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  1. Article: Practical Nomogram Predicting Apixaban or Rivaroxaban Concentrations from Low-Molecular-Weight Heparin Anti-Xa Values: Special Interest in Acute Ischemic Stroke Patients.

    Brakta, Charlyne / Stépanian, Alain / Reiner, Peggy / Delrue, Maxime / Mazighi, Mikaël / Curis, Emmanuel / Siguret, Virginie

    Journal of stroke

    2023  Volume 25, Issue 1, Page(s) 126–131

    Abstract: Background and purpose: In patients with acute ischemic stroke (AIS) using a direct oral factor-Xa anticoagulant (DOAC) during the last 48 hours, a fixed plasma heparin-calibrated anti-Xa activity (0.5 IU/mL) was proposed as a threshold below which ... ...

    Abstract Background and purpose: In patients with acute ischemic stroke (AIS) using a direct oral factor-Xa anticoagulant (DOAC) during the last 48 hours, a fixed plasma heparin-calibrated anti-Xa activity (0.5 IU/mL) was proposed as a threshold below which patients could be eligible for thrombolysis and/or thrombectomy. Besides, specific DOAC-calibrated anti-Xa thresholds up to 50 ng/mL have been proposed. However, specific DOAC assays are not widely available contrarily to low-molecularweight heparin (LMWH) anti-Xa activity. We developed and validated a nomogram for predicting apixaban and rivaroxaban concentrations based on LMWH anti-Xa assay.
    Methods: Our prospective study included apixaban (n=325) and rivaroxaban (n=276) patients. On the same sample, we systematically measured specific DOAC concentration and LMWH anti-Xa activity, using STA®-Liquid-Anti-Xa (Stago) and specific DOAC- or LMWH-calibrators, respectively. The nomogram was built using quantifiable values for both assays on the derivation cohorts with a log-linear regression model. Model performances including sensitivity, specificity, and true positive rate for different thresholds were checked on the validation cohorts.
    Results: The models built from the derivation cohorts predicted that values <30 ng/mL and <50 ng/ mL DOAC thresholds corresponded to LMWH-anti-Xa values <0.10 IU/mL and <0.64 IU/mL for apixaban; <0.10 IU/mL and <0.71 IU/mL for rivaroxaban. The model accurately predicted apixaban/ rivaroxaban concentrations in the validation cohort.
    Conclusions: This easy-to-use nomogram, developed with our reagent, allowed accurately predicting DOAC concentrations based on LMWH-anti-Xa results in emergency situations such as AIS when drug-specific assessments are not rapidly available. Using DOAC <50 ng/mL equivalent threshold, instead of the fixed LMWH <0.5 IU/mL one, would allow proposing thrombolysis to more patients.
    Language English
    Publishing date 2023-01-03
    Publishing country Korea (South)
    Document type Journal Article
    ZDB-ID 2814366-8
    ISSN 2287-6405 ; 2287-6391
    ISSN (online) 2287-6405
    ISSN 2287-6391
    DOI 10.5853/jos.2022.03034
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Understanding pathophysiology of hemostasis disorders in critically ill patients with COVID-19.

    Joly, Bérangère S / Siguret, Virginie / Veyradier, Agnès

    Intensive care medicine

    2020  Volume 46, Issue 8, Page(s) 1603–1606

    MeSH term(s) Anticoagulants/therapeutic use ; Betacoronavirus/physiology ; Blood Coagulation Disorders/drug therapy ; Blood Coagulation Disorders/etiology ; COVID-19 ; Coronavirus Infections/complications ; Coronavirus Infections/immunology ; Coronavirus Infections/physiopathology ; Critical Illness ; Cytokine Release Syndrome/etiology ; Hemostasis/physiology ; Humans ; Pandemics ; Pneumonia, Viral/complications ; Pneumonia, Viral/immunology ; Pneumonia, Viral/physiopathology ; SARS-CoV-2
    Chemical Substances Anticoagulants
    Keywords covid19
    Language English
    Publishing date 2020-05-15
    Publishing country United States
    Document type Journal Article
    ZDB-ID 80387-x
    ISSN 1432-1238 ; 0340-0964 ; 0342-4642 ; 0935-1701
    ISSN (online) 1432-1238
    ISSN 0340-0964 ; 0342-4642 ; 0935-1701
    DOI 10.1007/s00134-020-06088-1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Unexpected acute pulmonary embolism in an old COVID-19 patient with warfarin overdose: a case report.

    Coutrot, Maxime / Delrue, Maxime / Joly, Bérangère S / Siguret, Virginie

    European heart journal. Case reports

    2021  Volume 5, Issue 6, Page(s) ytab206

    Abstract: Background: Severe acute respiratory syndrome coronavirus 2 disease is strongly associated with a high incidence of thrombotic events. Anticoagulation could be a cornerstone in successfully managing severe forms of coronavirus disease 2019 (COVID-19). ... ...

