Journal of Thrombosis and Thrombolysis (J THROMB THROMBOLYS )

Publisher: Springer Verlag

Description

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.

  • Impact factor
    1.99
    Show impact factor history
     
    Impact factor
  • 5-year impact
    1.70
  • Cited half-life
    4.00
  • Immediacy index
    0.30
  • Eigenfactor
    0.01
  • Article influence
    0.49
  • Website
    Journal of Thrombosis and Thrombolysis website
  • Other titles
    Journal of thrombosis and thrombolysis (Online)
  • ISSN
    0929-5305
  • OCLC
    41973481
  • Material type
    Document, Periodical, Internet resource
  • Document type
    Internet Resource, Computer File, Journal / Magazine / Newspaper

Publisher details

Springer Verlag

  • Pre-print
    • Author can archive a pre-print version
  • Post-print
    • Author can archive a post-print version
  • Conditions
    • Authors own final version only can be archived
    • Publisher's version/PDF cannot be used
    • On author's website or institutional repository
    • On funders designated website/repository after 12 months at the funders request or as a result of legal obligation
    • Published source must be acknowledged
    • Must link to publisher version
    • Set phrase to accompany link to published version (The original publication is available at www.springerlink.com)
    • Articles in some journals can be made Open Access on payment of additional charge
  • Classification
    ​ green

