieve prophylactic anticoagulation when heparin resistance occurs. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
    Seminars in Thrombosis and Hemostasis 01/2015;
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    ABSTRACT: Cardiac surgery with cardiopulmonary bypass determines a serious imbalance of the hemostatic system. The clinical pattern is multifactorial, involving patient-related, drug-related, and surgery-related factors. As a result, the patient is prone to both hemorrhagic and thrombotic complications. To address the clinical management of a bleeding patient after cardiac surgery, avoiding empirical administration of drugs and blood derivates, it is mandatory to correctly identify the factor(s) responsible for bleeding. Bleeding after cardiac operations can be ascribed to seven basic mechanisms: residual heparin effect; reduced thrombin generation; fibrinogen deficiency; thrombocytopenia; platelet dysfunction; hyperfibrinolysis; and surgical sources. These factors may interact together, creating a complex coagulopathy. Point-of-care coagulation tests are useful to orienteer the clinician in this complex scenario. Viscoelastic coagulation tests find their greater usefulness in the diagnosis of the bleeding mechanism(s), whereas platelet function tests appear more useful for the preoperative assessment of patients under the effects of antiplatelet agents. Thromboembolic complications are the other side of the coin, and their prevention is still a matter of debate. Consumption of natural anticoagulants and endothelial disturbance are important mechanisms underlying this condition. Strategies to limit antithrombin (AT) consumption or to correct low postoperative levels of AT are still a matter of discussion. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
    Seminars in Thrombosis and Hemostasis 01/2015;
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    ABSTRACT: In the majority of patients with severe sepsis, systemic activation of coagulation is present. Increasing evidence points to an extensive cross-talk between coagulation and inflammation that may play an important role in the pathogenesis of sepsis. Inflammation not only leads to activation of coagulation, but coagulation also considerably affects inflammatory activity. Molecular pathways that contribute to inflammation-induced activation of coagulation have been precisely identified. Proinflammatory cytokines and other mediators are capable of activating the coagulation system and downregulating important physiological anticoagulant pathways. Activation of the coagulation system and ensuing thrombin generation is dependent on expression of tissue factor on activated mononuclear cells and endothelial cells, and is insufficiently counteracted by TFPI. Simultaneously, endothelial-bound anticoagulant mechanism, in particular the protein C system, is shutoff by proinflammatory cytokines. In addition, fibrin removal is severely inhibited, because of inactivation of the fibrinolytic system, caused by an upregulation of its main inhibitor, plasminogen activator inhibitor type 1 (PAI-1). Increased fibrin formation and impaired removal lead to (micro)vascular thrombosis, which may result in tissue ischemia and subsequent organ damage. The cornerstone of the management of coagulation in sepsis is the specific and vigorous treatment of the underlying disorder. Strategies aimed at the inhibition of coagulation activation may theoretically be justified and have been found beneficial in experimental and initial clinical studies. Heparin may be an effective anticoagulant approach and alternative strategies comprise restoration of physiological anticoagulant pathways. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
    Seminars in Thrombosis and Hemostasis 01/2015;
  • Maria E Johansen, Pär I Johansson, Sisse R Ostrowski, Morten H Bestle, Lars Hein, Anne L G Jensen, Peter Søe-Jensen, Mads H Andersen, Morten Steensen, Thomas Mohr, Katrin Thormar, Bettina Lundgren, Alessandro Cozzi-Lepri, Jens D Lundgren, Jens-Ulrik Jensen
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    ABSTRACT: Endothelial damage contributes to organ failure and mortality in sepsis, but the extent of the contribution remains poorly quantified. Here, we examine the association between biomarkers of superficial and profound endothelial damage (syndecan-1 and soluble thrombomodulin [sTM], respectively), organ failure, and death in sepsis. The data from a clinical trial, including critically ill patients predominantly suffering sepsis (Clinicaltrials.gov: NCT00271752) were studied. Syndecan-1 and sTM levels at the time of study enrollment were determined. The predictive ability of biomarker levels on death and organ failures during follow-up were assessed in Cox models adjusted for potential confounders including key organ dysfunction measures assessed at enrollment. Of the 1,103 included patients, 418 died. sTM levels at the time of enrollment independently predicted risk of death in adjusted models (hazard ratio [HR] [highest quartile > 14 ng/mL vs. lowest quartile < 7 ng/mL] 2.2 [95% confidence interval [CI]: 1.2-4.0], p = 0.02, respectively). Conversely, syndecan-1 levels failed to predict death (adjusted HR [> 240 vs. < 70 ng/mL] 1.0 [95% CI: 0.6-1.5], p = 0.67). sTM but not syndecan-1 levels at enrollment predicted risk of multiple organ failure during follow-up (HR [> 14 ng/mL vs. < 7 ng/mL] 3.5 [95% CI: 1.5-8.3], p = 0.005 and 2.0 [95% CI: 0.8-5.0], p = 0.1321, respectively). Profound damage to the endothelium independently predicts risk of multiple organ failure and death in septic patients. Our findings also suggest that the detrimental effect of profound endothelial damage on risk of death operates via mechanisms other than causing organ failures per se. Therefore, damage to the endothelium appears centrally involved in the pathogenesis of death in sepsis and could be a target for intervention. