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Since the advent of transgenesis techniques, the mouse model has become the model par excellence in research laboratories, making it possible to model various pathologies or better understand the functions of numerous proteins, in a controlled genetic environment. The resulting challenge has been to develop methods for assessing various phenotypes in a small model such as the mouse. Hemostasis is no exception, and procedures adapted to the measurement of bleeding have emerged. Some of these procedures, and in particular the most frequently used, will be detailed in this review. These experimental models have proliferated in response to the phenotypic heterogeneity of transgenic mice developed in the field of coagulation. We have endeavored to present an example of this heterogeneity, focusing on the mouse models of Willebrand disease that exist today. Indeed, a large number of Willebrand disease models are currently available, attempting as best they can to reproduce the most varied aspects of this extremely polymorphic pathology. These models will be discussed, taking stock of their respective contributions either to improving our knowledge of pathophysiological mechanisms, or as pre-clinical models for the evaluation of new therapies. [ABSTRACT FROM AUTHOR]

Vascular access through the distal radial artery, an innovative method for accessing the coronary arteries, is gaining popularity due to its substantial benefits, including a reduction in vascular complications and enhanced comfort for both the patient and the operator. The distal radial puncture technique was introduced in 1982 for anesthesia and adopted in interventional cardiology in the late 1990s. Researchers have published promising results, supporting the efficacy and safety of this method. This technique offers several advantages, the most interesting being the preservation of the proximal radial artery, the comfort of the patient and the operator, and a reduced hemostasis time favoring the ambulatory aspect of the procedures. However, a learning curve is required, but it is comparable to the one observed during the first use of the proximal radial artery. [ABSTRACT FROM AUTHOR]

A2-macroglobulin (A2M) is an antiproteinase that plays different roles in hemostasis. A2M is a homo-tetrameric glycoprotein of high molecular weight highly conserved throughout evolution. Proteinase inhibitor activity of A2M is possible via a unique cage structure able to trap proteinase without having any direct inhibition regarding enzymatic activity. Clearance of trapped proteinase is achieved through A2M binding to the low-density lipoprotein receptor-related protein 1: LRP1. A2M synthesis is controlled by pro-inflammatory cytokines and increases in several chronic or acute inflammatory diseases and also varies with age. A2M can trap several proteinases involved in both coagulation and fibrinolysis, thus acting as a trigger and inhibitor of hemostasis. A2M is able to inhibit thrombin, factor Xa, activated protein C, plasmin, tissue-plasminogen activator and urokinase. A2M is usually put apart in hemostasis balanced regulation. A2M plasma concentration are differently regulated during inflammatory-related diseases. It can also neutralize cytokines that are known to modify hemostasis as well. In this review, we propose to summarize known functions of A2M focusing on the roles of this antiproteinase in hemostasis and thrombosis. [ABSTRACT FROM AUTHOR]

The standard hemostasis workup [quick time (QT), and activated partial thrombin time (APTT)] is very commonly prescribed but its interpretation is often difficult for practitioners who are not specialized in hemostasis. Here, we review the principles of the diagnostic approach to these tests. Only a very basic knowledge of the coagulation cascade is necessary to identify which clotting factor tests to prescribe and to interpret the results. Deficiency in several clotting factors suggests liver dysfunction, disseminated intravascular coagulation (DIC) or vitamin K deficiency. If a single factor is deficient, we review the different causes of acquired deficiencies and briefly discuss the characteristics of the different congenital defects, which generally require specialized management. Lupus anticoagulant is a common and generally benign cause of prolonged APTT to be aware of, which is not related to a hemorrhagic risk. A good knowledge of the diagnostic approach to abnormal QT or APTT generally allows the resolution of the most common situations., (Copyright © 2024 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Edoxaban is a direct oral anticoagulant available in Europe but not in France. Given the high tourist traffic in France, understanding the pharmacology of edoxaban and the availability of its laboratory testing seemed crucial in emergency situations. The aim of this work was to describe the methodology for measuring the anti-Xa activity of edoxaban, highlighting pre-analytical and analytical aspects, along with essential clinico-biological data for therapeutic guidance. The analysis was performed using the chromogenic method on the STAR-Max analyzer, with the STA®-Liquid ANTI-Xa kit (Diagnostica Stago®). Anti-Xa Edoxaban level measurement has a detection limit of 15 ng/mL, a quantification limit of 20 ng/mL and a linearity limit of 400 ng/mL. Repeatability, intermediate precision, accuracy, and measurement uncertainty studies were conducted to assess method performance, meeting quality requirements. The comparison between two STAR-Max® analyzers showed excellent results with linear regression and a low bias with good precision and no loss of dispersion regardless of edoxaban levels. In conclusion, although the measurement of edoxaban level may be rarely necessary in clinical practice, its implementation is straightforward. The availability of edoxaban in neighboring countries, underscores the importance of having its measurement available in hospital laboratories.

Copyright of Annales Françaises de Médecine d'Urgence is the property of John Libbey Eurotext Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Résumé: Les afibrinogénémies sont des pathologies héréditaires exceptionnelles dont le risque hémorragique est majeur. Leur prise en charge et les complications peuvent être complexes car le fibrinogène, en dehors de son rôle dans la coagulation, a un rôle dans l'hémostase et la thrombose et a de nombreuses fonctions pléiotropes dans la cicatrisation, l'inflammation, etc. Afibrinogenemias are exceptional hereditary pathologies whose hemorrhagic risk is major. Their management and complications can be complex because fibrinogen, apart from its role in coagulation, has a role in hemostasis and thrombosis and has many pleiotropic functions in healing, inflammation, etc. [ABSTRACT FROM AUTHOR]