Publications in this journal

  • Journal of Thrombosis and Thrombolysis 09/2014;
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    ABSTRACT: Oral anticoagulation (OAC) with either new oral anticoagulants (NOACs) or Vitamin-K antagonists (VKAs) is recommended by guidelines for patients with atrial fibrillation (AF) and a moderate to high risk of stroke. Based on a claims-based data set the aim of this study was to quantify the stroke-risk dependent OAC utilization profile of German AF patients and possible causes of OAC under-use. Our claims-based data set was derived from two German statutory health insurance funds for the years 2007-2010. All prevalent AF-patients in the period 2007-2009 were included. The OAC-need in 2010 was assumed whenever a CHADS2- or CHA2DS2-VASC-score was >1 and no factor that disfavored OAC use existed. Causes of OAC under-use were analyzed using multivariate logistic regression. 108,632 AF-prevalent patients met the inclusion criteria. Average age was 75.43 years, average CHA2DS2-VASc-score was 4.38. OAC should have been recommended for 56.1/62.9 % of the patients (regarding factors disfavouring VKA/NOAC use). For 38.88/39.20 % of the patient-days in 2010 we could not observe any coverage by anticoagulants. Dementia of patients (OR 2.656) and general prescription patterns of the treating physician (OR 1.633) were the most important factors increasing the risk of OAC under-use. Patients who had consulted a cardiologist had a lower risk of being under-treated with OAC (OR 0.459). OAC under-use still seems to be one of the major challenges in the real-life treatment of AF patients. Our study confirms that both patient/disease characteristics and treatment environment/general prescribing behaviour of physicians may explain the OAC under-use in AF patients.
    Journal of Thrombosis and Thrombolysis 09/2014;
  • Journal of Thrombosis and Thrombolysis 09/2014;
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    ABSTRACT: Anticoagulation (AC) is effective in reducing thromboembolic events for individuals with atrial fibrillation (AF) or mechanical heart valve (MHV), but maintaining patients in target range for international normalized ratio (INR) can be difficult. Evidence suggests increasing INR testing frequency can improve time in target range (TTR), but this can be impractical with in-clinic testing. The objective of this study was to test the hypothesis that more frequent patient-self testing (PST) via home monitoring increases TTR. This planned substudy was conducted as part of The Home INR Study, a randomized controlled trial of in-clinic INR testing every 4 weeks versus PST at three different intervals. The setting for this study was 6 VA centers across the United States. 1,029 candidates with AF or MHV were trained and tested for competency using ProTime INR meters; 787 patients were deemed competent and, after second consent, randomized across four arms: high quality AC management (HQACM) in a dedicated clinic, with venous INR testing once every 4 weeks; and telephone monitored PST once every 4 weeks; weekly; and twice weekly. The primary endpoint was TTR at 1-year follow-up. The secondary endpoints were: major bleed, stroke and death, and quality of life. Results showed that TTR increased as testing frequency increased (59.9 ± 16.7 %, 63.3 ± 14.3 %, and 66.8 ± 13.2 % [mean ± SD] for the groups that underwent PST every 4 weeks, weekly and twice weekly, respectively). The proportion of poorly managed patients (i.e., TTR <50 %) was significantly lower for groups that underwent PST versus HQACM, and the proportion decreased as testing frequency increased. Patients and their care providers were unblinded given the nature of PST and HQACM. In conclusion, more frequent PST improved TTR and reduced the proportion of poorly managed patients.
    Journal of Thrombosis and Thrombolysis 09/2014;
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    ABSTRACT: In randomized control trials and meta-analyses in patients with acute MI undergoing PCI, the radial artery (RA) approach compared to the femoral artery (FA) approach has shown to safely reduce access site related bleeding, length of hospitalization, and major adverse cardiac event (MACE) rates. However, these studies have excluded patients with cardiogenic shock. A systematic search was conducted to retrieve studies that investigated the safety of RA to FA PCI in patients with AMI and cardiogenic shock. Primary outcomes of interest was the pooled relative risk ratio (RR) of access site related bleeding. Secondary outcomes included (i) 30-day all cause mortality, (ii) major bleeding, (iii) final TIMI 3 flow, (iv) fluoroscopy time, and (v) amount of contrast volume administered. 6 observational studies with 7,753 patients met inclusion; 5,347 (69 %) with STEMI, 2,406 (31 %) with non-STEMI. In comparison of RA to FA PCI, there was less access site related bleeding (relative risk (RR) 0.11, p = 0.001), less 30-day mortality (RR 0.65, p = 0.0 < 0.001), and less major bleeding (RR of 0.46 p < 0.0001). There was no significant difference in final TIMI 3 flow (p = 0.27), fluoroscopy time (p = 0.95), and contrast volume administered (p = 0.59). In conclution, despite its limitations, our analysis demonstrates an association towards lower adverse events in the RA PCI group. Although we believe that the choice of access site in a high-risk setting should be at the operator discretion, if technically feasible, the RA appears to be a reasonable vascular access approach in high-risk patients in cardiogenic shock.
    Journal of Thrombosis and Thrombolysis 09/2014;
