Journal of Thrombosis and Thrombolysis (J Thromb Thrombolysis )

Publisher: LINK (Springer), Springer Verlag


The Journal of Thrombosis and Thrombolysis is a long-awaited resource for contemporary cardiologists hematologists and clinician-scientists actively involved in treatment decisions and clinical investigation of thrombotic disorders involving the cardiovascular and cerebrovascular systems. Its principal focus centers on the pathobiology of thrombosis and the use of anticoagulants platelet antagonists and thrombolytic agents in scientific investigation and patient care. The journal publishes original work that interlinks basic scienctific principles with clinical investigation thus creating a unique forum for interdisciplinary dialogue. Published works will advocate the development of solid platforms for planned clinical research and precise clinically-applicable benchwork. The Journal of Thrombosis and Thrombolysis 's comprehensive and interdisciplinary design will expand the reader's knowledge base and provide important insights for the most rapidly growing field in medicine. The journal seeks original manuscripts devoted to laboratory investigation and clinical studies. State-of-the-art reviews and editorials will be summoned by invitation. The journal will closely follow new trends on the cutting edge of the field and highlight drugs in the early stages of development which may warrant testing in the clinical arena. Updates of major national and international clinical trials will also be provided as will a forum of guidelines for interpreting the results of these trials from a patient care perspective. The Journal will publish an ongoing educational series of topics applicable to clinician scientists that will include such topics as: 'Seminars in Thrombosis Thromboysis and Vascular Biology' and a 6-part series on 'Hematology for the Cardiologist'. Manuscripts submitted must not be under consideration by an other journal and should not have been published elsewhere in similar form. All articles will be refereed by two qualified referees. All clinical trials being considered for publication will also be reviewed by a statistician. A response will be provided within four weeks of receipt.

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    Journal of Thrombosis and Thrombolysis website
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    Journal of thrombosis and thrombolysis (En ligne)
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    Internet Resource, Journal / Magazine / Newspaper

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Springer Verlag

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Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: Platelet apoptosis occurs commonly under various conditions such as physical and chemical stimuli. Acute coronary syndrome (ACS), one of most important cardiovascular and cerebrovascular diseases, severely threats people's health and is usually accompanied with various complications especially bleeding. There might be platelet apoptosis in ACS, which might be responsible for the complication of bleeding. The objective of the present study was to explore whether there were apoptotic platelets in ACS patients. Vein blood was drawn from eleven ACS patients and eleven health people. Platelet-rich plasma was prepared and subjected to apoptotic events analysis including increased expression of pro-apoptotic proteins and decreased expression of anti-apoptotic proteins, exposure of phosphatidylserine (PS), mitochondrial inner membrane potential depolarization and caspase-3 activation by Western blot and flow cytometry. In addition, washed platelets from the normal people were prepared and treated with the platelet-poor plasma (PPP) of the ACS patients, and were further examined apoptotic cascades. Paired Student's t test was used in the data comparisons. There were more platelets with depolarized mitochondrial inner membrane potential in the ACS patients than those of the health donors. Levels of Bax and Bak increased, while expression of Bcl-2 and Bcl-XL decreased in platelets from ACS patients. Caspase-3 activation was observed in platelets from the patients with ACS. Interestingly, there were significant differences in PS exposure between the platelets from the ACS patients and the normal controls. Furthermore, apoptotic events were observed in the normal platelets incubated with PPP from the ACS patients. In addition, pretreatment of healthy platelets with anti-oxidants N-acetyl cysteine (NAC) or dithiothreitol (DTT) significantly reduced ACS patients-derived PPP-induced platelet apoptosis. Platelets from the ACS patients are incurred apoptosis. Antioxidants NAC or DTT can reduce ACS patients-derived PPP-induced platelet apoptosis in vitro.