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
    Seminars in Thrombosis and Hemostasis 01/2015;
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    ABSTRACT: During continuous renal replacement therapy, the delicate equilibrium of hemostasis is disturbed. Owing to a complex interaction of critical illness, uremia, use of an extracorporeal circuit and anticoagulation, patients exhibit both hypercoagulability and an increased risk of bleeding. Contact of blood with foreign material initiates coagulation by triggering the contact activation coagulation pathway, the tissue factor-factor VIIa pathway and activation of platelets and monocytes, which adhere to the membrane. The interaction with critical illness induced alterations further enhances coagulation and inflammation. Classical markers of coagulation, prothrombin and activated thromboplastin time, and platelet count do not detect the procoagulant state. Critically ill patients also have in increased risk of bleeding and anticoagulation used for circuit clotting enhances this risk. Heparin is most commonly used. Heparin increases the risk of bleeding. Its efficacy and safety are further compromised by antithrombin deficiency, heparin binding to acute phase proteins and apoptotic and necrotic cells, and by its unpredictable effects on inflammation. Its interference with anticoagulation is therefore unreliable during critical illness. Citrate provides regional anticoagulation and increases biocompatibility. It is better tolerated than heparin and confers less bleeding, less transfusion, and longer circuit life. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
    Seminars in Thrombosis and Hemostasis 01/2015;
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    ABSTRACT: The liver plays an important role in the balance between hemostasis and thrombosis. Hepatic resection, particularly when performed in the presence of underlying parenchymal liver disease, can cause perturbation of this balance. This review summarizes the changes that occur in normal hemostasis and thrombosis before, during, and after nontransplant hepatic resection and, wherever possible, provides strategies for the perioperative management of bleeding and thrombosis. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
    Seminars in Thrombosis and Hemostasis 01/2015;
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    ABSTRACT: To our knowledge, this is the first comprehensive review on the subject of venous thromboembolism (VTE) and hypercoagulability in burn patients. Specific changes in coagulability are reviewed using data from thromboelastography and other techniques. Disseminated intravascular coagulation in burn patients is discussed. The incidence and risk factors associated with VTE in burn patients are then examined, followed by the use of low-molecular-weight heparin thromboprophylaxis and monitoring techniques using antifactor Xa levels. The need for large, prospective trials in burn patients is highlighted, especially in the areas of VTE incidence and safe, effective thromboprophylaxis. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
    Seminars in Thrombosis and Hemostasis 01/2015;
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    ABSTRACT: For patients taking vitamin K antagonist (VKA) anticoagulants, poor adherence to the drug regimen is associated with a lower percent time in therapeutic range and also with an increased risk of thromboembolic complications. The non-vitamin K antagonist oral anticoagulants (NOACs) do not require routine laboratory monitoring and therefore the risk of nonadherence remaining undetected and without any corrective attempts must be recognized. Persistence with the NOACs and VKA was quite comparable in the phase III trials, whereas a postmarketing study demonstrated better persistence with dabigatran than with warfarin. Preliminary studies on adherence to the dabigatran regimen have shown poor adherence in 12 to 27%, and also for this drug such behavior seems associated with an unfavorable outcome. There is uncertainty about the best methods to evaluate adherence. Studies on the adherence are needed for all the NOACs, for different clinical settings and patient populations. A combination of strategies should probably be used to achieve the best possible adherence, including patient education and some form of automatic reminders.
