Thrombosis and Haemostasis (THROMB HAEMOSTASIS)

Publisher: International Society on Thrombosis and Haemostasis, Schattauer

Journal description

Thrombosis and Haemostasis publishes original papers only, as well as reports, news and inside information about current research and science. In addition, it presents innovative results of scientific research which will be the practitioner's tool of tomorrow. Thrombosis and Haemostasis is read by haematologists, angiologists, cardiologists, surgeons, gynaecologists, internal specialists and laboratory physicians. Thrombosis and Haemostasis is published monthly. It is the official journal of the International Society on Thrombosis and Haemostasis (ISTH). All members of the Society receive Thrombosis and Haemostasis as part of their Society membership.

Current impact factor: 4.98

Impact Factor Rankings

2016 Impact Factor Available summer 2017
2014 / 2015 Impact Factor 4.984
2013 Impact Factor 5.76
2012 Impact Factor 6.094
2011 Impact Factor 5.044
2010 Impact Factor 4.701
2009 Impact Factor 4.451
2008 Impact Factor 3.803
2007 Impact Factor 3.501
2006 Impact Factor 2.803
2005 Impact Factor 3.056
2004 Impact Factor 3.413
2003 Impact Factor 4.95
2002 Impact Factor 4.357
2001 Impact Factor 4.91
2000 Impact Factor 4.372
1999 Impact Factor 4.983
1998 Impact Factor 3.726
1997 Impact Factor 4.582
1996 Impact Factor 4.267
1995 Impact Factor 4.464
1994 Impact Factor 4.125
1993 Impact Factor 4.352
1992 Impact Factor 4.481

Impact factor over time

Impact factor

Additional details

5-year impact 4.45
Cited half-life 8.10
Immediacy index 1.25
Eigenfactor 0.03
Article influence 1.49
Website Thrombosis & Haemostasis website
Other titles Thrombosis and haemostasis
ISSN 0340-6245
OCLC 2208259
Document type Journal / Magazine / Newspaper, Internet Resource

Publisher details


  • Pre-print
    • Author can archive a pre-print version
  • Post-print
    • Author cannot archive a post-print version
  • Restrictions
    • 12 months embargo
  • Conditions
    • On authors personal website, institutional repository or centrally organized repository
    • On a non-profit server
    • Publisher copyright and source must be acknowledged with set statement (see policy)
    • Publisher's version/PDF cannot be used
  • Classification

Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: The prognostic significance of patients presenting with pulmonary embolism (PE) and elevated International Normalised Ratio (INR) not on anticoagulant therapy has not been described. We investigated whether these patients had higher mortality compared to patients with normal INR. A retrospective study of patients admitted to a tertiary hospital with acute PE from 2000 to 2012 was undertaken, with study outcomes tracked using a state-wide death registry. Patients were excluded if they were taking anticoagulants or had inadequate documentation of their INR and medication status. Of the 1,039 patients identified, 94 (9 %) had an elevated INR (> 1.2) in the absence of anticoagulant use. These patients had higher mortality at six months follow-up (26 % vs 6 %, p< 0.001) compared to controls (INR ≤ 1.2). An INR > 1.2 at diagnosis was an independent predictor of death at six months post-PE (hazard ratio [HR] 2.9, 95 % confidence interval [CI] 1.8-4.7, p< 0.001). The addition of INR to a multivariable model that included the simplified pulmonary embolism severity index (sPESI), chest pain, and serum sodium led to a significant net reclassification improvement estimated at 8.1 %. The final model's C statistic increased significantly by 0.04 (95 % CI 0.01-0.08, p=0.03) to 0.83 compared to sPESI alone (0.79). In summary, patients presenting with acute PE and elevated INR while not on anticoagulant therapy appear to be at high risk of death. Future validation studies in independent cohorts will clarify if this novel finding can be usefully incorporated into clinical decision making in patients with acute PE.
    No preview · Article · Feb 2016 · Thrombosis and Haemostasis
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    ABSTRACT: Hospital-associated venous thromboembolism (VTE) is a leading cause of premature death and disability worldwide. Evidence-based guidelines recommend that anticoagulant thromboprophylaxis be given to hospitalised medical patients at risk of VTE, but suggest against routine use of thromboprophylaxis beyond the hospital stay. The MARINER study is a randomised, double-blind, placebo-controlled trial to evaluate the efficacy and safety of thromboprophylaxis using rivaroxaban, begun at hospital discharge and continued for 45 days, for preventing symptomatic VTE in high-risk medical patients. Eligible patients are identified using the International Medical Prevention Registry on Venous Thromboembolism (IMPROVE VTE) risk score, combined with a laboratory test, D-dimer. The rivaroxaban regimen is 10 mg once daily for patients with CrCl ≥ 50 ml/min, or 7.5 mg once daily for patients with CrCl ≥ 30 ml/min and < 50 ml/min. The primary efficacy outcome is the composite of symptomatic VTE (lower extremity deep-vein thrombosis and non-fatal pulmonary embolism) and VTE-related death. The principal safety outcome is major bleeding. A blinded clinical events committee adjudicates all suspected outcome events. The sample size is event-driven with an estimated total of 8,000 patients to acquire 161 primary outcome events. Study design features that distinguish MARINER from previous and ongoing thromboprophylaxis trials in medically ill patients are: (i) use of a validated risk assessment model (IMPROVE VTE) and D-dimer determination for identifying eligible patients at high risk of VTE, (ii) randomisation at the time of hospital discharge, (iii) a 45-day treatment period and (iv) restriction of the primary efficacy outcome to symptomatic VTE events.
    No preview · Article · Feb 2016 · Thrombosis and Haemostasis
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    ABSTRACT: Blood flow is an essential contributor to plaque growth, composition and initiation. It is sensed by endothelial cells, which react to blood flow by expressing > 1000 genes. The sheer number of genes implies that one needs genomic techniques to unravel their response in disease. Individual genomic studies have been performed but lack sufficient power to identify subtle changes in gene expression. In this study, we investigated whether a systematic meta-analysis of available microarray studies can improve their consistency. We identified 17 studies using microarrays, of which six were performed in vivo and 11 in vitro. The in vivo studies were disregarded due to the lack of the shear profile. Of the in vitro studies, a cross-platform integration of human studies (HUVECs in flow cells) showed high concordance (> 90 %). The human data set identified > 1600 