    Abstract Background: Severe acute respiratory syndrome coronavirus 2 disease is strongly associated with a high incidence of thrombotic events. Anticoagulation could be a cornerstone in successfully managing severe forms of coronavirus disease 2019 (COVID-19). However, optimal anticoagulant dosing in elderly patients is challenging because of high risk of both thrombosis and bleeding.
    Case summary: We present here the case of an 89-year-old patient receiving warfarin for atrial fibrillation and valvular heart disease, admitted to the intensive care unit for respiratory failure due to COVID-19. The patient presented with a severe epistaxis associated with warfarin overdose [international normalized ratio (INR) > 10]. After a successful initial reversal using vitamin K
    Discussion: This case report illustrates the complexity of COVID-19 pathophysiology and its management for physicians, especially in patients receiving vitamin K antagonists (VKAs). Infection, concurrent medication use, and pharmacogenetic factors involved in VKA metabolism and pharmacodynamics may lead to a loss of control of anticoagulation. Pulmonary embolism should still be considered in COVID-19 patients even with effective or overdosed anticoagulant therapy.
    Language English
    Publishing date 2021-06-05
    Publishing country England
    Document type Case Reports
    ISSN 2514-2119
    ISSN (online) 2514-2119
    DOI 10.1093/ehjcr/ytab206
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Is there a role for the laboratory monitoring in the management of specific antidotes of direct oral anticoagulants?

    Gendron, Nicolas / Billoir, Paul / Siguret, Virginie / Le Cam-Duchez, Véronique / Proulle, Valérie / Macchi, Laurent / Boissier, Elodie / Mouton, Christine / De Maistre, Emmanuel / Gouin-Thibault, Isabelle / Jourdi, Georges

    Thrombosis research

    2024  Volume 237, Page(s) 171–180

    Abstract: Given the growing number of patients receiving direct oral anticoagulant (DOAC), patients requiring rapid neutralization is also increasing in case of major bleedings or urgent surgery/procedures. Idarucizumab is commercialized as a specific antidote to ... ...

    Abstract Given the growing number of patients receiving direct oral anticoagulant (DOAC), patients requiring rapid neutralization is also increasing in case of major bleedings or urgent surgery/procedures. Idarucizumab is commercialized as a specific antidote to dabigatran while andexanet alfa has gained the Food and Drug Administration and the European Medicines Agency approval as an oral anti-factor Xa inhibitors antidote. Other antidotes or hemostatic agents are still under preclinical or clinical development, the most advanced being ciraparantag. DOAC plasma levels measurement allows to appropriately select patient for antidote administration and may prevent unnecessary prescription of expensive molecules in some acute clinical settings. However, these tests might be inconclusive after some antidote administration, namely andexanet alfa and ciraparantag. The benefit of laboratory monitoring following DOAC reversal remains unclear. Here, we sought to provide an overview of the key studies evaluating the safety and efficacy of DOAC reversal using the most developed/commercialized specific antidotes, to discuss the potential role of the laboratory monitoring in the management of patients receiving DOAC specific antidotes and to highlight the areas that deserve further investigations in order to establish the exact role of laboratory monitoring in the appropriate management of DOAC specific antidotes.
    Language English
    Publishing date 2024-04-10
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 121852-9
    ISSN 1879-2472 ; 0049-3848
    ISSN (online) 1879-2472
    ISSN 0049-3848
    DOI 10.1016/j.thromres.2024.04.005
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Bothrops venom-induced hemostasis disorders in the rat: Between Scylla and Charybdis.

    Larréché, Sébastien / Chevillard, Lucie / Jourdi, Georges / Mathé, Simon / Servonnet, Aurélie / Joly, Bérangère S / Siguret, Virginie / Chippaux, Jean-Philippe / Mégarbane, Bruno

    PLoS neglected tropical diseases

    2023  Volume 17, Issue 11, Page(s) e0011786

    Abstract: Hemostasis impairment represents the most threatening consequence of Viperidae envenoming, notably with Bothrops genus. In the French departments of America, B. atrox envenomation in French Guiana may lead to bleeding while B. lanceolatus envenomation in ...