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    ABSTRACT: We present a case of a patient with calcific mitral valve stenosis and plasmatic hypercoagulability. Using thrombelastography, the patient was determined to have an abnormally large velocity of plasma thrombus growth and strength with reduced vulnerability to lysis. Critically, increased carboxyhemoglobin concentration (2.4 %) was present, likely secondary to hemolysis from mitral stenosis and engagement of systemic heme oxygenase. It was determined that the patient's plasmatic hypercoagulability was in part due to carboxyhemefibrinogen formation and iron-enhancement of coagulation via two thrombelastographic methods. In conclusion, future investigation of the involvement of both carbon monoxide and iron mediated hypercoagulability in the setting of stenotic valve disease is warranted.
    Journal of Thrombosis and Thrombolysis 08/2014;
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    ABSTRACT: Atrial fibrillation (AF) represents the most common cardiac arrhythmia and chronic oral anticoagulation (OAC) is the cornerstone therapy to prevent cerebrovascular events among those having high thromboembolic risk. However, 20-30% of patients with AF have co-existing coronary artery disease (CAD). Importantly, since the prevalence of both AF and CAD increase with age, management of these patients has become an emerging clinical problem with the ever growing elderly population. In particular, many of these patients may develop an acute coronary syndrome (ACS) or require percutaneous coronary intervention (PCI), leading to the concomitant use of dual antiplatelet therapy (DAPT) including aspirin and a P2Y12 receptor inhibitor in addition to OAC, also known as triple antithrombotic therapy (TAT). However, TAT comes at the expense of an increased risk of bleeding complications. This viewpoint focuses on the current evidence of treatment, areas of unmet needs and future perspectives in the management of these high-risk patients.
    Journal of Thrombosis and Thrombolysis 08/2014;
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    ABSTRACT: Thromboelastography (TEG) measures the effects of antithrombotic agents by assessing global functional clotting status by evaluating the viscoelastic properties of in vitro clot formation. Recently, rapid TEG (r-TEG), which uses tissue factor in addition to standard kaolin to accelerate activation of the clotting cascade, has been proposed to obtain more immediate results. The correlation between results of TEG or r-TEG with international normalized ratio (INR) in patients on vitamin K antagonist (VKA) therapy has not been explored and represents the aim of this study. Patients on chronic therapy with VKAs (n = 100) were included in an observational prospective pharmacodynamic study. The correlation between TEG parameters, in particular markers of thrombus generation [Reaction time (R), maximum rate of thrombus generation (MRTG), and time to maximum rate of thrombus generation (TMRTG)], and INR values as well as the concordance between these parameters and therapeutic INR ranges were evaluated. In addition, in a subgroup of subjects (n = 17), the correlation of r-TEG parameters with TEG parameters and INR values was also assessed. No correlation was found between INR and TEG parameters of thrombus generation, in particular between INR and R (r = 0.189, p = 0.06), MRTG (r = -0.027, p = 0.79), and TMRTG (r = 0.188, p = 0.06). Further, no concordance was found between these parameters and recommended INR ranges. Significant Spearman correlations were found between INR and activated clotting time (rS = 0.546, p < 0.001), r-R (rS = 0.572, p = 0.017), and r-TMRTG (rS = 0.510, p = 0.037), but not r-MRTG (rS = 0.131, p = 0.617). Results were obtained in 24 ± 6 versus 12 ± 4 min with TEG and r-TEG, respectively (p < 0.001). In patients on chronic VKA therapy, TEG is not a useful tool to evaluate VKA anticoagulant effect, compared with standard INR measurements. However, r-TEG parameters of thrombus generation correlate with INR levels, suggesting a possible role of this assay for measuring more expeditiously anticoagulant treatment effects.
    Journal of Thrombosis and Thrombolysis 08/2014;
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    ABSTRACT: Heparin induced thrombocytopenia (HIT) is a pro-thrombotic and potentially fatal complication of heparin therapy. Its diagnosis rests on high clinical probability and the laboratory demonstration of anti-PF4/heparin antibodies. The high prevalence of thrombocytopenia in hospitalized patients and the high sensitivity but low specificity of immunoassays for HIT antibodies can lead to over-testing and over-diagnosis. We conducted a study to review HIT screening practices in a tertiary care setting. We reviewed 63 consecutive patients undergoing testing for anti-PF4/heparin antibodies over 3 months. Pre-test probability for HIT was calculated using the 4T score. Sixty three patients underwent testing for anti-PF4/heparin antibodies. Twenty one had been admitted for cardiovascular surgery, 5 for other surgery and 35 for non-surgical indications. Twenty nine patients (46 %) had low pre- test probability, twenty three (36.5 %) had intermediate probability, and eleven (17.4 %) had high pre-test probability of having HIT. Anti-PF4/heparin ELISA was positive in 8 of 63 patients. SRA was ordered for 16 patients and was positive in 5. Only five patients were diagnosed and treated for HIT. Over-testing for HIT is highly prevalent in a tertiary care setting. This increases cost and exposes patients to expensive anti-coagulation with its attendant risk of hemorrhage. The 4Ts score has been shown to have high sensitivity and may be used to rule out HIT in most situations, although its utility depends on subjective analysis. Consistently applying this in practice could minimize over-testing and facilitate safer, cost-effective care.