genes to be shear responsive, more than any other study and in this gene set all known mechanosensitive genes and pathways were present. A detailed network analysis indicated a power distribution (e. g. the presence of hubs), without a hierarchical organisation. The average cluster coefficient was high and further analysis indicated an aggregation of 3 and 4 element motifs, indicating a high prevalence of feedback and feed forward loops, similar to prokaryotic cells. In conclusion, this initial study presented a novel method to integrate human-based mechanosensitive studies to increase its power. The robust network was large, contained all known mechanosensitive pathways and its structure revealed hubs, and a large aggregate of feedback and feed forward loops.
    No preview · Article · Feb 2016 · Thrombosis and Haemostasis
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    ABSTRACT: Flow chambers are common tools used for studying thrombus formation in vitro. However, the use of such devices is not standardised and there is a large diversity among the flow chamber systems currently used, and also in the methods used for quantifying the thrombus development. It was the study objective to evaluate a new method for analysis and quantification of platelet thrombus formation that can facilitates comparison of results between research groups. Whole blood was drawn over a collagen patch in commercial Ibid or in-house constructed PDMS flow chambers. Five percent of the platelets were fluorescently labelled and z-stack time-lapse images were captured during thrombus formation. Images were processed in a Python script in which the number of platelets and their respective x-, y- and z-positions were obtained. For comparison with existing methods the platelets were also labelled and quantified using fluorescence intensity and thrombus volume estimations by confocal microscopy. The presented method was found less sensitive to microscope and image adjustments and provides more details on thrombus development dynamics than the methods for measuring fluorescence intensity and thrombus volume estimation. The platelet count method produced comparable results with commercial and PDMS flow chambers, and could also obtain information regarding the stability of each detected platelet in the thrombus. In conclusion, quantification of thrombus formation by platelet count is a sensitive and robust method that enables measurement of platelet accumulation and platelet stability in an absolute scale that could be used for comparisons between research groups.
    No preview · Article · Feb 2016 · Thrombosis and Haemostasis
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    ABSTRACT: PreImplantation factor (PIF) is a 15-amino acid peptide endogenously secreted by viable embryos, regulating/enabling maternal (host) acceptance/tolerance to the "invading" embryo (allograft) all-while preserving maternal immunity to fight infections. Such attributes make PIF a potential therapeutic agent for chronic inflammatory diseases. We investigated whether PIF's immunomodulatory properties prevent progression of atherosclerosis in the hyper-cholesterolaemic ApoE-deficient murine model. Male, high-fat diet fed, ApoE-deficient (ApoE-/-) mice were administered either PBS, scrambled PIF (0.3-3 mg/kg) or PIF (0.3-3 mg/kg) for seven weeks. After treatment, PIF (3 mg/kg)-treated ApoE-/- mice displayed significantly reduced atherosclerosis lesion burden in the aortic sinus and aortic arch, without any effect on lipid profile. PIF also caused a significant reduction in infiltration of macrophages, decreased expression of pro-inflammatory adhesion molecules, cytokines and chemokines in the plaque, and reduced circulating IFN-γ levels. PIF preferentially binds to monocytes/neutrophils. In vitro, PIF attenuated monocyte migration (MCP-1-induced chemotaxis assay) and in vivo in LPS peritonitis model. Also PIF prevented leukocyte extravasation (peritonitis thioglycollate-induced model), demonstrating that PIF exerts its effect in part by modulation of monocyte function. Inhibition of the potassium channel KCNAB3 (Kv1.3) and of the insulin degrading enzyme (IDE) was demonstrated as potential mechanism of PIF's immunomodulatory effects. In conclusion, PIF regulates/lowers inflammation and prevents atherosclerosis development without affecting circulating lipids. Overall our findings establish PIF as a strong immunomodulatory drug candidate for atherosclerosis therapy.
    No preview · Article · Feb 2016 · Thrombosis and Haemostasis