Résumé: Le purpura thrombotique thrombocytopénique (PTT) est une forme particulière de microangiopathie thrombotique résultant d'un déficit fonctionnel sévère en ADAMTS13 (pour a disintegrin and metalloprotease with thrombospondin type I repeats-13), la protéase spécifique de clivage du facteur Willebrand (VWF). L'accumulation de multimères de haut poids moléculaire de VWF hyperadhésifs aux plaquettes conduit à la formation spontanée de microthrombi dans la microcirculation, accompagnée d'une thrombopénie périphérique et d'une anémie hémolytique mécanique. Le PTT est très majoritairement une maladie acquise, le plus souvent auto-immune (PTTi) mais peut également être congénital (PTTc) et lié à des mutations délétères bialléliques du gène ADAMTS13 (syndrome d'Upshaw-Schulman). Le PTT évolue par poussées entrecoupées de rémissions, avec un risque de rechute nécessitant un suivi au long cours. Le PTT est idiopathique dans 50 % des cas, mais il peut également compliquer des contextes physiologiques ou pathologiques (grossesse, maladie auto-immune, infection, néoplasie ou greffe). Le PTT est une pathologie dont le diagnostic et la prise en charge ont drastiquement changé au cours des 30 dernières années, principalement en raison de l'avancée des connaissances sur le couple VWF/ADAMTS13. La PTT est une urgence thérapeutique, et le diagnostic présomptif peut être posé par des scores de probabilité clinicobiologique (French Score, PLASMIC Score). Le diagnostic de certitude repose toutefois sur la mesure de l'activité d'ADAMTS13, attendue effondrée (< 10 %). La confirmation biologique ne doit en aucun cas retarder la prise en charge, en particulier l'instauration d'une plasmathérapie substitutive permettant l'apport d'ADAMTS13 exogène, pierre angulaire du traitement de la phase aiguë du PTT. Les traitements immunomodulateurs, notamment le rituximab (anticorps monoclonal anti-CD20), sont également indiqués dans le PTTi. Enfin, le caplacizumab, un nanocorps dirigé contre le domaine A1 du VWF, a récemment rejoint l'arsenal thérapeutique après des résultats très satisfaisants en termes de diminution de la morbimortalité, d'après les résultats d'essais cliniques internationaux. Une ADAMTS13 recombinante est actuellement en cours d'évaluation, avec des résultats préliminaires prometteurs. Des outils innovants d'exploration de l'auto-immunité anti-ADAMTS13 émergent : la conformation d'ADAMTS13 et la cartographie des anticorps anti-ADAMTS13. Ces outils pourraient permettre l'identification de sous-groupes de patients de sévérités variables et ainsi conduire à leur stratification thérapeutique. Thrombotic thrombocytopenic purpura (TTP) is a specific form of thrombotic microangiopathy arising from a severe functional deficiency of ADAMTS13, the specific von Willebrand factor (VWF) cleaving protease. This defect leads to the accumulation of hyperadhesive VWF high molecular weight multimers and to the spontaneous formation of microthrombi in the microcirculation, accompanied by peripheral thrombocytopenia and mechanical hemolytic anemia. TTP is mainly an acquired disease, most often autoimmune (iTTP) but can also be inherited (cTTP) when deleterious bi-allelic mutations are found in the ADAMTS13 gene (Upshaw-Schulman syndrome). TTP is a relapsing-remitting disease requiring long-term follow-up. TTP is either idiopathic (50%) or associated to a physiological or pathological context such as pregnancy, autoimmune disease, infection, neoplasia or transplantation. TTP is a disease whose diagnosis and management have changed dramatically over the last 30 years, mainly due to break-throughs in the understanding of the VWF/ADAMTS couple. TTP is a therapeutic emergency, and can be detected by clinical prediction scores (French Score, PLASMIC Score); however, the formal diagnosis relies on the measurement of ADAMTS13 activity, which is expected to be <10 IU/dL. Biological confirmation should not delay management, particularly the initiation of plasma replacement therapy to provide exogenous ADAMTS13, which is the cornerstone of treatment in the acute phase of TTP. Immunomodulatory therapies, like rituximab (monoclonal antibody to CD20) are also recommended in iTTP. Finally, caplacizumab, a monoclonal antibody targeting the A1 domain of VWF, has recently joined the therapeutic options after very satisfactory results in terms of reduction of morbidity and mortality according to international clinical trials. A recombinant ADAMTS13 is currently being evaluated with promising preliminary results. Innovative tools to explore anti-ADAMTS13 autoimmunity are emerging: ADAMTS13 conformation and anti-ADAMTS13 antibody epitope-mapping. These tools may allow the identification of subgroups of patients of varying severity and consequently lead to their therapeutic stratification. [ABSTRACT FROM AUTHOR]

Combined deficiency of clotting factor V and factor VIII (DF5F8) is a congenital autosomal recessive disorder. This study involved a family of four children born to consanguineous parents. The eldest daughter was referred for assessment of activated partial thromboplastin time and prothrombin time associated with hemorrhagic manifestations. Coagulation factor dosing showed combined deficiency of factor V and factor VIII as well as normal levels of other coagulation factors. DF5F8 was detected in two girls and a boy. Two protein coding genes LMAN1 (lectin, mannose binding 1) and MCFD2 (multiple coagulation factor deficiency2) were involved in the intracellular passage of Factor V and Factor VIII, including some mutations which caused deficiency of Factor V and VIII. The diagnosis of DF5F8 is routinely possible, especially in patients born to consanguineous parents with a suggestive clinico-biological condition. [ABSTRACT FROM AUTHOR]

