Management of major bleeding complications and emergency surgery in patients on long-term treatment with direct oral anticoagulants, thrombin or factor-Xa inhibitors. Proposals of the Working Group on Perioperative Haemostasis (GIHP) - March 2013 [Prise en charge des complications hémorragiques graves et de la chirurgie en urgence chez les patients recevant un anticoagulant oral anti-IIa ou anti-Xa direct. Propositions du Groupe dintérêt en Hémostase Périopératoire (GIHP) - mars 2013]
Pernod G.,Grenoble University Hospital Center |
Pernod G.,CNRS Complex Medical Engineering Laboratory |
Albaladejo P.,CNRS Complex Medical Engineering Laboratory |
Albaladejo P.,Grenoble University Hospital Center |
And 13 more authors.
Annales Francaises d'Anesthesie et de Reanimation | Year: 2013
New direct oral anticoagulants (NOAC), inhibitors of factor IIa or Xa, are expected to be widely used for the treatment of venous thromboembolic disease, or in case of atrial fibrillation. Such anticoagulant treatments are known to be associated with haemorrhagic complications. Moreover, it is likely that such patients on long-term treatment with NOAC will be exposed to emergency surgery or invasive procedures. Due to the present lack of experience in such conditions, we cannot make recommendations, but only propose management for optimal safety as regards the risk of bleeding in such emergency conditions. In this article, only dabigatran and rivaroxaban were discussed. For emergency surgery at risk of bleeding, we propose to dose the plasmatic concentration of drug. Levels inferior or equal to 30. ng/mL for both dabigatran and rivaroxaban, should enable the realization of a high bleeding risk surgery. For higher concentration, it was proposed to postpone surgery by monitoring the evolution of the drug concentration. Action is then defined by the kind of NOAC and its concentration. If the dosage of the drug is not immediately available, proposals only based on the usual tests, PT and aPTT, also are presented. However, these tests do not really assess drug concentration or bleeding risk. In case of severe haemorrhage in a critical organ, it is proposed to reduce the effect of anticoagulant therapy using a nonspecific procoagulant drug (activated prothrombin concentrate, FEIBA, 30-50. U/kg, or non-activated 4-factors prothrombin concentrates 50. U/kg). For any other type of severe haemorrhage, the administration of such a procoagulant drug, potentially thrombogenic in these patients, will be discussed regarding concentration of NACO and possibilities for mechanical haemostasis. © 2013 Société française d'anesthésie et de réanimation (Sfar).
Dessap A.M.,Service de Reanimation Medicale |
Dessap A.M.,University Paris Est Creteil |
Dessap A.M.,French Institute of Health and Medical Research |
Deux J.-F.,Service dImagerie Medicale |
And 23 more authors.
American Journal of Respiratory and Critical Care Medicine | Year: 2011
Rationale: The pathophysiology of acute chest syndrome (ACS) in patients with sickle cell disease is complex, and pulmonary artery thrombosis (PT) may contribute to this complication. Objectives: To evaluate the prevalence of PT during ACS using multidetector computed tomography (MDCT). Methods: We screened 125 consecutive patients during 144 ACS episodes. One hundred twenty-one MDCTs (in 103 consecutive patients) were included in the study. Measurements and Main Results: Twenty MDCTs were positive for PT, determining a prevalence of 17% (95% confidence interval, 10-23%). Revised Geneva clinical probability score was similar between patients with PT and those without. D-dimer testing was very often positive (95%) during ACS. A precipitating factor for ACS was less frequently found in patients with PT as compared with those without. Patients with PT exhibited significantly higher platelet counts (517 [273-729] vs. 307 [228-412] 10 9/L, P < 0.01) and lower bilirubin (28 [19-43] vs. 44 [31-71] mmol/L, P < 0.01) levels at the onset of ACS as compared with others. In addition, patients with PT had a higher platelet count peak (537 [345-785] vs. 417 [330-555] 10 9/L, P = 0.048) and smaller bilirubin peak (36[18-51] vs. 46 [32-83] μmol/L, P = 0.048) and lactate dehydrogenase peak (357 [320-704] vs. 604 [442-788] IU/L, P = 0.01) during hospital stay as compared with others. Conclusions: PT is not a rare event in the context of ACS and seems more likely in patients with higher platelet counts and lower hemolytic rate during ACS. Patients with sickle cell disease presenting with respiratory symptoms suggestive of ACS may benefit from evaluation for PT.