  • No preview · Article · Feb 2016 · Thrombosis and Haemostasis
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    ABSTRACT: Vitamin K antagonists are currently recommended in patients with 'valvular' atrial fibrillation (AF), e. g. those having mitral stenosis or artificial heart valves. We compared thromboembolic risk in patients with 'non valvular' AF and in those with AF and biological valve replacement (valve bioprosthesis). Among 8962 AF patients seen between 2000 and 2010, a diagnosis of 'non-valvular AF' was found in 8053 (94 %). Among patients with 'valvular' AF, 549 (6 %) had a biological prosthesis. The patients with bioprosthesis were older and had a higher CHA2DS2-VASc score than those with non valvular AF. After a follow-up of 876 ± 1048 days (median 400 days, interquartile range 12-1483), the occurrence of thromboembolic events was similar in AF patients with bioprosthesis compared to those with 'non valvular' AF (hazard ratio [HR] 1.10 95 % confidence interval [CI] 0.83-1.45, p=0.52, adjusted HR 0.93, 95 %CI 0.68-1.25, p=0.61). Factors independently associated with increased risk of stroke/TE events were older age (HR 1.25, 95 %CI 1.16-1.34 per 10-year increase, p< 0.0001) and higher CHA2DS2-VASc score (HR 1.35, 95 %CI 1.24-1.46, p< 0.0001) whilst female gender (HR 0.75, 95 %CI 0.62-0.90, p=0.002), use of vitamin K antagonist (HR 0.83, 95 %CI 0.71-0.98, p=0.03) were independently associated with a lower risk of stroke/TE. Neither the presence of bioprosthesis nor the location of bioprosthesis was independent predictor for TE events. In conclusion, AF patients with bioprosthesis had a non-significantly higher risk of stroke/TE events compared to patients with non-valvular AF. Second, the CHA2DS2-VASc score was independently associated with an increased risk of TE events, and was a valuable determinant of TE risk both in AF patients with non-valvular AF as well as those with bioprosthesis, whether treated or not treated with OAC.
    No preview · Article · Feb 2016 · Thrombosis and Haemostasis
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    ABSTRACT: Coagulation markers may improve monitoring the risk of stroke and bleeding in patients with atrial fibrillation (AF) during anticoagulant treatment. We examined baseline levels of D-dimer and their association with stroke, cardiovascular death and major bleeding in 6,202 AF patients randomised to dabigatran or warfarin in the RE-LY trial. The effects of treatment on serial levels of D-dimer and coagulation factor (F) VIIa in 2,567 patients were also analysed. Baseline D-dimer levels were related to the rate of stroke/systemic embolism (SEE) with 0.64 % in the lowest quartile (Q1, as reference) (D-dimer < 298 µg/l), 1.38 % Q2 (D-dimer 298-473 µg/l), 1.71 % Q3 (D-dimer 474-822 µg/l) and 2.00 % in Q4 (D-dimer > 822 µg/l) (p=0.0007). Similar associations were shown for cardiovascular death and major bleeding. Addition of baseline D-dimer to established clinical risk factors improved prediction of stroke/SEE, cardiovascular death and major bleeding (C-index increased from 0.66 to 0.68, 0.71 to 0.73 and 0.66 to 0.67, respectively). Dabigatran provided a greater reduction of D-dimer levels than warfarin regardless of baseline anticoagulant treatment. On-treatment levels of FVIIa were markedly reduced by warfarin (median 12.1-13.8 mU/ml) but significantly higher with dabigatran (median 39.4-49.0 mU/ml) at all-time points. Dabigatran is associated with greater reduction in D-dimer without the pronounced reduction of FVIIa seen with warfarin. These different effects on the coagulation system might explain the better efficacy and less intracranial bleeding observed with dabigatran compared with warfarin.
    No preview · Article · Jan 2016 · Thrombosis and Haemostasis