The lack of quality control for patient point-of-care (POC) INR devices is an issue that has led the French health authorities to make recommendations: a laboratory INR (lab INR) has to be performed at the same time as the POC INR every six months. However, the differences observed between the two INRs, POC and lab INRs, are not necessarily due to a failure of the POC INR device. We present here a review of the different causes of discrepancies between INR results, which are the basis of the proposals of the Groupe français d'études sur l'hémostase et la thrombose (GFHT) on the management of lab and POC INR discrepancies. Pre-analytical conditions may account for discrepancies (sampling, transport and storage conditions), as well as analytical factors (mainly the nature of the thromboplastin used) and the clinical context (inflammatory or autoimmune diseases, polycythaemia...). The interpretation of INR discrepancies is not always easy and these proposals aim at standardizing the procedure to be followed in order to make the most appropriate decision for the patient. [ABSTRACT FROM AUTHOR]

In the absence of interventional endoscopy the treatment of upper digestive hemorrhage a the brazzaville university hospital is only medicinal. Objective of this work was to identify risk factors for upper gastrointestinal bleeding by conducting a retrospective case-type study conducted over a period of 2 years. The 180 patients included for upper digestive hemorrhage were divided into 2 groups accordind to their progressive modality: deceaded patients (cases) and non-deceased patients (controls). Risk factors for mortality were studied by logistic regression. The mortality linked to upper gastrointestinal bleedind was 36.6%, the risk factors for death were age between 30 and 60 with an OR of 9.79; male (OR of 2.03); late hospitalization over 24 hours (OR of 6.30); blood transfusions (OR of 3.5). The protective factors were hemoglobin greater 7 g/dL (OR of 0.28); treatment by proton pump inhibitors (OR of 0.36). In conclusion, reducing the still high mortalty rate in our country requires taking into account the identified risque factors and aquiring endoscopic hemostasis equipement. [ABSTRACT FROM AUTHOR]

Résumé: L'infection respiratoire causée par le coronavirus 2 (Sars-CoV-2), maintenant nommée Covid-19 (pour coronavirus disease 2019), a été qualifiée de pandémie en 2020. L'infection par le Sars-CoV-2 peut conduire à une réponse immunitaire inadaptée, et en particulier à une amplification de la réponse inflammatoire responsable d'une aggravation clinique chez 5 à 10 % des patients atteints de Covid-19. Les patients qui présentent une pneumonie sévère sont susceptibles de développer une hypoxémie nécessitant une assistance ventilatoire invasive ainsi que des complications thrombotiques macrocirculatoires et/ou microcirculatoires. Coronavirus disease 2019 (Covid-19), a severe acute respiratory syndrome caused by coronavirus 2 (Sars-CoV-2), has now spread to all continents. About 5-10 % of Covid-19 patients require intensive care unit admission and mechanical ventilation. Critically ill Covid-19 patients are prone to develop hypoxia, excessive inflammation and frequent thrombotic manifestations affecting both the macrocirculation and the microcirculation. [ABSTRACT FROM AUTHOR]

We discuss four topics among the angiology and hemostasis studies of importance in 2023. The BASIL-2 study provides new data for the management of chronic limb-threatening ischemia by comparing surgical and endovascular treatment. The new classification of antiphospholipid antibody (aPL) syndrome integrates new clinical elements and gives a different weight among the isotype and titer of aPL. Concizumab, an antibody targeting the tissue factor pathway inhibitor, broadens the therapeutic arsenal for hemophilia A and B as evidenced by the results of the EXPLORER 7 study. The PREVENT-CLOT and CASTING study focus on the prevention of thrombosis after trauma, by testing the role of aspirin or the lack of thromboprophylaxis, respectively., Competing Interests: Le Pr P. Fontana a reçu un soutien financier pour des congrès de Sobi et NovoNordisk. Les autres auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Introduction: Snakebite envenomation is a major public health issue in Sub-Saharan Africa (SSA). Antivenoms are the only etiological treatment. However, the dose recommended by the manufacturer (2 vials renewed every 2 hours in case of persistent bleeding) is usually not applied due to the high cost which is borne only by the patient. Based on clinical presentation, we evaluated the administration of a single vial on admission (instead of 2 vials), which corresponds to the therapeutic protocol used in current practice in most health centers in Benin and beyond in SSA. Renewal of antivenom followed manufacturer's recommendation., Material and Method: The study took place in a first referral hospital in Tanguiéta, North Benin. All envenomed patients received a slow intravenous vial of Inoserp ® Pan-Africa (IPA) upon arrival. A clinical assessment identical to that of inclusion was carried out 2, 4, 6, 12 and 24 hours later to assess the tolerance and efficacy of the IPA, as well as the need to readminister the antivenom. The occurrence, persistence or worsening of clinical hemorrhages or neurological disorders, the latter reflecting envenomation by elapids, systematically led to the injection of 2 or 4 vials of IPA, respectively. Signs of intolerance were sought before and after each administration of antivenom, then 2 weeks to 1 month after treatment, in order to estimate the incidence of adverse effects attributable to the antivenom. Efficacy of IPA was assessed by cessation of bleeding and/or normalization of whole blood coagulation test (WBCT) within 24 hours of initial administration., Results: The study took place from July 31 to October 31, 2019. We received 53 cases of snakebites of which 43 were included. The median age was 21 [IQR: 18-31] years and the sex ratio (M/F) was 1.5. Farmers were the majority (48%). The median time to admission was 1 [IQR: 0-2] day. On admission, 32 patients (74%) presented hemostasis disorders marked by bleeding and/or abnormal WBCT. None of the patients showed neurological symptoms. The median time to normalization of WBCT was 24 [IQR: 4-72] hours. The median time to stop bleeding was 6 [IQR: 4-12] hours. In 3 of the 11 patients whose bleeding had stopped at H2, a recurrence occurred within the following 24 hours. In addition, 3 patients presented with late bleeding 24 hours after admission. Two patients (5%) died as a result of envenomation., Discussion/conclusion: The simplified protocol represents a significant saving in the number of vials used, i.e. 1.8±0.4 vials per patient instead of the 2.4±0.2 which would have been necessary in these same patients treated according to the standard protocol (p = 2.6·10 -4 ). However, in comparison with the results obtained during the previous clinical study, the cessation of bleeding is delayed, as is the normalization of the WBCT at the different follow-up times. In addition, the number of re-administrations of antivenom after H2 is higher in the light protocol than in the standard one, respectively 13 patients out of 43 treated versus 4 patients out of 59 (p = 0.006). There was no significant difference between the incidence of signs of early antivenom intolerance in this study compared to the previous one (16% and 11%, respectively; p = 0.79). This delay can put up to a third of patients at risk of complications. Despite its effectiveness and the antivenom savings made, it does not seem reasonable to recommend it., (Copyright © 2023 SFMTSI.)