    Seminars in Thrombosis and Hemostasis 11/2014;
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    ABSTRACT: Tissue factor pathway inhibitor (TFPI) is the major physiological regulator of tissue factor (TF)-induced blood coagulation. TFPI inhibits the TF-activated factor VII (FVIIa) complex in an activated factor X (FXa)-dependent manner, helping to control thrombin generation and ultimately fibrin formation. The importance of TFPI is demonstrated in models of hemophilia where lower levels of FVIII or FIX are insufficient to overcome its inhibitory effect, resulting in a bleeding phenotype. There are two major isoforms in vivo; TFPIα contains three Kunitz-type inhibitory domains (designated K1, K2, and K3), is secreted by endothelial cells and requires protein S to enhance its anticoagulant activity. In contrast, TFPIβ contains only the K1 and K2 domains, but it is attached to the endothelial surface via a glycosylphosphatidylinositol anchor. This review will initially provide a brief history of the major discoveries related to TFPI, and then discuss new insights into the physiology of TFPI, including updates on its association with protein S and FV, as well as the current understanding of its association with disease.
    Seminars in Thrombosis and Hemostasis 11/2014;
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    ABSTRACT: The differential diagnosis of thrombotic microangiopathy (TMA) has become clearer following the establishment of the relationships between (1) diarrhea-associated hemolytic uremic syndrome (HUS) and Shiga toxin-producing Escherichia coli-HUS (STEC-HUS), (2) a markedly reduced ADAMTS-13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) level and typical thrombotic thrombocytopenic purpura (TTP), and (3) abnormalities in the complement regulatory system and atypical HUS (aHUS). These TMAs include typical TTP, other forms of TMA, STEC-HUS, and aHUS. The pathological mechanisms of TMA still overlap among several forms of TMA. With respect to the management of TMA, the use of plasma exchange (PE) for typical TTP, additional steroid therapy for TMA and rituximab for typical TTP with a high titer of the inhibitor of ADAMTS-13, as well as eculizumab for aHUS, have also been established. Although several issues remain in the pathophysiology and management of TMA, new findings will hopefully resolve these problems in the near future.
    Seminars in Thrombosis and Hemostasis 11/2014;
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    ABSTRACT: Disseminated intravascular coagulation (DIC) is a syndrome characterized by systemic intravascular activation of coagulation, leading to a widespread deposition of fibrin in the circulation. There is ample experimental and pathological evidence that the fibrin deposition contributes to multiple organ failure. The massive and ongoing activation of coagulation may result in depletion of platelets and coagulation factors, which may cause bleeding (consumption coagulopathy). The syndrome of DIC is well known in the medical literature for centuries, although a more precise description of the underlying mechanisms had to await the 20th century. Initial ideas on a role of the contact activation system as the primary trigger for the systemic activation of coagulation as well as a presumed hyperfibrinolytic response in DIC have been found to be misconceptions. Experimental and clinical evidence now indicate that the initiation of coagulation in DIC is caused by tissue factor expression, which in combination with downregulated physiological anticoagulant pathways and impaired fibrinolysis leads to widespread fibrin deposition. In addition, an extensive bidirectional interaction between coagulation and inflammation may further contribute to the pathogenesis of DIC.
    Seminars in Thrombosis and Hemostasis 11/2014;
  • Seminars in Thrombosis and Hemostasis 10/2014;
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    ABSTRACT: The antiphospholipid syndrome (APS) is characterized by venous or arterial thrombosis and/or pregnancy morbidity in patients with persistent presence of antiphospholipid antibodies (aPL). Patients who are diagnosed with APS are identified to have a high risk of recurrent thrombosis, which can occur despite anticoagulant therapy. The optimal type, intensity, and duration of anticoagulant therapy for the treatment of APS remain controversial issues, particularly for arterial thrombosis and recurrent thrombosis. Patients with persistently positive testing for lupus anticoagulant and elevated levels of anticardiolipin antibodies and anti-β2 glycoprotein I antibodies-known as triple positivity-appear to be at increased risk for thrombosis compared with patients who test positive for a single aPL. Recognizing that patients with APS may potentially have different thrombotic risk profiles may assist clinicians in assessing the risks, benefits, and optimal duration of anticoagulation. Future studies that delineate thrombotic risk in APS and evaluate current and novel anticoagulants as well as nonanticoagulant therapies are required.
    Seminars in Thrombosis and Hemostasis 10/2014;