    Journal of Thrombosis and Thrombolysis 08/2014;
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    ABSTRACT: Liver cirrhosis, myeloproliferative disorders (MPDs) and prothrombotic mutations are aetiologic factors for portal vein thrombosis (PVT). The role and frequency of thrombophilic genetic risk factors in cirrhotic patients is not well established. In this case-control study, we investigated the frequency of Janus kinase 2 (JAK2) (JAK2 V617F), Factor V Leiden (FVL G1691A), and Prothrombin (G20210A) mutations in cirrhotic patients with PVT (LCi+/PVT+ group, n = 21) in comparison with two control collectives (cirrhotic patients without PVT, LCi+/PVT- group, n = 43; PVT patients without liver cirrhosis, LCi-/PVT+ group, n = 29). In the LCi+/PVT+ group, JAK2 V617F was present in 2/21 patients (10 %; p = 0.104 compared to LCi+/PVT-; p = 0.092 compared to LCi-/PVT+), whereas 0/43 LCi+/PVT- patients (0 %; p < 0.001 compared to LCi-/PVT+) and 9/29 LCi-/PVT+ patients (31 %) harboured this mutation. The FVL G1691A mutation was identified in 1/21 patients (5 %) in the LCi+/PVT+ group, in 5/43 patients (12 %) in the LCi+/PVT- group, and in 2/29 patients (7 %) in the LCi-/PVT+ group. The Prothrombin G20210A mutation was present in 0/21 LCi+/PVT+ patients (0 %), in 1/43 LCi+/PVT- patients (2 %), and in 4/29 patients (14 %) in the LCi-/PVT+ group. This study provides evidence that a relevant proportion of cirrhotic patients with PVT harbours a JAK2 V617F mutation.
    Journal of Thrombosis and Thrombolysis 08/2014;
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    ABSTRACT: Transcatheter aortic valve replacement (TAVR) has been emerged as a promising alternative for the management of patients with severe AS who otherwise are deemed inappropriate candidates for surgery. Post procedural thromboembolic events and risk of bleeding continue to be a significant challenge in managing patients who underwent TAVR. This article systematically reviews the evidence, current guidelines and upcoming studies investigating antithrombotic therapy before, during and after TAVR.
    Journal of Thrombosis and Thrombolysis 08/2014;
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    ABSTRACT: Individual variability in the response to aspirin, has been established by various platelet function assays, however, the clinical relevance of aspirin resistance (AR) in patients undergoing coronary artery bypass grafting (CABG) has to be evaluated. Our working group conducted a randomized controlled trial (NCT01159639) with the aim to assess impact of dual antiplatelet therapy (APT) on outcomes among patients with AR following CABG. Patients that were aspirin resistant on fourth postoperative day (POD 4) were randomly assigned to receive either dual APT with clopidogrel (75 mg) plus aspirin (300 mg)-intervention arm or monotherapy with aspirin (300 mg)-control arm. This exploratory analysis compares clinical outcomes between aspirin resistant patients allocated to control arm and patients that have had adequate platelet inhibitory response to aspirin at POD 4. Both groups were treated with 300 mg of aspirin per day following surgery. We sought to evaluate the impact of early postoperative AR on outcomes among patients following CABG. Exploratory analysis included a total number of 325 patients. Of those, 215 patients with adequate response to aspirin and 110 patients with AR allocated to aspirin monotherapy following randomization protocol. The primary efficacy end point (MACCEs-major adverse cardiac and cardiovascular events) occurred in 10 and 6 % of patients with AR and with adequate aspirin response, respectively (p = 0.27). Non-significant differences were observed in bleeding events occurrence. Subgroup analysis of the primary end point revealed that aspirin resistant patients with BMI > 30 kg/m2 tend to have a higher occurrence of MACCEs 18 versus 5 % (relative risk 0.44 [95 % CI 0.16-1.16]; p = 0.05). This exploratory analysis did not reveal significant impact of aspirin resistance on outcomes among patients undergoing CABG. Further, sufficiently powered studies are needed in order to evaluate clinical relevance of AR in patients undergoing CABG.
    Journal of Thrombosis and Thrombolysis 08/2014;
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    ABSTRACT: Leukocytes have been involved in the pathogenesis of atherosclerosis, and recent attention has been raised on eosinophils, that have been claimed for a wide number of cardiovascular pathologies, affecting endocardium, myocardium and vascular walls. However, few data have been reported so far on the relationship between absolute eosinophils count (AEC) and the prevalence and extent of coronary artery disease (CAD), that was the aim of present study. Consecutive patients undergoing non-urgent coronary angiography were included. Haematological parameters were measured at admission. Significant CAD was defined as at least 1 vessel stenosis >50 %, while severe CAD as left main and/or trivessel disease, as evaluated by Quantitative Coronary Angiography. Our population is represented by 3,742 patients, divided according to tertiles values of AEC (≤0.1; 0.1-0.2; >0.2 × 10(3)/µl). Higher eosinophils