The study was performed on 109 osteoarthritis patients who underwent hip joint endoprosthetics; the effect of age on changes in hemostasis system, blood loss level and deep veins thrombosis development in the background of standard prevention with low-molecular heparins were studied. Before the surgery, it was determined that 56 elderly patients (60.3 ± 6.4 years) compared to 53 middle-aged patients (41.8 ± 6.8 years) had a significantly higher initial and postoperative endothelial dysfunction, higher fibrin formation and lower anticoagulant potential; however, it was found that on the background of pharmacological anticoagulant therapy the changes in the hemostasis functioning in elderly patients did not lead to an increase of either blood loss or the number of thromboses.

Von Willebrand factor (vWF) is a glycoprotein which plays an important role in hemostasis. Its quantitative or qualitative deficit results in von Willebrand's disease (vWD). The study aims to update the current understanding of the distribution of vWF rates in Moroccan pregnant women and their variability in function of the ABO blood group. We conducted a cross-sectional study of 390 pregnant women from the Rabat-Salé-Kenitra region. Sample size was calculated on the basis of a prevalence of 1%, corresponding to the global prevalence of vWD with a margin of error of 5% and a confidence level of 95%. There were 317 cases (81.28%) of elevated vWF levels (> 160%) out 390 pregnant women. The levels of factor VIII (FVIII) varied in parallel in a significant way (p < 0.001) with the levels of vWF (Pearson's r 0,597). The distribution of the ABO blood groups has had an influence on the level of vWF with a significant difference (p < 0.001) between the four groups: the lowest average level in the group O (188,54±57,02), followed by group A (203,19±54,46), then group AB (219±38,95) and finally group B (221,15±48,63). Our results confirm on the one hand an elevation of the levels of vWF during pregnancy and on the other hand the influence of ABO blood group on the levels of vWF. [ABSTRACT FROM AUTHOR]

Cardiac surgery with extracorporeal circulation (ECC) is usually associated with the loss of a significant amount of blood. Adequate prophylaxis against blood loss and good perioperative hemostasis are known as processes limiting postoperative bleeding. Until now, the need for platelets in patients operated with extracorporeal circulation in our Department has been compensated for by total blood transfusion or platelet concentrates collected from several donors. We here report our first experience with platelet concentrate collection by apheresis at the General Hospital in Douala. [ABSTRACT FROM AUTHOR]

Résumé Les anticoagulants oraux directs (AOD) sont l’objet d’un nombre croissant de prescriptions, représentant 50 % des nouvelles instaurations de traitement anticoagulant. Leur simplicité d’utilisation réside dans l’absence de surveillance biologique régulière, contrairement aux anti-vitamines K. Cependant, les situations au cours desquelles l’effet anticoagulant de ces molécules doit être évalué, plus ou moins urgemment, ne sont pas rares. La connaissance des mécanismes d’action, de la pharmacocinétique et des études ayant permis l’obtention des AMM sont des éléments indispensables à la compréhension des modalités de surveillance. Celle-ci peut se faire dans une certaine mesure à l’aide des tests standard et largement disponibles mais repose en réalité sur des tests spécifiques moins répandus. L’interprétation des résultats implique la maîtrise de tous les paramètres pré-analytiques, en particulier les renseignements cliniques. Des algorithmes décisionnels sont disponibles permettant une prise en charge optimale des malades. La mise à disposition d’antagonistes de ces molécules s’accompagnera à n’en pas douter d’une augmentation de leur prescription, de leur surveillance et des questions que l’ensemble nous pose. Direct oral anticoagulants prescription is continuously increasing, representing 50 % of anticoagulation drug initiation. In opposition with vitamin K antagonists, they seem easier to use, without requiring dose adjustment or biological monitoring. However, there still persist clinical situations requiring, with or without emergency, the correct assessment of patient coagulation state. Knowledge and understanding of their biological and pharmacokinetic properties as well as the design of studies conducted to get their approv al, is a key point to understand the whys and wherefores of their monitoring. To a certain extent, this monitoring can rely on routine laboratory tests, easy to perform and widely available. Nevertheless, accurate assessment is based on specific testing less available. Interpretation of these results requires a full control of pre-analytical points, especially clinical aspects. Algorithms are available, allowing the management of the patient based on both clinical and biological aspects. Antagonisms availability will increase DAO prescriptions as well as asking regarding their monitoring. [ABSTRACT FROM AUTHOR]

Dental management of patients who tend to develop a high risk of bleeding due to the use of anticoagulants is a challenge in the daily practice of professional dentists. Sufficient knowledge of the hemostasis mechanisms and optimization management of these patients are very important parameters. Incidentally, many recent studies have highlighted the possibility of practicing oral surgical procedures without interruption or reduction in dosage of vitamin K antagonists The aim of this paper is to discuss the various current guidelines and clinical approach to the management of patients receiving vitamin K antagonists scheduled to undergo dental surgery procedure. [ABSTRACT FROM AUTHOR]