    Journal of Thrombosis and Thrombolysis 12/2014;
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    ABSTRACT: The aim of this study was the identification of the optimal cutoff value of high residual platelet reactivity (HRPR) assessed by light transmission aggregometry (LTA) in the responsiveness to clopidogrel and stent thrombosis 2-acute coronary syndrome (RECLOSE 2-ACS) patient cohort to discriminate patients with and without major adverse cardiac events (MACE) and cardiac death at 2 years. The RECLOSE 2-ACS study included 1,789 patients with ACS who underwent LTA after clopidogrel loading. A post hoc cutoff value for HRPR was defined with the ROC curve and the Youden index and compared with the protocol-defined cutoff of 70 %. By ROC analysis, 63 % resulted the optimal cutoff value to predict both MACE and cardiac death at 2 years follow-up. A significant sensitivity improvement for the ROC-based cutoff value was noted (p < 0.001), at the price of lower specificity and predictive accuracy. The latter were 81 % for MACE and 85 % for cardiac death with the 70 % cutoff, while the respective figures were 73 and 75 % with the 63 % cutoff. The areas under the curve were virtually identical with the 70 and 63 % cutoffs both for MACE (0.71) and cardiac death (0.79). A residual platelet reactivity cutoff of 70 % by LTA, compared to the ROC-based cutoff of 63 %, allows for the identification of a subset of patients at very high risk of adverse ischemic events, making LTA-ADP test more acceptable in clinical practice for the identification of subjects at risk than other platelet function assays with broader definitions of HRPR.
    Journal of Thrombosis and Thrombolysis 12/2014;
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    ABSTRACT: Assessment of thromboembolic risk is crucial for proper management of atrial fibrillation (AF) patients. Currently used risk score base only on scarce clinical data and do not take into consideration parameters including echocardiographic findings. The aim of this study was to evaluate if left atrium (LA) enlargement is associated with higher thromboembolic risk assessed by CHADS2 and CHA2DS2-VASc scores in a cohort of unselected non-valvular AF patients. Data from 582 AF hospitalizations occurring between November 2012 and January 2014 were analyzed. All patients underwent a standard transthoracic echocardiography and had their thromboembolic risk assessed in both CHADS2 and CHA2DS2-VASc scores. In 494 enrolled patients (48.5 % male; mean age 73.4 ± 11.5 years) AF was classified as paroxysmal in 233 (47.3 %), as persistent in 109 (22.1 %), and as permanent in 151 (30.6 %) patients. LA was enlarged in 426 (86.2 %) patients. Enlargement was classified as mild in 99 (20.0 %) patients, as moderate in 130 (26.3 %) patients, and as severe in 196 (39.7 %) patients. Patients with enlarged LA had higher mean CHADS2 score (2.0 ± 1.5 vs. 2.6 ± 1.3; p = 0.0005) and CHA2DS2-VASc (3.8 ± 2.0 vs. 4.4 ± 1.8; p = 0.02) score than patients with normal LA. The both mean scores rose along with rising LA diameter. LA enlargement is highly prevalent in AF patients. Higher thromboembolic risk assessed by both CHADS2 and CHA2DS2-VASc scores is associated with presence of LA enlargement. Echocardiographically assessed LA size may be an additional parameter useful in thromboembolic risk stratification of AF patients.
    Journal of Thrombosis and Thrombolysis 12/2014;
  • Journal of Thrombosis and Thrombolysis 12/2014;
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    ABSTRACT: The leech protein hirudin is a potent natural thrombin inhibitor. Its potential as an antithrombotic agent is limited by its promotion of bleeding. We attempted to modify this profile by positioning albumin and a plasmin cleavage site on its N-terminus, in recombinant protein HSACHV3 [comprising hirudin variant 3 (HV3) fused to the C-terminus of human serum albumin (HSA) via a plasmin cleavage site (C)], Previously we showed that HSACHV3 inhibited thrombin in a plasmin-dependent manner, and that, unlike HV3, it did not increase bleeding in vivo when administered to mice. Here we tested HSACHV3 for the ability to reduce thrombosis and assist enzymatic thrombolysis in animal models. Intravenous administration of HSACHV3, but not a control protein lacking the plasmin cleavage site (HSAHV3), reduced thrombus weight by 2.1-fold in the ferric chloride-injured mouse vena cava. Similarly, thrombi formed in a rabbit jugular vein stasis model were 1.7-fold lighter in animals treated with HSACHV3 compared to those receiving HSAHV3. Administration of 60 mg/kg body weight HSACHV3 prolonged the time to occlusion in the ferric chloride-injured mouse carotid artery by threefold compared to vehicle controls, while equimolar HSAHV3 had no effect. HSACHV3 had no ability to restore flow to the murine carotid arteries occluded by ferric chloride treatment, but combining HSACHV3 (60 mg/kg) with recombinant mutant tissue plasminogen activator (TNKase) significantly reduced the time to restore patency to the artery compared to TNKase alone. Unlike unfused HV3, HSACHV3 did not increase bleeding in a mouse liver laceration model. Our results show that HSACHV3 acts as an antithrombotic agent that does not promote bleeding and which speeds the time to flow restoration when used as an adjunct to pharmacological thrombolysis in animal models.