PubMed | Laboratoire dHemostase, Center Hemophilie, Paris-Sorbonne University, University Paris - Sud and University of Paris Descartes
Type: Journal Article | Journal: JCI insight | Year: 2016
von Willebrand disease type 2B (VWD-type 2B) is characterized by gain-of-function mutations of von Willebrand factor (vWF) that enhance its binding to platelet glycoprotein Ib and alter the proteins multimeric structure. Patients with VWD-type 2B display variable extents of bleeding associated with macrothrombocytopenia and sometimes with thrombopathy. Here, we addressed the molecular mechanism underlying the severe macrothrombocytopenia both in a knockin murine model for VWD-type 2B by introducing the p.V1316M mutation in the murine
Vancraeyneste H.,University of Lille Nord de France |
Vancraeyneste H.,French Institute of Health and Medical Research |
Charlet R.,University of Lille Nord de France |
Charlet R.,French Institute of Health and Medical Research |
And 16 more authors.
American Journal of Physiology - Heart and Circulatory Physiology | Year: 2016
Platelets are capable of binding, aggregating, and internalizing microorganisms, which enhances the elimination of pathogens from the blood. The yeast Candida albicans is a pathobiont causing life-threatening invasive infections. Its cell wall contains β-1,3 glucans that are known to trigger a wide range of host cell activities and to circulate during infection. We studied the effect of β-1,3 glucan fractions (BGFs) consisting of diglucosides (Glc2), tetraglucosides (Glc4), and pentaglucosides (Glc5) on human platelets, their mechanisms of action, and their possible impact on host defenses. The effect of BGFs on the coagulation process was determined by measuring thrombin generation. Platelets pretreated with BGFs were analyzed in terms of activation, receptor expression, aggregation, and adhesion to neutrophils and to C. albicans. The results show that BGFs affected the endogenous thrombin potential in a concentration-dependent manner. For platelet activation, BGFs at a low concentration (2 μmol/l) reduced ATP release and prevented the phosphorylation of protein kinase C. BGFs diminished the expression of P-selectin and the activation of αIIbβ3. BGFs decreased platelet aggregation and the interaction between thrombin-stimulated platelets and neutrophils, fibrinogen, and C. albicans. GLc5 decreased ATP release and TGF-β1 production in response to TLR4 upregulation in thrombin-stimulated platelets, but TLR4 blockage abolished the effect of BGFs on platelets. This study provides evidence that fungal pentaglucosides modulate platelet activity mediated via TLR4 stimulation and reduce platelet-neutrophil interaction. © 2016 the American Physiological Society.
Guignant C.,Laboratoire dImmunologie |
Guignant C.,University of Lyon |
Venet F.,Laboratoire dImmunologie |
Venet F.,University of Lyon |
And 12 more authors.
Intensive Care Medicine | Year: 2013
Purpose: A new pathway of three protein tyrosine kinase receptors, namely, the TAM receptor family [Tyro-3, Axl and Mer tyrosine kinase (MerTK)], has recently been described to negatively control immune responses. The objective of this prospective, observational, clinical study was to investigate the expression patterns of TAM receptors in circulating white blood cells collected from patients with septic shock. Methods: The expression of TAM receptors was measured by flow cytometry in circulating leukocytes from patients with septic shock sampled on days (D) 1-2 (n = 47) and D3-4 (n = 37) after the onset of shock, severe trauma patients at D1-2 after trauma (n = 51) and healthy individuals (n = 23). Results: On D1-2 after injury, MerTK was overexpressed in monocytes and neutrophils collected from patients with septic shock in comparison with those collected from healthy volunteers and trauma patients. This phenomenon was also observed for mRNA. Conversely, the expression of Tyro-3 and Axl was higher in monocytes from trauma patients versus healthy volunteers or those in septic shock. MerTK expression between D1-2 and D3-4 remained elevated in patients suffering from septic shock who died or developed an intensive care unit-acquired infection, whereas it decreased in patients who recovered uneventfully. This in vivo observed expression pattern was reproduced ex vivo after the incubation of healthy volunteer cells with plasma from septic shock or trauma patients. Conclusions: MerTK expression in circulating innate immune cells is increased in patients with septic shock in comparison with healthy volunteers and trauma patients. Persistent MerTK overexpression after septic shock is associated with adverse outcome. The role of this family of receptors in the pathophysiology of injury-induced immune dysfunctions deserves to be specifically investigated. © 2013 Springer-Verlag Berlin Heidelberg and ESICM.
PubMed | Service de Parasitologie Mycologie, Plateforme dInteraction Moleculaire, Laboratoire dHemostase, Cleveland Clinic and 2 more.