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    ABSTRACT: Antiphospholipid syndrome (APS) is an autoimmune disease characterised by the presence of antiphospholipid antibodies (aPL) associated with increased thrombotic risk and pregnancy morbidity. Although aPL are heterogeneous auto-antibodies, the major pathogenic target is the plasma protein β2-glycoprotein 1. The molecular mechanisms of platelet activation by aPL remain poorly understood. Here, we explored the role of the class IA phosphoinositide 3-kinase (PI3K) α and β isoforms in platelet activation by aPL. Compared to control IgG from healthy individuals, the IgG fraction isolated from patients with APS potentiates platelet aggregation induced by low dose of thrombin in vitro and increases platelet adhesion and thrombus growth on a collagen matrix under arterial shear rate through a mechanism involving glycoprotein Ib (GPIb) and Toll Like Receptor 2 (TLR-2). Using isoforms-selective pharmacological PI3K inhibitors and mice with megakaryocyte/platelet lineage-specific inactivation of class IA PI3K isoforms, we demonstrate a critical role of the PI3Kβ and PI3Kα isoforms in platelet activation induced by aPL. Our data show that aPL potentiate platelet activation through GPIbα and TLR-2 via a mechanism involving the class IA PI3Kα and β isoforms, which represent new potential therapeutic targets in the prevention or treatment of thrombotic events in patients with APS.
    No preview · Article · Jan 2016 · Thrombosis and Haemostasis
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    ABSTRACT: The SAMe-TT2R2 score has recently been proposed to predict the quality of vitamin K antagonist (VKA) anticoagulation control in patients with atrial fibrillation. We aimed at investigating whether the score is effective also in patients with venous thromboembolism (VTE). Patients included in the START-Register because started VKA therapy for a recent VTE episode and with > 3 months follow-up were analyzed. The score was calculated using the baseline patient's characteristics present in the electronic database of the registry, where all INR results were also available and analysed to calculate the time in therapeutic range (TTR). A total of 1308 patients (53.4 % female, median age 68 years) were analysed. During 998 patient-years follow-up, the median TTR was 63 %. The maximum score in the patients was 4, with 70 % of them having 0-1. INR controls within range (2.0-3.0) were significantly less prevalent in patients with score ≥ 2 vs 0-1 score (58.5 ± 20 % vs 61.5 ± 19 %, respectively, p = 0.046). Patients with score ≥ 2 vs 0-1 had a highly significant lower TTR during the first 3 months of therapy (53 ± 26 % and 61 ± 26 %, respectively; p=0.0001), difference mainly due to more time spent below 2.0 INR (38 ± 28 % vs 31.3 ± 26.7 %, respectively; p=0.0001). In conclusion, the study proved, for the first time, that the SAMe-TT2R2 score is useful to predict among VTE patients those who will have good (score 0-1) or less good (score ≥ 2) VKA anticoagulation control. The score can help decision-making in everyday clinical practice, especially when choosing between VKA and non-vitamin K antagonists direct anticoagulants.
    No preview · Article · Jan 2016 · Thrombosis and Haemostasis
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    ABSTRACT: We aimed to determine whether statin use is associated with a decreased risk of recurrent venous thromboembolism (VTE) in older patients. We used a pre-assembled cohort of patients at least 65 years of age diagnosed with incident VTE between January 1, 1994 and December 31, 2004 in the province of Québec, Canada and followed until December 31, 2005. Time-dependent Cox proportional hazards models were used to estimate adjusted hazard ratios (HRs) and 95 % confidence intervals (CIs) of recurrent VTE associated with current and past use of statins, compared with non-use. The cohort included 25,681 patients with incident VTE. During a mean follow-up of 3.0 years, there were 2343 recurrent VTE events (rate: 3.1 per 100 person-years). Compared with non-use, current use of statins was associated with a decreased risk of VTE recurrence (rates: 1.55 vs 3.47 per 100 per year, respectively; HR: 0.74, 95 % CI: 0.61-0.89), while no association was observed with past use (HR: 0.98, 95 % CI: 0.76-1.25). In a secondary analysis, longer durations of statin use were associated with greater risk reductions (0-6 months, HR 0.82, 95 % CI: 0.67-1.01; 6-12 months, HR 0.62, 95 % CI: 0.43-0.90; ≥ 12 months, HR: 0.50, 95 % CI: 0.33-0.74; p-value for trend ≤ 0.001). The use of statin was associated with a decreased risk of recurrent VTE in older patients. This study supports the need for randomised controlled trials to assess the efficacy and safety of statins in the long-term treatment of VTE.
    No preview · Article · Jan 2016 · Thrombosis and Haemostasis