    Journal of Thrombosis and Thrombolysis 12/2014;
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    ABSTRACT: Acute pulmonary embolism (PE) can diminish patient quality of life (QoL). The objective was to test whether treatment with tenecteplase has an independent effect on a measurement that reflects QoL in patients with submassive PE. This was a secondary analysis of an 8-center, prospective randomized controlled trial, utilizing multivariate regression to control for predefined predictors of worsened QoL including: age, active malignancy, history of PE or deep venous thrombosis (DVT), recurrent PE or DVT, chronic obstructive pulmonary disease and heart failure. QoL was measured with the physical component summary (PCS) of the SF-36. Analysis included 76 patients (37 randomized to tenecteplase, 39 to placebo). Multivariate regression yielded an equation f(8, 67), P < 0.001, with R(2) = 0.303. Obesity had the largest effect on PCS (β = -8.6, P < 0.001), with tenecteplase second (β = 4.73, P = 0.056). After controlling for all interactions, tenecteplase increased the PCS by +5.37 points (P = 0.027). In patients without any of the defined comorbidities, the coefficient on the tenecteplase variable was not significant (-0.835, P = 0.777). In patients with submassive PE, obesity had the greatest influence on QoL, followed by use of fibrinolysis. Fibrinolysis had a marginal independent effect on patient QoL after controlling for comorbidities, but was not significant in patients without comorbid conditions.
    Journal of Thrombosis and Thrombolysis 11/2014;
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    ABSTRACT: While the use of warfarin has been the cornerstone of thromboembolism prevention in patients with atrial fibrillation (AF), its limitations have led to the introduction of a new generation of direct-acting oral anticoagulants. Evidence from large phase III clinical trials, observational studies and pharmacokinetic analyses can guide clinicians to select the most effective and safest form of anticoagulation for patients with nonvalvular AF. This manuscript describes the main pharmacologic, clinical and epidemiological characteristics of each new oral anticoagulant and their use in selected clinical scenarios, including patients with: advanced age; at low or high risk of stroke; potential drug-drug interactions; on concomitant antiplatelet therapy; at high risk for acute coronary syndrome; with recent gastrointestinal bleeding; with renal impairment; and with hepatic dysfunction.
    Journal of Thrombosis and Thrombolysis 11/2014;
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    ABSTRACT: In the last decade, major advances in venous thromboembolism (VTE) prophylaxis in orthopaedic surgery have included the development of new anticoagulants that are poised to replace low molecular weight heparins (LMWHs) and improvements in operative and perioperative care that have likely led to a decline in the rates of symptomatic VTE and mortality independent of anticoagulant use. A systematic review of the literature was performed to identify phase III randomized controlled trials of VTE prevention that compared new anticoagulants (fondaparinux, rivaroxaban, dabigatran, apixaban) with LMWH (enoxaparin) in major elective orthopaedic surgery. Our aims were to obtain best estimates of the rates of patient important events (symptomatic VTE, mortality, and bleeding) in contemporary trials of VTE prevention, and to consider the implications of these contemporary rates for clinical practice and future research. Fourteen studies, which enrolled 40,285 patients, were included in the analyses. The combined median rates (ranges) for all five anticoagulants for symptomatic VTE and mortality to the end of follow-up were 0.99 % (0.15-2.58 %) and 0.26 % (0-0.92 %) respectively, whereas the median rate (range) of clinically important bleeding was 3.44 % (2.25-7.74 %). In contemporary trials of anticoagulants, the rates of symptomatic VTE and mortality are low, but the rates of clinically important post-operative bleeding remain relatively high. Based on these results, we propose that approaches that minimize bleeding without substantially reducing efficacy merit investigation, particularly if improvement in surgical and perioperative care have also resulted in falling baseline patient important VTE rates independent of anticoagulant use.
    Journal of Thrombosis and Thrombolysis 11/2014;
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    ABSTRACT: Herein we present two cases of hypereosinophilic syndrome with a unique clinical presentation. One patient showed severe systemic thrombosis with splenic rupture and the other patient showed finger gangrene with various systemic symptoms. Both patients were examined histologically, and several characteristics were noted. First, fresh or organized thrombosis with marked eosinophilic infiltration was observed in the cavity and walls of the thrombosed vessels. Second, many eosinophils showed degranulation and were positive for eosinophilic cationic protein on immunohistological examination. Third, the structures of thrombosed vessels were well preserved, which is not observed in systemic vasculitis. These patients exhibited no neoplastic features and were treated with prednisolone with excellent therapeutic results.