values were significantly associated to male gender, main established cardiovascular risk factors, previous percutaneous or surgical coronary revascularization, antihypertensive and antiplatelet therapy at admission but inversely with acute presentation. Higher AEC was directly related with platelets count (p < 0.001), haemoglobin levels (p = 0.02), white blood cells count (p = 0.02), higher serum creatinine (p < 0.001), triglycerides (p < 0.001) and glycosylated haemoglobin (p < 0.001), while inversely with HDL cholesterol (p < 0.001). AEC was associated with multivessel disease (p = 0.03), chronic occlusions (p = 0.01), in-stent restenosis (p = 0.002), while inversely with the presence of intracoronary thrombus (p < 0.001). A significant relationship was found between AEC and the prevalence of coronary artery disease (p = 0.049), but not for the extent of more severe LM/trivessel CAD (p = 0.31). At multivariate analysis no independent role of eosinophils was found for CAD (adjusted OR [95 % CI] = 1.02 [0.91-1.15], p = 0.70), or severe CAD (adjusted OR [95 % CI] = 0.99 [0.89-1.1], p = 0.9), even when considering separately acute and elective patients. In conclusion, among patients undergoing coronary angiography, higher eosinophils levels are not independently associated with the prevalence and extent of coronary artery disease, but appear confounded by their link with major cardiovascular risk factors.
    Journal of Thrombosis and Thrombolysis 07/2014;
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    ABSTRACT: Current stroke treatment guidelines exclude unknown onset stroke (UOS) patients from thrombolytic therapy even though several studies have reported significant treatment efficacy and safety. We performed a meta-analysis of relevant studies retrieved by systematic searches of the PubMed, Embase, and Cochrane databases up to December 31, 2013. Dichotomized modified Rankin Scale (mRS) scores 0-1 at 90 days, mRS 0-2 at 90 days, overall mortality, and symptomatic intracranial hemorrhage (sICH) incidence were collected as primary outcome measures. Fixed effects meta-analytical models were used, and between-study heterogeneity was assessed. Eleven studies encompassing 1,832 patients were included. In case-control studies of UOS patients, thrombolysis was associated with a significant increase in the proportion of patients with mRS scores of 0-1 (OR 2.37; 95 % CI 1.20-4.69; P = 0.013) and 0-2 (OR 2.03; 95 % CI 1.26-3.30; P = 0.004) without increased mortality or sICH incidence. In studies comparing thrombolysis-treated UOS to thrombolysis-treated known onset stroke, however, fewer UOS patients had mRS scores of 0-1 (OR 0.70; 95 % CI 0.51-0.97; P = 0.033) with no change in mortality, sICH incidence, or patients with mRS of 0-2. Subgroup analysis based on imaging criteria and time window of thrombolysis indicated that UOS patients treated within 3 h after first found abnormal and those with early ischemic changes restricted to <1/3 of the middle cerebral artery territory gained more benefit from thrombolysis treatment than the whole UOS population. Randomized controlled trials are warranted to confirm the efficacy of thrombolysis in this UOS subgroup.
    Journal of Thrombosis and Thrombolysis 07/2014;
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    ABSTRACT: Recombinant activated factor VII (rFVIIa) was initially developed to treat bleeding episodes in patients with congenital hemophilia and inhibitors. Due to the initial success in this clinical setting, its use has been extended to other coagulopathies characterized by impaired thrombin generation, i.e. acquired hemophilia, inherited factor VII deficiency and Glanzmann's thrombasthenia, for which it is currently licensed. Extensive research in the last decade has increased our knowledge of the mechanisms utilized by rFVIIa to restore normal hemostasis. This paper reviews current understanding of the mechanisms of action of rFVIIa before summarizing the clinical experience, in terms of safety and efficacy, to date in its licensed indications.
    Journal of Thrombosis and Thrombolysis 07/2014;
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    ABSTRACT: ABO dependent variation in von Willebrand factor (vWf) and procoagulant factor VIII (FVIII) is a plausible mechanism for modulating perioperative hemostasis and bleeding. Group AB has the highest and group O the lowest vWf and FVIII levels. Therefore, we tested the hypothesis that ABO blood group is associated with perioperative transfusion and subsequent survival after coronary revascularization. This retrospective study combined demographic, operative, and transfusion data, including follow-up for a median of 2,096 days, for consecutive aortocoronary bypass (CABG) and CABG/valve procedures from 1996-2009 at a tertiary referral University Heart Center. Between group differences were compared by a Kruskall Wallis test, and hazard ratios [95 % confidence intervals] are reported for mortality risk-adjusted Cox proportional hazards regression analysis. From 15,454 patients, follow-up records were available for 13,627 patients: 6,413 group O, 5,248 group A, 1,454 group B, and 435 group AB. Packed red blood cells were the most commonly transfused blood product (3 [0-5] units), while group AB received 2 [0-5] units (Kruskall Wallis Chi squared value for between group differences = 8.2; p = 0.04). Group AB favored improved long-term, postoperative survival (Hazard ratio = 0.82 [95 %CI 0.68-0.98]; p = 0.03), which became evident approximately a year after surgery. In conclusion, the procoagulant phenotype of blood group AB is associated with fewer transfusions and improved late survival after cardiac surgery. Whether this finding is related to fewer perioperative transfusions, a reduction in later bleeding or other mechanisms remains speculative.