Inherited platelet disorders (thrombocytopenia, functional defects or both) are rare and extremely heterogeneous with variable risk of spontaneous bleeding, but they are frequently diagnosed after haemorrhages following a surgical procedure or a trauma. Clinical studies focusing on these disorders are scarce due to their paucity, and thus they did not allow defining strong recommendations on the haemostasis treatment of these patients. On the basis of literature review and the experience of his members, the Reference Centre on inherited platelet disorders in France provides practical recommendations on the perioperative management, according to the type of underlying disease, to the bleeding risk associated to the invasive procedure, and to the clinical history of the patient. The indication and use of platelet concentrates and of various drugs i.e. tranexamic acid, desmopressin, recombinant factor VIIa, vonWillebrand factor concentrates, and thrombopoïetin receptor agonists are discussed in this text. [ABSTRACT FROM AUTHOR]

Résumé La balance hémostatique pédiatrique, qui est différente de celle des adultes, évolue au cours du développement, de la vie fœtale à l’âge adulte, particulièrement durant les premiers mois de la vie. Ce concept dynamique décrit initialement dans les années quatre-vingt, a été validé dans différents environnements techniques et est maintenant accepté par tous. Toutes les études démontrent qu’à la naissance, les taux de la plupart des facteurs et inhibiteurs de la coagulation sont diminués d’environ 50% par rapport aux adultes, les nouveau-nés prématurés ayant des taux plus faibles que les nouveau-nés à terme. Les taux adultes des différents paramètres de d’hémostase sont généralement atteints entre quelques mois et un an, voir à la puberté pour certains. Si la tendance globale est constante à travers les études, des différences en valeurs absolues peuvent être notées selon les techniques utilisées. Aussi, le Sous-comité Hémostase Périnatale et Pédiatrique du Comité Scientifique et de Standardisation de l’ISTH recommande de définir ses propres valeurs usuelles dans son propre environnement technique. La compréhension de ce concept dynamique d’hémostase pédiatrique est fondamentale pour assurer une prévention, un diagnostic et un traitement approprié des maladies hémorragiques et thrombotiques. Summary The pediatric hemostatic balance, which is different from that in adults, is an evolving process as the hemostatic system changes and matures throughout the time from fetal to adult life, particularly in the early months of life. The concept of developmental hemostasis was confirmed by several studies evaluating different patients’ population in various technical conditions. All demonstrated that, at birth, the plasma levels of coagulation factors were around half that found in adults, the pre-term infants having lower levels than full-term infants. Adult values were reached between a few months of age and up to above 16 years for specific parameters. If the global trends are consistent across the studies, differences in absolute values could be demonstrated that are likely due to differences in the reagents and/or the instruments used. Accordingly, it is recommended by the Perinatal and Pediatric Haemostasis Subcommittee of the Scientific and Standardization Committee of the ISTH for each laboratory to define the age-dependent reference ranges by using its own technical condition. The understanding of that concept of developmental hemostasis, which is now universally accepted, is critical to ensure optimal prevention, diagnosis, and treatment of thrombotic and hemorrhagic diseases in children. [ABSTRACT FROM AUTHOR]

Polymorphonuclear cells (PMNC) are key cells of immunity. The production of Neutrophil Extracellular Traps (NETs) isconsecutive toPMNCactivation,which leads to the release of long DNA fragments decorated with highly diversified proteins. NETs have initially been described in infection control processes since they can trap and kill extra-cellular pathogens.NETs can also contribute to immunothrombosis, a pathogenic process involving the innate immune system and leading to thrombus formation. Actually, NETs were shown to be implicated in all main processes of hemostasis. They enhance platelet activation and aggregation, and promote the coagulation cascade by activating the contact pathway. NETs also inhibit physiologic inhibitors, and form a three-dimensional scaffold that helps fibrin clot formation. NETs also seemto confer fibrin clot resistance to fibrinolysis. Animal models suggested an implication of NETs in venous thrombosis, and in arterial thrombotic diseases such as atherosclerosis or ischemic stroke. Even if evidence for a critical role of NETS ismore limited in human pathology, new targeted therapies could represent an alternative approach in specific diseases. [ABSTRACT FROM AUTHOR]

The Lyon Hospitals Board (HCL) hemostasis laboratory has shifted from a frequentist to a long-term Bayesian approach to IQC results management, using the Hemohub® software of the Werfen corporation, which hosts the requisite Bayesian tools. IQC plans based on supplier specifications proved effective in managing analytic risk in line with the ISO 15189 standard. Long-term Hemohub® control and monitoring has been validated by acceptable feedback from the EQA organization used by the hemostasis community.