    Journal of Thrombosis and Thrombolysis 11/2014;
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    ABSTRACT: Micro and macrovascular complications occurring during hyperlipidemia are mostly attributed to haemostatic impairment and vascular endothelial dysfunction. Cholesteryl ester transfer protein (CETP) inhibitors have been emerged recently as promising hypocholesterolemic agents to confer protection against lipid-mediated atherosclerosis. Therefore, 10-dehydrogingerdione (DHGD), a novel CETP inhibitor isolated from ginger rhizomes, was selected as a natural product in the present study to illustrate its effect on haemostatic impairment associated with hyperlipidemia as compared to a currently used hypocholesterolemic agent, atorvastatin (ATOR). Rabbits were fed a high cholesterol diet (HCD) and divided into three groups. One group served as control group while the other groups received DHGD or ATOR. Dyslipidemic rabbits showed a significant increase in serum endothelin-1, ischemia modified albumin, plasminogen activator inhibitor-1, prothrombin fragments (1+2) and plasma fibrinogen along with a decrease of nitric oxide level in serum. Daily administration of ATOR or DHGD significantly decreased the aforementioned coagulation and ischemia biomarkers and increased serum nitric oxide. DHGD (natural) results seem to be more remarkable as compared to ATOR (synthetic).
    Journal of Thrombosis and Thrombolysis 11/2014;
  • Journal of Thrombosis and Thrombolysis 08/2014;
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    ABSTRACT: Patients with inflammatory bowel disease (IBD) have a 1.5-3.5-fold higher risk of thromboembolism when compared to the non-IBD population and the risk is much more prominent at the time of a flare. Arterial thromboembolism (ischemic stroke, focal white matter ischemia, cardiac ischemia, peripheral vascular disease and mesenteric ischemia) and venous thromboembolism (deep vein thrombosis and pulmonary embolism, cerebral venous sinus thrombosis, retinal, hepatic, portal and mesenteric vein thromboses) belong to the group of underestimated extraintestinal complications in IBD patients, which are associated with a high morbidity and mortality rate (the overall mortality is as high as 25 % per episode). Thromboembolism occurs in younger patients compared to the non-IBD population and has a high recurrence rate. Multiple risk factors are involved in the etiopathogenesis, but the acquired ones play the key role. Congenital alterations do not occur more frequently in IBD patients when compared to the non-IBD population. Standardized guidelines for the prophylaxis of thromboembolism in IBD patients are urgently needed and these should be respected in clinical practice to avoid preventable morbidity and mortality.
    Journal of Thrombosis and Thrombolysis 08/2014;
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    ABSTRACT: In stroke patients higher levels of plasma fibrinogen are associated with increased risk of unfavourable functional outcome and short-term mortality. The aim of our study was to determine the relationship between plasma fibrinogen level and long-term risk of death in ischemic stroke patients. Seven hundred thirty six patients (median age 71; 47.1 % men) admitted to the stroke unit within 24 h after stroke were included. Plasma fibrinogen level was measured on day 1 of hospitalisation. Hyperfibrinogenemia was defined as plasma fibrinogen concentration >3.5 g/L. The maximal follow-up period was 84 months. Hyperfibrinogenemia was found in 25.0 % of patients. On multivariate logistic regression analysis, after adjustment for age, stroke severity, atrial fibrillation, smoking, white blood cell count, fever, in-hospital pneumonia and hyperglycemia, hyperfibrinogenemia was associated with increased case fatality (HR 1.71, 95 % CI 1.29-2.26, P < 0.01). Hyperfibrinogenemia predicts the long-term risk of death in ischemic stroke patients.
    Journal of Thrombosis and Thrombolysis 08/2014;
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    ABSTRACT: Dabigatran, a new direct thrombin inhibitor, achieves strong anticoagulation that is more predictable than warfarin. Nevertheless, a patient on dabigatran therapy (DT) may suffer from thrombotic or bleeding events. The routine monitoring of DT is not recommended, and standard coagulation tests are not sensitive enough for the assessment of DT activity. The aim of this study was to examine the clinical usefulness of the Hemoclot(®) Thrombin Inhibitor (HTI) assay in the assessment of dabigatran plasma levels in patients with non-valvular AF. Nineteen patients (12 men, 7 women) on DT were included in this preliminary prospective observational study. Dabigatran was administrated twice daily in a two dose regimens: 150 mg (5 patients) and 110 mg (14 patients). Blood samples were taken for the assessment of trough and peak levels of dabigatran. Dabigatran concentrations were measured with the HTI assay. The average dabigatran trough level was 69.3 ± 55.5 ng/ml and the average dabigatran peak level was 112.7 ± 66.6 ng/ml. The dabigatran trough plasma concentration was in the established reference range in 15 patients and the dabigatran peak plasma concentration was in the established reference range in 9 patients, respectively. Despite the fact that the activated partial thromboplastin and thrombin times were generally changed (prolonged), these tests failed to identify the patients with too low or too high dabigatran concentrations. The study confirmed the high sensitivity of the HTI assay for the assessment of dabigatran plasma levels. When compared to standard coagulation tests, the HTI is a more suitable assay for the monitoring of patients treated with dabigatran. Monitoring of DT may be beneficial in selected patients; however, further studies will be needed for the final clarification of this issue.