    Abstract Hemostasis impairment represents the most threatening consequence of Viperidae envenoming, notably with Bothrops genus. In the French departments of America, B. atrox envenomation in French Guiana may lead to bleeding while B. lanceolatus envenomation in Martinique to thrombosis. Bleeding related to B. atrox envenomation is attributed to vascular damage mediated by venom metalloproteinases and blood uncoagulable state resulting from thrombocytopenia and consumptive coagulopathy. Thrombosis related to B. lanceolatus envenomation are poorly understood. We aimed to compare the effects of B. atrox and B. lanceolatus venoms in the rat to identify the determinants of the hemorrhagic versus thrombotic complications. Viscoelastometry (ROTEM), platelet count, plasma fibrinogen, thrombin generation assay, fibrinography, endothelial (von Willebrand factor, ADAMTS13 activity, ICAM-1, and soluble E-selectin), and inflammatory biomarkers (IL-1β, IL-6, TNF-α, MCP-1, and PAI-1) were determined in blood samples obtained at H3, H6, and H24 after the subcutaneous venom versus saline injection. In comparison to the control, initial fibrinogen consumption was observed with the two venoms while thrombocytopenia and reduction in the clot amplitude only with B. atrox venom. Moreover, we showed an increase in thrombin generation at H3 with the two venoms, an increase in fibrin generation accompanied with hyperfibrinogenemia at H24 and an increase in inflammatory biomarkers with B. lanceolatus venom. No endothelial damage was found with the two venoms. To conclude, our data support two-sided hemostasis complications in Bothrops envenoming with an initial risk of hemorrhage related to platelet consumption and hypocoagulability followed by an increased risk of thrombosis promoted by the activated inflammatory response and rapid-onset fibrinogen restoration.
    MeSH term(s) Rats ; Animals ; Thrombin/adverse effects ; Crotalid Venoms/toxicity ; Hemostasis ; Hemorrhage ; Blood Coagulation Disorders ; Fibrinogen ; Thrombocytopenia ; Thrombosis/chemically induced ; Biomarkers ; Bothrops/physiology ; Snake Bites/complications
    Chemical Substances Thrombin (EC 3.4.21.5) ; Crotalid Venoms ; Fibrinogen (9001-32-5) ; Biomarkers
    Language English
    Publishing date 2023-11-27
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2429704-5
    ISSN 1935-2735 ; 1935-2735
    ISSN (online) 1935-2735
    ISSN 1935-2735
    DOI 10.1371/journal.pntd.0011786
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Importance of cytochrome 3A4 and 2D6-mediated drug-drug interactions in oxycodone consumption among older adults hospitalized for hip fracture: a cross-sectional study.

    Decaix, Théodore / Gautier, Sylvain / Royer, Luca / Laprévote, Olivier / Tritz, Thomas / Siguret, Virginie / Teillet, Laurent / Sellier, Cyril / Pépin, Marion

    Aging clinical and experimental research

    2023  Volume 35, Issue 11, Page(s) 2471–2481

    Abstract: Hip fracture is a common injury and represents a major health problem with an increasing incidence. In older adults, opioids such as oxycodone are often preferred to other analgesics such as tramadol because of a lower risk of delirium. Different ... ...

    Abstract Hip fracture is a common injury and represents a major health problem with an increasing incidence. In older adults, opioids such as oxycodone are often preferred to other analgesics such as tramadol because of a lower risk of delirium. Different parameters, such as inhibition of cytochrome P450 (CYP450) 2D6 and/or 3A4, can potentially lead to pharmacokinetic variations of oxycodone representing a risk of adverse drugs effects or lack of drug response. There is a risk of drug-drug interactions involving CYP450 in older adults due to the high prevalence of polypharmacy. This study sought to identify patient characteristics that influence oxycodone administration. A single-center observational study included 355 patients with a hip fracture hospitalized in a geriatric postoperative unit. Composite endpoint based on form, duration, and timing to intake separated patients into three groups: "no oxycodone", "low oxycodone ", and "high oxycodone ". CYP450 interactions were studied based on a composite variable defining the most involved CYP450 pathways between CYP2D6 and CYP3A4. CYP450 interactions with CYP2D6 pathway involved were associated with the risk of "high oxycodone" [odds ratio adjusted on age and the type of hip fracture (OR*) 4.52, 95% confidence interval (CI) 1.39-16.83, p = 0.02)], as well as serum albumin levels (OR* 1.09, 95% CI 1.02-1.17, p = 0.01). Cognitive impairment was negatively associated with the risk of "high oxycodone" (OR* 0.38, 95% CI 0.18-0.77, p = 0.02). This study showed an association between CYP2D6 interactions and higher oxycodone consumption indirectly reflecting the existence of uncontrolled postoperative pain.
    MeSH term(s) Humans ; Aged ; Oxycodone/adverse effects ; Cross-Sectional Studies ; Cytochrome P-450 CYP2D6/metabolism ; Cytochrome P-450 CYP2D6 Inhibitors ; Analgesics, Opioid/adverse effects ; Drug Interactions ; Hip Fractures
    Chemical Substances Oxycodone (CD35PMG570) ; Cytochrome P-450 CYP2D6 (EC 1.14.14.1) ; Cytochrome P-450 CYP2D6 Inhibitors ; Analgesics, Opioid
    Language English
    Publishing date 2023-10-20
    Publishing country Germany
    Document type Observational Study ; Journal Article
    ZDB-ID 2104785-6
    ISSN 1720-8319 ; 1594-0667
    ISSN (online) 1720-8319
    ISSN 1594-0667
    DOI 10.1007/s40520-023-02569-7
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Bothrops atrox