Type: Journal Article | Journal: American journal of physiology. Heart and circulatory physiology | Year: 2016
Platelets are capable of binding, aggregating, and internalizing microorganisms, which enhances the elimination of pathogens from the blood. The yeast Candida albicans is a pathobiont causing life-threatening invasive infections. Its cell wall contains -1,3 glucans that are known to trigger a wide range of host cell activities and to circulate during infection. We studied the effect of -1,3 glucan fractions (BGFs) consisting of diglucosides (Glc2), tetraglucosides (Glc4), and pentaglucosides (Glc5) on human platelets, their mechanisms of action, and their possible impact on host defenses. The effect of BGFs on the coagulation process was determined by measuring thrombin generation. Platelets pretreated with BGFs were analyzed in terms of activation, receptor expression, aggregation, and adhesion to neutrophils and to C. albicans The results show that BGFs affected the endogenous thrombin potential in a concentration-dependent manner. For platelet activation, BGFs at a low concentration (2 mol/l) reduced ATP release and prevented the phosphorylation of protein kinase C. BGFs diminished the expression of P-selectin and the activation of IIb3 BGFs decreased platelet aggregation and the interaction between thrombin-stimulated platelets and neutrophils, fibrinogen, and C. albicans GLc5 decreased ATP release and TGF-1 production in response to TLR4 upregulation in thrombin-stimulated platelets, but TLR4 blockage abolished the effect of BGFs on platelets. This study provides evidence that fungal pentaglucosides modulate platelet activity mediated via TLR4 stimulation and reduce platelet-neutrophil interaction.
Rissoul K.,Laboratoire dHemostase |
Madani M.,Groupement Hospitaller Est |
Nougier C.,Laboratoire dHemostase |
Rugeri L.,Laboratoire dHemostase |
Negrier C.,Laboratoire dHemostase
Annales de Biologie Clinique | Year: 2010
Heparin-induced thrombocytopenia (HIT) is a severe complication of heparin therapy caused by an antibody against heparin/Platelet Factor 4 (PF4) complex. It complicates the treatment with unfractionated heparin (UFH). The aim of the study was to assess the interest of using confirmatory test in ELISA with use of high concentration of heparin (100 UI/mL) in patients (n = 15) with discordance between platelet activation test and ELISA test. We obtained a rate inhibition higher than 50% in 86% of patients was observed. We conclude that inclusion of the high heparin confirmatory procedure in ELISA demonstrate the dependant heparin character of the antibodies but does not improve diagnostic specificity. In addiction a 2-fold increase in final test cost is observed.
Jourdy Y.,Laboratoire dhemostase |
Le Quellec S.,Laboratoire dhemostase |
Nougier C.,Laboratoire dhemostase
Immuno-Analyse et Biologie Specialisee | Year: 2013
Beside structural and physiological ADAMTS 13 data, this paper points out the main features of ADAMTS 13 assays and their interest in several clinical situations. © 2013 .
Floccard B.,Hospices Civils de Lyon |
Rugeri L.,Laboratoire dHemostase |
Faure A.,Hospices Civils de Lyon |
Denis M.S.,Hospices Civils de Lyon |
And 10 more authors.
Injury | Year: 2012
Purpose: Amongst trauma patients, early coagulopathy is common on hospital admission. No studies have evaluated the initial coagulation status in the pre-hospital setting. We hypothesise that the coagulopathic process begins at the time of trauma. We studied the on-scene and on hospital arrival coagulation profile of trauma patients. Methods: Prospective, observational study investigating the on-scene coagulation profile and its time course. We studied 45 patients at the scene of the accident, before fluid administration, and on hospital admission and classified their coagulopathy using the International Society on Thrombosis and Haemostasis score during a 2-month period. Prothrombin time, activated partial thromboplastin time, fibrinogen concentration, factors II, V and VII activity, fibrin degradation products, antithrombin and protein C activities, platelet counts and base deficit were measured. Results: The median injury severity score was 25 (13-35). On-scene, coagulation status was abnormal in 56% of patients. Protein C activities were decreased in the trauma-associated coagulopathy group (p =.02). Drops in protein C activities were associated with changes in activated partial thromboplastin time, prothrombin time, fibrinogen concentration, factor V and antithrombin activities. Only factor V levels decreased significantly with the severity of the trauma. On hospital admission, coagulation status was abnormal in 60% of patients. The on-scene coagulopathy was spontaneously normalised only in 2 patients whereas others had the same or a poorer coagulopathy status. All parameters of coagulation were significantly abnormal comparing to the on-scene phase. Decreases in protein C activities were related to the coagulation status (p <.0001) and changes in other coagulation parameters. Patients with base deficit ≤-6 mmol/L had changes in antithrombin, factor V and protein C activities but no significant coagulopathy. Conclusion: Coagulopathy occurs very early after injury, before fluid administration, at the site of accident. Coagulation and fibrinolytic systems are activated early. The incidence of coagulopathy is high and its severity is related to the injury and not to hypoperfusion. © 2010 Elsevier Ltd. All rights reserved.