    Journal of Thrombosis and Thrombolysis 08/2014;
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    ABSTRACT: The effect of obesity on the pharmacokinetics of enoxaparin is not clearly understood and traditional treatment doses in morbidly obese patients (body mass index [BMI] > 40 kg/m(2)) can lead to over anticoagulation. Our institution developed an inpatient protocol with reduced enoxaparin doses (0.75 mg/kg/dose based on actual body weight) for patients with a weight >200 kg or BMI > 40 kg/m(2). The primary objective was to determine if modified enoxaparin treatment doses would achieve therapeutic anti-Xa levels (goal range 0.6-1.0 IU/mL) in morbidly obese patients. Thirty-one patients were included in our study and had a median body weight of 138 kg (range 105-197) and a median BMI of 46.2 kg/m(2) (range 40.1-62). The initial peak anti-Xa levels were in therapeutic range in 15 of 31 patients (48 %) with an initial mean anti-Xa level of 0.92 IU/mL. Twenty-four patients (77 %) achieved therapeutic anti-Xa levels in goal range during their hospitalization, with a mean enoxaparin dose of 0.71 mg/kg. Bleeding and thrombotic events were minimal and all patients that achieved an anti-Xa level in goal range did so with a dose less than 1 mg/kg of enoxaparin.
    Journal of Thrombosis and Thrombolysis 08/2014;
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    ABSTRACT: The primary care regularly sees patients that have symptoms that could be due to thromboembolic diseases. It would be valuable to be able to rule out deep venous thrombosis or pulmonary embolism using Wells score and a negative D-dimer testing already at the primary care unit. This requires a validated D-dimer assay suitable for primary care use. We compared D-dimer results obtained with the new point of care analyzer Alere Triage(®) and the central hospital laboratory STA-R Evolution analyzer from the same patient samples (n = 102). We also calculated the total coefficient of variation (CV) for the Alere method. The two methods showed a good linear correlation (R(2) = 0.977) and a slope of 0.975. CV for the Alere D-dimer method was well below 10 %. The study shows that the Alere D-dimer assay and the central laboratory standard assay show similar results. We suggest that the Alere D-dimer assay could be used in primary care in combination with Wells score to reduce referrals to the emergency unit.
    Journal of Thrombosis and Thrombolysis 08/2014;
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    ABSTRACT: The objective of this study was to assess deep vein thrombosis and pulmonary embolism (DVT/PE) recurrence rates and resource utilization among patients with an initial DVT or PE event across multiple payer perspectives. Retrospective analyses were performed using a software tool that analyzes health plan claims to evaluate treatment patterns and resource utilization for various cardiovascular conditions. Six databases were analyzed from three payer perspectives (Commercial, Medicare, and Medicaid). Patients were ≥18 years old with a primary diagnosis of DVT or PE associated with an inpatient and/or emergency room claim, had received an antithrombotic within 7 days before or 14 days after index, and had no diagnosis of atrial fibrillation during follow-up. Outcomes were assessed over a 1 year period following index. More PE patients were hospitalized for their index event than DVT patients (42-59 % DVT and 69-86 % PE) and had longer mean length of stay (2.35-2.95 days DVT and 3.26-3.76 days PE). Recurrent event rates among PE patients (12-32 %) were higher than those for DVT patients (6-16 %) across all payers. The highest rate of recurrence was observed among the Medicaid population [23 % overall (VTE); 16 % DVT; 32 % PE]. All-cause hospitalization in the year following their VTE episode occurred in 23-67 % DVT patients and 30-68 % PE patients. Medicaid had the highest proportion of patients with hospitalizations and ER visits. Recurrent VTE events and all-cause hospitalizations are relatively common, especially for patients who had a PE, and among those in the Medicaid payer population.
    Journal of Thrombosis and Thrombolysis 07/2014;