    Larréché, Sébastien / Bousquet, Aurore / Chevillard, Lucie / Gahoual, Rabah / Jourdi, Georges / Dupart, Anne-Laure / Bachelot-Loza, Christilla / Gaussem, Pascale / Siguret, Virginie / Chippaux, Jean-Philippe / Mégarbane, Bruno

    Toxins

    2023  Volume 15, Issue 10

    Abstract: ... ...

    Abstract Bothrops
    MeSH term(s) Animals ; Antivenins/pharmacology ; Bothrops ; Calcium ; Hemorrhage/chemically induced ; Hemorrhage/drug therapy ; Crotalid Venoms/toxicity ; Thrombosis ; Snake Bites
    Chemical Substances Antivenins ; Calcium (SY7Q814VUP) ; Crotalid Venoms
    Language English
    Publishing date 2023-10-16
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2518395-3
    ISSN 2072-6651 ; 2072-6651
    ISSN (online) 2072-6651
    ISSN 2072-6651
    DOI 10.3390/toxins15100614
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Understanding pathophysiology of hemostasis disorders in critically ill patients with COVID-19

    Joly, Bérangère S. / Siguret, Virginie / Veyradier, Agnès

    Intensive Care Medicine

    2020  Volume 46, Issue 8, Page(s) 1603–1606

    Keywords Critical Care and Intensive Care Medicine ; covid19
    Language English
    Publisher Springer Science and Business Media LLC
    Publishing country us
    Document type Article ; Online
    ZDB-ID 80387-x
    ISSN 1432-1238 ; 0340-0964 ; 0342-4642 ; 0935-1701
    ISSN (online) 1432-1238
    ISSN 0340-0964 ; 0342-4642 ; 0935-1701
    DOI 10.1007/s00134-020-06088-1
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article ; Online: Tinzaparin Sodium Pharmacokinetics in Patients with Chronic Kidney Disease: Practical Implications.

    Helfer, Hélène / Siguret, Virginie / Mahé, Isabelle

    American journal of cardiovascular drugs : drugs, devices, and other interventions

    2019  Volume 20, Issue 3, Page(s) 223–228

    Abstract: Low-molecular-weight heparins (LMWHs) are the mainstay of the prophylaxis and treatment of venous thromboembolism (VTE). Due to their renal elimination, the risk of accumulation with the related bleeding risk may represent a limitation for the use of ... ...

    Abstract Low-molecular-weight heparins (LMWHs) are the mainstay of the prophylaxis and treatment of venous thromboembolism (VTE). Due to their renal elimination, the risk of accumulation with the related bleeding risk may represent a limitation for the use of LMWHs in patients with chronic kidney disease (CKD) as the risk of major bleeding is increased in patients with creatinine clearance (CrCl) < 30 mL/min, especially in patients with cancer. LMWH structure and molecular weight (MW) are heterogeneous among available agents. The elimination of tinzaparin, which has the highest mean MW among LMWHs, is less dependent on renal function as it is also metabolized through the reticuloendothelial system. A subcutaneous therapeutic dose of tinzaparin (175 IU/kg) once daily has been shown to cause no accumulation of anti-factor Xa activity in patients with CrCl ≥ 20 mL/min. Clinical experience from randomized controlled studies has shown no significant impact of CKD on bleeding risk in cancer patients receiving treatment doses of tinzaparin. This suggests that in these patients the use of treatment doses of tinzaparin does not require anticoagulation monitoring or dose adjustment.
    MeSH term(s) Fibrinolytic Agents/pharmacokinetics ; Hemorrhage/chemically induced ; Hemorrhage/prevention & control ; Humans ; Renal Elimination ; Renal Insufficiency, Chronic/complications ; Renal Insufficiency, Chronic/metabolism ; Risk Adjustment ; Tinzaparin/pharmacokinetics ; Venous Thromboembolism/complications ; Venous Thromboembolism/drug therapy
    Chemical Substances Fibrinolytic Agents ; Tinzaparin (7UQ7X4Y489)
    Language English
    Publishing date 2019-11-11
    Publishing country New Zealand
    Document type Journal Article ; Review
    ZDB-ID 2052547-3
    ISSN 1179-187X ; 1175-3277
    ISSN (online) 1179-187X
    ISSN 1175-3277
    DOI 10.1007/s40256-019-00382-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

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