    Journal of Thrombosis and Thrombolysis 06/2014;
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    ABSTRACT: Streptokinase (SK) is an extracellular enzyme secreted by various strains of β-hemolytic Streptococci. The main focus of the current study is to evaluate the in vitro thrombolytic activity of purified SK extracted from Streptococcus equinus VIT_VB2 (Accession no. JX406835) isolated from milk sample. The growth rate of S. equinus VIT_VB2 strain was studied with pH and biomass content which has positive significant effect on enzyme yield. A temperature of 10 °C and pH of 6 was found to be optimum for maximum SK activity. The specific activity of the purified SK produced by VIT_VB2 strain was found to be 6,585 IU mg(-1). The molecular mass of the enzyme was determined as 47 kDa by SDS-PAGE. In vitro thrombolytic activity of purified SK was determined using synthetic chromogenic substrate S-2251, the activity of the purified enzyme was found to be 6,330 ± 2.2 IU. The purity of SK was compared with standard SK by HPLC. This is the first report which reveals the SK activity of S. equinus isolated from milk sample.
    Journal of Thrombosis and Thrombolysis 06/2014;
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    ABSTRACT: This is a case report of catastrophic antiphospholipid syndrome (APLS) involving the rare manifestation of pulmonary hemorrhage. This rare variant of APLS is frequently life threatening despite medical therapy. The pathogenesis of pulmonary hemorrhage in catastrophic APLS remains incompletely understood. The optimal approach to managing pulmonary hemorrhage in the setting of catastrophic APLS is still unclear, however this case report demonstrates the success of combination therapy with anticoagulation, corticosteroids and plasma exchange.
    Journal of Thrombosis and Thrombolysis 06/2014;
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    ABSTRACT: Currently, there is a lack of consensus among guidelines for the postdischarge treatment of patients presenting with acute coronary syndrome (ACS) who have a long-term indication for anticoagulation. We conducted a systematic review comparing the safety and effectiveness of dual antiplatelet therapy (DAPT) and triple therapy (TT; defined as DAPT plus an oral anticoagulant) in patients with ACS and a long-term indication for anticoagulation. We searched for clinical studies in MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews published between January 1995 and September 2013. Each investigator screened and abstracted data, assessed applicability and quality, and graded the strength of evidence. Meta-analysis of direct comparison was performed when outcomes and follow-up periods were comparable. Fourteen observational studies were identified that contained comparative effectiveness data on DAPT versus TT. No difference in the odds of mortality (OR 1.04, 95 % CI 0.59–1.83) or stroke (OR 1.01, 95 % CI 0.38–2.67) at 1–5 years was found between TT and DAPT. Major bleeding at 1–5 years (OR 1.46, 95 % CI 1.07–2.00) and nonfatal MI at 1–5 years (OR 1.85, 95 % CI 1.13–3.02) occurred more frequently in patients receiving TT. The results of this systematic review demonstrate that treatment with TT was associated with increased rates of nonfatal MI and major bleeding when compared with treatment with DAPT in the postdischarge management of ACS patients with an indication for oral anticoagulation. Until results of ongoing randomized trials assessing antithrombotic therapies define optimal management strategies, the current analysis suggests using caution when prescribing TT to these patients.
    Journal of Thrombosis and Thrombolysis 06/2014;
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    ABSTRACT: The REG2 Anticoagulation System consists of pegnivacogin, a subcutaneously administered aptamer factor IXa inhibitor, and its intravenous active control agent, anivamersen. Its effect on thrombin generation is unknown. A prospectively designed thrombin generation study was conducted within the phase 1 ascending dose study of REG2 to assess the effect of REG2 on thrombin generation kinetics. A total of 32 healthy volunteers were recruited into four cohorts of ascending dose pegnivacogin for the phase 1 study. In this pre-specified substudy, blood samples were drawn in the presence or absence of corn trypsin inhibitor at specified times within each dosing cohort. Thrombin generation was initiated with tissue factor and thrombin generation kinetics were measured using the Calibrated Automated Thrombogram (CAT). REG2 attenuated thrombin generation in a dose-dependent manner. All parameters of the CAT assay, except for lag time, showed a dose and concentration-dependent response to pegnivacogin [time to peak thrombin generation (PTm), endogenous thrombin potential, peak thrombin generation, and velocity index (VIx)]. Reversal of the effect of pegnivacogin with anivamersen demonstrated restoration of thrombin generation without rebound effect. This first-in-human study of the effect of the REG2 Anticoagulation System on thrombin generation demonstrates concentration-dependent suppression of thrombin generation that is reversible without rebound effect, as measured by the CAT assay.
    Journal of Thrombosis and Thrombolysis 06/2014;

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