In this article, we have selected four topics that particularly caught our attention during the year 2022, and which are related to anticoagulation, its bleeding complications, and hemophilia. Thus, we discuss the issue of the treatment with rivaroxaban of atrial fibrillation associated with rheumatic valvulopathy, which has been studied in a randomized trial, the intensity of thromboprophylaxis in COVID outpatients and inpatients, and the bleeding risk of anticoagulation in patients with cerebral tumors. Finally, recent data on gene therapy in severe hemophilia A, an upcoming treatment, are discussed., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Résumé Un monitorage répété et très rapide de l’hémostase en temps réel est indispensable dans certaines circonstances au chevet du patient par des examens de biologie médicale délocalisés (EBMD) pour diagnostiquer précocement une coagulopathie et mettre en oeuvre si cela est nécessaire des transfusions appropriées de produits sanguins. Ces EBMD réalisés sur sang total avec des dispositifs spécifiques sont surtout en France le temps de coagulation activé en chirurgie cardiaque (circulation extracorporelle et cathétérisme cardiaque) pour prévenir les hémorragies par surdosage d’héparine, la thromboélastométrie en chirurgie cardiaque également, dans les greffes de foie, les hémorragies sévères des polytraumatisés ou du post-partum. Enfin, il y a depuis longtemps dans de nombreux pays en Europe des dispositifs pour la détermination du ratio normalisé international (INR) chez les malades sous antivitamines K, en France pour seulement les enfants sous AVK, et parfois dans les services d’urgence. Ces EBMD sont en France sous la responsabilité du laboratoire de biologie médicale qui doit s’assurer de la justification de leur usage et qui doit suivre les recommandations pour l’accréditation des laboratoires suivant la norme EN ISO 22870. Summary A repeated and very fast monitoring in real time of the process of coagulation is very important in some circumstances near the patient by point-of-care testing (POCT) in order to diagnose a coagulopathy at an early stage and to guide blood product replacement. These POCT in haemostasis, carried out on whole blood, are especially the activated clotting time in cardiac surgery, in cardiopulmonary bypass or cardiac catheterization, in order to prevent bleeding due to an excess of heparin, thromboelastometry in cardiac surgery, in orthotopic liver transplantation and in severe bleeding in trauma and post-partum. Finally for a long time in many countries in Europe POCT coagulometers are used for the determination of the International Normalized Ratio (INR) for patients under vitamin K antagonists (VKA), in France only for children under VKA, and sometimes in emergency units. These POCT are in France under the responsibility of the laboratory which must ascertain the justification of clinical need and which must conform to the recommendations for the accreditation of the laboratories according to the French norm EN ISO 22870. [ABSTRACT FROM AUTHOR]

Copyright of Biologie Aujourd'hui is the property of EDP Sciences and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Résumé: Le foie a un rôle prépondérant dans le maintien en équilibre de la balance hémostatique. L’altération des fonctions hépatiques impacte l’ensemble des étapes de l’hémostase : l’hémostase primaire, la coagulation plasmatique et la fibrinolyse. En effet, le foie synthétise la majorité des facteurs procoagulants, des molécules anticoagulantes ainsi que les protéines impliquées dans le processus de fibrinolyse. Son action d’élimination de ces mêmes molécules est tout aussi importante. Une maladie hépatique telle que la cirrhose a donc des répercussions hémostatiques potentiellement graves. La cirrhose entraîne une altération du tissu hépatique qui induit une modification des taux des différents acteurs de l’hémostase. Cependant, un état d’équilibre précaire s’installe. Les patients cirrhotiques ont longtemps été considérés comme naturellement « auto-anticoagulés » du fait de la baisse des taux de facteurs procoagulants et de l’allongement des tests classiques de la coagulation comme le temps de Quick (TQ) ou le temps de céphaline avec activateur (TCA). Cependant, les données épidémiologiques montrent que les patients cirrhotiques sont tout autant exposés aux complications thrombotiques qu’hémorragiques. Si les tests classiques de la coagulation ont un intérêt pour explorer le degré d’insuffisance hépatocellulaire chez le patient cirrhotique, ils sont incapables d’évaluer les variations combinées des taux de facteurs procoagulants et anticoagulants. Ces tests ne reflètent donc pas le véritable potentiel hémostatique des patients cirrhotiques et échouent à détecter les patients ayant un déséquilibre de la coagulation. Des tests globaux tels que la thrombinographie semblent se rapprocher du phénomène de la coagulation in vivo grâce à une mesure prolongée dans le temps du phénomène et une prise en compte de l’action des molécules anticoagulantes. Ce test met en évidence chez les patients cirrhotiques un phénotype reflétant une hypercoagulabilité. [Copyright &y& Elsevier]

Objective: The objective of our study was to identify the prognostic factors of death by scorpion envenomation in the region of Marrakech. Methods: We conducted a case-control study. It involved children hospitalized in the pediatric intensive care unit of the University Hospital of Marrakech after a scorpion envenomation between 1 October 2009 and 31 October 2012. An operating sheet was filled with the records of hospitalizations designed by the Poison Control Center of Morocco. Cases (n = 30) are represented by the children living in the area and who died during their hospitalization. For each case, we selected four witnesses among the survivors. A descriptive analysis, bi- and multivariate, was performed. Results: The median age was 5 years [2 months-14 years]. The M/F sex ratio was 1.5. The median delay between the bite and admission to the intensive care unit (TPP2) was 3 h 40 min [30 min-25 h]. Clinical signs commonly reported were vomiting (83%), priapism (72%) and sweating (70%). Biologically, leukocytosis, the hemostasis disorders, hyperglycemia and hyperuremia were statistically related to the death. Multivariate analysis showed that TPP2 > 5 h increased the risk of progressing to death five times, adjusting for age and vital distress (CI 95% 1.6-17). Conclusion: The upgrade of technical equipment and specialized personnel in the provincial resuscitation units are key elements to reduce TPP2, which is an important prognostic factor of death by scorpion envenomation in the Marrakech-Tensift-Al Haouz region. [ABSTRACT FROM AUTHOR]

Résumé: S’il apparaît qu’en France, trois types de plasma thérapeutique sont actuellement préparés, distribués et délivrés, bien davantage de plasmas thérapeutiques ayant le statut de produits sanguins labiles ou de médicaments dérivés du sang sont disponibles au niveau mondial. Pour un produit type – une même appellation – plusieurs procédés de production ainsi qu’une variété de machines ou de DMU concourant à sa production font qu’il y a en fait un grand nombre de produits finis différents qui peuvent de ce fait soit avoir des propriétés sensiblement distinctes (ou non) et/ou générer des effets indésirables différents (ou non également). Cette revue entend faire le point sur ces questions, de sorte à attirer l’attention sur les difficultés qu’il y a à comparer des données obtenues de façon différente dans des systèmes transfusionnels particuliers ; elle a pour objectif secondaire de dégager des pistes de réflexion pour la préparation future des plasmas thérapeutiques. [ABSTRACT FROM AUTHOR]