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    ABSTRACT: Current therapy for haemophilia A is guided by severity of the disease, which in turn is best reflected in patients' endogenous factor VIII activity levels. For patients with severe haemophilia (particularly children), prophylaxis with continuous routine factor replacement has become standard of care in developed countries and is gradually becoming the standard of care in developing countries. The question arises then: what is an appropriate prophylaxis regimen to prevent bleeding events and arthropathy, while also maximizing patient quality of life and taking into consideration the costs of prophylaxis? Should all patients be treated with one standard, fixed prophylaxis regimen, or should prophylaxis be individualised for each patient? If so, what factors need to be considered in choosing the appropriate dose and frequency of factor administration? If prophylaxis is tailored to the individual patient, then patient-related factors (bleeding phenotype, activity profiles, age, joint status) and product-specific factors (half-life of the replacement factor in the individual patient) will determine the choice of regimen, whether it be a fixed-regimen prophylaxis or prophylaxis that is tailored to patient activity and bleeding risk. Regardless of the choice of prophylaxis regimen, for any regimen to be effective, adherence to therapy is key to optimising outcomes.
    Preview · Article · Jan 2016 · Thrombosis and Haemostasis
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    ABSTRACT: Treatment with granulocyte-colony stimulating factor (G-CSF) mobilises cells from the bone marrow to the peripheral blood. Previous preclinical and early clinical trials may suggest that treatment with G-CSF leads to improved myocardial perfusion and function in acute or chronic ischaemic heart disease. In the REVIVAL-2 study we found that stem cell mobilisation by G-CSF does not influence infarct size, left ventricular function and coronary restenosis in patients with acute myocardial infarction (MI) that underwent successful percutaneous coronary intervention. The objective of the present analysis was to assess the impact of G-CSF treatment on seven-year clinical outcomes from the REVIVAL-2 trial. In the randomized, double-blind, placebo-controlled REVIVAL-2 study, 114 patients with the diagnosis of acute myocardial infarction were enrolled five days after successful reperfusion by percutaneous coronary intervention. Patients were assigned to receive 10 µg/kg G-CSF (n=56) or placebo (n=58) for five days. The primary endpoint for this long-term outcome analysis was the composite of death, myocardial infarction or stroke seven years after randomisation. The endpoint occurred in 14.3 % of patients in the G-CSF group versus 17.2 % assigned to placebo (p=0.67). The combined incidence of death or myocardial infarction occurred in 14.3 % of the patients assigned to G-CSF and 15.5 % of the patients assigned to placebo (p=0.85). In conclusion, these long-term follow-up data show that G-CSF does not improve clinical outcomes of patients with acute myocardial infarction.
    No preview · Article · Jan 2016 · Thrombosis and Haemostasis
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    ABSTRACT: Prophylaxis is the recommended treatment for children with severe haemophilia A, but whether prophylaxis should be continued in adulthood is still under debate. Previous studies with limited follow-up have suggested that some patients may be able to stop prophylaxis in adulthood, while maintaining good joint health. This single-centre observational cohort study examined patients with severe haemophilia A born 1970-1988 without inhibitor development, and assessed the long-term consequences of discontinuing prophylaxis Patient-initiated changes in prophylaxis, including all switches to on-demand treatment lasting a minimum of two consecutive weeks, were recorded from the time self-infusion began until the last evaluation. Sixty-six patients were evaluated at a median age of 32.4 years: 26 % of patients had stopped prophylaxis for a median of 10 years, 15 % had interrupted prophylaxis and 59 % had continued prophylaxis. Annual joint bleeding rate (AJBR), Haemophilia Joint Health Score (HJHS-2.1; 0-124 points), Radiological Pettersson score (0-78 points) and Haemophilia Activities List score (HAL; 100-0 points) were compared between patients who stopped and patients who continued prophylaxis. Although self-reported bleeding rates and functional limitations were similar in both groups (AJBR: 1.5 vs 1.2 and HAL: 84 vs 84 for those who stopped and continued prophylaxis, respectively), objective assessment of joint status showed increased arthropathy, after 10 years of on-demand treatment in patients who stopped prophylaxis compared with those who continued (HJHS: 23 vs. 14 and Pettersson: 16 vs 5, respectively; P< 0.01). These results support continuation of long-term prophylaxis in adults and demonstrate the need for objective monitoring of joint status.