Résumé: Les nouveaux anticoagulants oraux (NACO), anti-IIa ou anti-Xa directs, sont destinés à être largement utilisés dans le traitement de la maladie thromboembolique veineuse ou dans la fibrillation atriale en remplacement des antivitamines K (AVK). Comme tout traitement anticoagulant, notamment aux doses dites ű curatives Ƈ, ils sont associés à un risque hémorragique spontané ou provoqué. De plus, une proportion non négligeable de patients traités sera confrontée à la nécessité d’un geste invasif en urgence. Compte tenu de l’absence d’antidote spécifique, les mesures à prendre doivent être définies dans ces situations. Le peu de données disponibles ne permet pas d’émettre des recommandations, mais seulement des propositions qui seront amenées à évoluer en fonction de l’expérience accumulée. Les propositions présentées dans cet article s’appliquent au dabigatran (Pradaxa®) et au rivaroxaban (Xarelto®), les données relatives à l’apixaban et à l’edoxaban étant encore trop peu nombreuses. Pour la chirurgie urgente à risque hémorragique, il est proposé de doser le taux plasmatique du médicament. Des taux inférieurs ou égaux à 30ng/mL, à la fois pour dabigatran et rivaroxaban, devraient permettre la réalisation d’une chirurgie à risque hémorragique élevé. Au-delà, il est convenu, dans la mesure du possible, de reporter l’intervention en surveillant l’évolution de la concentration du médicament. La conduite à tenir est alors définie selon le NACO et sa concentration. Si le dosage du médicament n’est pas disponible immédiatement, des propositions ű dégradées Ƈ sur la base de tests usuels, TP et TCA, sont présentées. Ces tests ne permettent cependant pas d’évaluer réellement ni la concentration de médicament, ni le risque hémorragique qui en dépend. En cas d’hémorragie grave dans un organe critique, il est proposé de réduire l’effet du traitement anticoagulant par l’utilisation d’un médicament procoagulant non spécifique en première ligne [concentrés de complexe prothrombinique activé (FEIBA® 30–50U/kg) ou non activé (CCP 50U/kg)]. En dehors de cette situation, pour tout autre type d’hémorragie grave, l’administration d’un médicament procoagulant, potentiellement thrombogène chez ces patients, sera discutée en fonction du taux de NACO et des possibilités d’hémostase mécanique. [ABSTRACT FROM AUTHOR]

Introduction: hemostasis hysterectomy is the radical treatment for postpartum hemorrhage. The purpose of this study is to identify risk factors, indications and complications of hemostasis hysterectomy and to determine factors influencing the types of approaches to hysterectomy., Methods: we conducted a monocentric descriptive and analytical retrospective study in the Department of Obstetrics and Gynecology at the Regional Hospital of Ben Arous from 2003 to 2019. Patients were classified according to the type of surgical treatment they received: total or subtotal hysterectomy., Results: seventy patients were included in the study. The rate of hemostasis hysterectomy was 1.3%. The average age of patients was 34.5 years (±5.1). Indications for hemostasis hysterectomy were dominated by placenta accreta (39% of cases; n=27), uterine inertia (34% of cases; n=24) and uterine rupture (16% of cases; n=11). Perioperative morbidity rate was 34 % (n=24). The most frequent complications were hemorrhagic shock (17%; n=12), disseminated intravascular coagulation (6%; n=4) and bladder lesions (6%; n=4). We reported six cases of maternal death, reflecting a rate of 8% (n=6). Subtotal hysterectomy was performed in 79% of patients (n=55) and 21% of women (n=15) underwent total hysterectomy. Placenta accreta was significantly associated with total hysterectomy group (aOR: 6.93, 95% CI: 1.07-44,80, p=0.042) and the average operation time was significantly shorter in subtotal hysterectomy group (aOR: 1.023; 95% CI: 1.009-1.03, p= 0.01)., Conclusion: hysterectomy is essential in certain patients with severe postpartum hemorrhage. Placenta accreta is the main indication for hysterectomy. Total hysterectomy is not associated with an increased risk of complications compared to subtotal hysterectomy., Competing Interests: Les auteurs ne déclarent aucun conflit d´intérêts., (Copyright: Idriss Abidi et al.)

Résumé: Les ménométrorragies sont fréquentes chez les adolescentes. Elles sont fonctionnelles dans la majorité des cas. Il convient d’éliminer une grossesse, des troubles de l’hémostase, en particulier la maladie de Willebrand qui est le trouble de coagulation le plus fréquent, et plus rarement une maladie chronique ou une endocrinopathie sous-jacente. L’évaluation est clinique (interrogatoire, score de Higham, évaluation du retentissement avec mesure de la pression artérielle) et biologique (en première intention : taux d’hCG, numération formule sanguine plaquettes (NFS), ferritine, taux de prothrombine, temps de céphaline activée). La prise en charge doit associer la correction de l’anémie en fonction de sa sévérité et l’arrêt des saignements. Le traitement repose sur la prescription d’agents anti-fibrinolytiques ou d’anti-inflammatoires non stéroïdiens (AINS) associés le plus souvent à un traitement hormonal, de type estroprogestatif oral ou progestatif oral cyclique. Les dysménorrhées primaires ou fonctionnelles affectent 40 à 90 % des adolescentes et représentent une source importante d’absentéisme scolaire. La prise en charge initiale repose sur un traitement d’épreuve par AINS ou par la prescription d’un traitement hormonal estroprogestatif en cas d’un souhait d’une contraception ou en cas d’inefficacité des AINS. Il est fondamental en cas de douleurs pelviennes chroniques persistantes malgré le traitement d’épreuve de rechercher une pathologie pelvienne sous-jacente, en particulier une endométriose qui devra être recherchée par la réalisation d’une IRM pelvienne. [ABSTRACT FROM AUTHOR]