    No preview · Article · Jan 2016 · Thrombosis and Haemostasis
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    ABSTRACT: An increasing body of data suggests that East Asian patients have differing risk profiles for both thrombophilia and bleeding compared with Western population. This study was designed to evaluate the relationship of bleeding to platelet function in East Asians undergoing percutaneous coronary intervention (PCI). Patients who had undergone uneventful PCI (n= 301) were prospectively enrolled and bleeding events were evaluated during dual antiplatelet therapy (DAPT) with aspirin and clopidogrel. Platelet function was measured during hospitalisation and at 30-day follow-up by light transmittance aggregometry (LTA) and vasodilator-stimulated phosphoprotein phosphorylation (VASP-P) assay. During 30-day follow-up, 29.2 % of patients (n= 88) experienced post-discharge Bleeding Academic Research Consortium (BARC) complications (24.6 % and 7.0 % of BARC type 1 and 2, respectively). Patients presenting with acute myocardial infarction had fewer episodes of type 1 BARC bleeding (odds ratio: 0.41; 95 % confidence interval: 0.22 to 0.76; p= 0.005). The cut-off of low platelet reactivity (LPR) (20 µM ADP-induced platelet aggregation ≤ 46.1 %; platelet reactivity index ≤ 45.1 %) was the independent determinant of type 2 BARC bleeding (odds ratio: 3.55 and 4.44; p= 0.009 and 0.002, respectively). The first 30-day BARC bleeding episodes were associated with an increased rate of subsequent premature DAPT discontinuation during one-year follow-up (4.7 % vs 11.4 %; odds ratio: 2.60; 95 % confidence interval: 1.04 to 6.50; p= 0.035). In conclusion, among East Asians, mild bleeding episodes are common early after PCI and are associated with premature DAPT discontinuation. Type 2 BARC bleeding episodes are associated with LPR cut-offs measured at 30 days post-discharge.
    No preview · Article · Jan 2016 · Thrombosis and Haemostasis
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    ABSTRACT: Von Willebrand disease-type 2A (VWD-2A) and acquired von Willebrand syndrome (AVWS) due to aortic stenosis (AS) or left ventricular assist device (LVAD) are associated with an increased proteolysis of von Willebrand factor (VWF). Analysis of VWF multimeric profile is the most sensitive way to assess such increased VWF-proteolysis. However, several technical aspects hamper a large diffusion among routine diagnosis laboratories. This makes early diagnosis and early appropriate care of increased proteolysis challenging. In this context of unmet medical need, we developed a new ELISA aiming a quick, easy and reliable assessment of VWF-proteolysis. This ELISA was assessed successively in a LVAD-model, healthy subjects (n=39), acquired TTP-patients (n=4), VWD-patients (including VWD-2A(IIA), n=22; VWD-2B, n=26; VWD-2A(IIE), n=21; and VWD-1C, n=8) and in AVWS-patients (AS, n=9; LVAD, n=9; and MGUS, n=8). A standard of VWF-proteolysis was specifically developed. Extent of VWF-proteolysis was expressed as relative percentage and as VWF proteolysis/VWF:Ag ratio. A speed-dependent increase in VWF-proteolysis was assessed in the LVAD model whereas no proteolysis was observed in TTP-patients. In VWD-patients, VWF-proteolysis was significantly increased in VWD-2A(IIA) and VWD-2B and significantly decreased in VWD-2A(IIE) versus controls (p< 0.0001). In AVWS-patients, VWF-proteolysis was significantly increased in AS- and LVAD-patients compared to controls (p< 0.0001) and not detectable in MGUS-patients. A significant increase in VWF-proteolysis was detected as soon as three hours after LVAD implantation (p< 0.01). In conclusion, we describe a new ELISA allowing a rapid and accurate diagnosis of VWF-proteolysis validated in three different clinical situations. This assay represents a helpful alternative to electrophoresis-based assay in the diagnosis and management of AVWS with increased VWF-proteolysis.
    No preview · Article · Jan 2016 · Thrombosis and Haemostasis