Résumé: Les patients ayant une insuffisance hépatocellulaire présentent des altérations complexes de l'hémostase, certaines pouvant favoriser un saignement et d'autres étant de nature procoagulante. La résultante de ces anomalies allant dans des sens opposés ne peut pas être évaluée par les examens d'hémostase de routine (T. Quick, numération plaquettaire). Les perturbations de ces tests n'ont pas de valeur prédictive d'une complication hémorragique qui est le plus souvent liée à l'existence d'une hypertension portale. La correction systématique de ces anomalies par la transfusion de plasma frais congelé et/ou de concentrés de plaquettes pour prévenir un saignement est inappropriée et peut éventuellement être délétère. [ABSTRACT FROM AUTHOR]

Summary: The frequency of menometrorrhagia in adolescence is estimated at 2–5 %. The functional origin is the most common. Hemostasis abnormalities account for 20 % of cases, and they should be sought whenever there is a personal history of known or suggestive of hemostasis disorders (epistaxis, gingival bleeding, postoperative bleeding, bruising, etc.) or there is a family history of hemostasis disorders. Organic origins are rare, but these must be sought when the characteristics of bleeding point in this direction. The workup aims to investigate the cause and assess the impact of the hemorrhage. It may include an NFS, blood group and rhesus±β-HCG, hemostasis evaluation, determination of hemostasis factors, and a pelvic ultrasound. Whatever the cause of menometrorrhagia, the therapeutic options are the same and are oriented by the severity of bleeding. The treatment is mainly medical and hormonal. The surgical option should be a choice of last resort. We report a case of a 13-year-old girl admitted in hemorrhagic shock due to abundant metrorrhagia. Her laboratory tests showed an isolated deficiency of factor V with a 2 % rate. Congenital factor V deficiency is a rare autosomal recessive coagulation disorder. It can be diagnosed at any age when a bleeding disorder of varying severity is observed. The diagnosis is based on the hemostasis evaluation with quantitative determination of factor V. Because no FV-specific concentrate is available, fresh frozen plasma remains the mainstay of treatment. Antifibrinolytics can also be beneficial, and platelet transfusions have been successfully used, associated with hormone therapy. These patients may best be managed in cooperation with both a gynecologist and a hematologist. [Copyright &y& Elsevier]

It is well established that cancer increases the risk of venous thrombosis. Conversely, the mechanisms involved in haemostasis play a major role in the tumour development, facilitating tumour proliferation and altering the microenvironment, with major consequences in terms of the metastatic process. It is therefore mandatory to take the measure of this double bond between cancer and haemostasis. The clinicianwill be aware that venous thromboembolism is difficult to diagnose in cancer patients. At all stages of care, preventive and curativemeasures will be implemented, based on current recommendations and, if applicable, the standards which have been developed. With the French Group Thrombosis and Cancer (GFTC), a dynamics has been boosted in order to implement 'RCP-thrombose'. [ABSTRACT FROM AUTHOR]

The pathogenesis of the prothrombotic state of cancer patients ismostly due to the ability of cancer cells to activate the coagulation system. There are several complex and not fully understood interactions between the malignant cell and the clotting system. Tumour cells possess the capacity to interact with the haemostatic system in multiple ways. The principal mechanisms include the expression of haemostatic proteins by tumour cells, the production of inflammatory cytokines and the direct adhesion of tumour cells to platelets, endothelial cells and monocytes. This paper summarizes the prothrombotic mechanisms of tumour cells and their role in both coagulation and tumour growth and metastasis. [ABSTRACT FROM AUTHOR]

After having reviewed the different techniques of local haemostasis in oral surgery, discussed the numerous haemostatic agents on the market place and described the therapeutic attitude to observe in presence of problems of haemostasis, we illustrate the management of haemostatic troubles followed at the Division of Stomatology and Oral Surgery for over thirty years. In 1985 we almost completely discarded cyanoacrylate glue to use mainly the fibrin glue. Some thousands of dental extractions in patients with a disorder of the haemostasis were performed using the fibrin glue. A retrospective study conducted over a period of 11 years (1998-2008) has permitted the analysis of 1142 dental extractions and to confirm the constant effectiveness of this technique for local haemostasis. [ABSTRACT FROM AUTHOR]

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Copyright of Revue Francophone des Laboratoires is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Revue de Stomatologie & de Chirurgie Maxillo-Faciale is the property of Masson SPA and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Résumé: Au cours du syndrome d’activation macrophagique ou hémophagocytose lympho-histiocytaire, qu’il soit un déficit immunitaire primitif ou une maladie acquise, une stimulation anarchique et non contrôlée du système immunitaire aboutit à une infiltration et une destruction de multiples organes par des cellules cytotoxiques et des macrophages avec hémophagocytose, et une hyper-inflammation systémique. Il se traduit cliniquement par une fièvre, une organomégalie, un amaigrissement, et biologiquement par une bi/pancytopénie, une cytolyse/cholestase, une hyperferritinémie, et des troubles de l’hémostase. La mise en évidence histologique du macrophage avec hémophagocytose reste le gold standard pour beaucoup, alors qu’elle est souvent absente au tout début, ce qui peut compliquer le diagnostic. Les formes héréditaires se déclarent généralement dans la petite enfance, et sont fatales en l’absence de traitement spécifique. Chez l’adulte, l’évolution clinique va de l’hémophagocytose lympho-histiocytaire peu sévère résolutive avec le traitement de l’étiologie en cause, à la défaillance multiviscérale rapidement mortelle. De nombreuses questions se posent relatives au diagnostic et au traitement chez l’adulte qui ne font pas l’objet d’un consensus. Nous allons dans cette mise au point tenter de répondre à ces questions. [Copyright &y& Elsevier]