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Vitamin K antagonists (VKA) and direct oral anticoagulants (DOACs) are now in competition. The companies are trying to replace VKA by DOACs, totally or at least greatly VKA should VKA disappear in favor of DOACs? There are still many questions about DOACs. The purpose of this article is to make a well-considered decision in this area. The aim is not to denigrate one or the other but to share things between these two families of anticoagulants. Physicians using these drugs must have a full knowledge about compared efficacy and safety. We feel necessary to increase distance between effective results of the clinical trials and industrial communication around DOACs.

Until 1990, congenital hemorrhagic disorders were treated by plasma-derived concentrates. The first recombinant drug, recombinant factor VIII was available after this date and few years later recombinant factor IX could also be proposed to patients. The evolution of market share in France was different between these two drugs: while recombinant factor VIII took a large place in hemophilia A treatment (85%), plasma-derived factor IX represent 50% of the French market. In the next years, the arrival of long-acting antihemophilic factors may lead to the dramatically reduce the amount of plasma-derived antihemophilic factors used to treat hemophilia. For rare bleeding coagulation disorders, plasma-derived concentrates are still widely used, while they are the only concentrates available in most diseases. This situation is unlikely to evolve significantly in the next years.

Resume But Realiser un etat des lieux de la prise en charge des femmes conductrices d’hemophilie dans un CHRU francais et evaluer les differents problemes rencontres chez ces patientes. Patientes et methodes Etude retrospective concernant les conductrices d’hemophilie ayant consulte au CHRU de Montpellier entre 1995 et 2011. Le recueil des donnees a ete effectue a partir des dossiers medicaux et d’un questionnaire envoye aux conductrices. Les informations recueillies concernaient les caracteristiques biologiques, l’histoire hemorragique et la prise en charge des grossesses. Resultats Soixante-quatre conductrices d’hemophilie A ou B ont ete incluses. Leur taux de FVIII ou FIX median est de 52 % (15–137 %). Trente et un pour cent des conductrices ont des regles d’une duree superieure a 7 jours. Cent quarante-deux grossesses ont ete debutees par 54 conductrices qui ont donne naissance a 101 enfants, dont 26 garcons hemophiles. Soixante-deux diagnostics prenatals ont ete realises, 15 ont conduit a une interruption medicale de grossesse en raison d’un fœtus de sexe masculin hemophile. Soixante-seize pour cent des accouchements se sont deroules par voie basse et 49 % ont eu lieu dans une maternite de niveau III. L’accouchement a ete complique par une hemorragie du post-partum primaire dans 10,8 % des cas et secondaire dans 8,5 % des cas. Conclusion Le risque hemorragique chez les conductrices est associe a leur taux de facteur antihemophilique. Pour ameliorer la prise en charge de ces patientes, un dossier pluridisciplinaire et standardise, avec un questionnaire specifique pour evaluer les saignements pourrait etre envisage. Un registre regional repertoriant toutes les conductrices, quel que soit leur taux de facteur, serait egalement utile.

Venous thromboembolism disease (VTE) is rare in children (5.3 of 10,000 hospitalized children). However, morbidity and mortality are high, especially when the child is already suffering from severe sepsis. We report an analytical study of 24 cases of deep venous thrombosis occurring in children during infection, recorded at the Montpellier University Hospital between 1999 and 2009. Many parameters were studied in each population (age, sex, familial and personal history of thrombosis, history of thrombophilia, the presence of a venous catheter, a causative organism, time to onset of thrombus, topography of lesions, acquired abnormalities of hemostasis, and thrombosis prophylaxis). The children were aged from 1 day of life to 16 years. Thromboses occurred in two clinical contexts: "contact" thrombosis (which appeared near the infection) and disseminated thrombosis. This is an early complication because in most of the cases, it appeared in the first 10 days of sepsis. Infection and coagulation appear to be closely related and the states of latent or decompensated disseminated intravascular coagulation are common. Nevertheless, it is not possible to predict the occurence of a thrombotic event. The presence of risk factors (venous catheters, acquired thrombophilia, or constitutional thrombophilia) may increase the thrombogenic potential of the infection. VTE should always be suspected and sought in case of an unfavorable clinical course, and routine prophylaxis of thrombosis during sepsis should be discussed.

Summary. Background: Inherited factor (F)VII deficiency is the commonest of the rare bleeding disorders, with a wide set of hemorrhagic features. Other than for the severe clinical forms (for which treatment guidelines are well defined), consistent recommendations regarding perioperative replacement management do not exist for mild and asymptomatic FVII-deficient patients. Objectives: The present study aimed to evaluate the influence of bleeding history, FVII procoagulant activity levels (FVII:C) and the type of surgical procedure on the management of inherited FVII-deficient patients before surgery. Patients: One hundred and fifty-seven surgical procedures, performed without replacement therapy, in 83 unrelated FVII-deficient patients (median FVII:C = 5%, range 0.6%–35%) were analyzed. Results: The overall bleeding rate was 15.3%. We found a significant relationship between previous deep traumatic hematomas and bleeding at surgery, although relationships with previous common epistaxis, easy bruising and menorrhagia were not significant. The receiver-operating characteristic (ROC) curve analysis performed on the first 83 procedures allowed us to define a cut-off value of 7% with a sensitivity of 87% (negative predictive value: 94%). To enhance the sensitivity, and to take into account the potential variation resulting from non-standardized FVII:C measurements, we would suggest applying a threshold of 10%. Conclusion: We have proposed recommendations for the perioperative management of FVII-deficient patients based on FVII:C levels, a thorough bleeding history and the type of surgery involved. By applying these recommendations, minor procedures that risk only external or controlled hemorrhage can be performed in asymptomatic or mildly affected adults, even those with FVII:C levels below 10%.

Resume Objectifs Rapporter les cas pediatriques de syndromes d’activation macrophagique secondaires a une infection par le virus EBV observes entre janvier 1999 et decembre 2007, comparer leurs caracteristiques aux donnees de la litterature, et en degager une strategie pragmatique de prise en charge. Patients et methodes Pour chaque patient etaient notes l’âge au diagnostic, la presence d’une histoire familiale evocatrice, l’analyse des criteres diagnostiques de Henter revises en 2004, les resultats des serologies et/ou PCR EBV, les resultats des etudes genetiques realisees, le traitement et l’evolution a court et long terme. Resultats Quatre patients âges de 11 mois a sept ans ont ete hospitalises pour un tableau de mononucleose infectieuse severe avec fievre prolongee, hepato et/ou splenomegalie et stigmates biologiques d’activation macrophagique. Tous ont ete initialement traites par corticotherapie. L’evolution a ete severe pour les deux plus jeunes, avec deces dans un tableau d’insuffisance hepatocellulaire aigue dans un cas, et atteinte neurologique severe dans le deuxieme. Les deux plus âges ont bien repondu a la corticotherapie seule et sont gueris. Ils n’ont pas presente de rechute a distance. Conclusion Le syndrome d’activation macrophagique represente la complication la plus severe de la mononucleose infectieuse. Une anomalie primitive de la reponse cytotoxique doit etre de principe recherchee, en particulier chez l’enfant de moins de deux ans. Le traitement n’est pas consensuel, mais plusieurs etudes s’accordent a montrer l’interet d’un traitement immunosuppresseur contenant de l’etoposide.

Aspirin, a 110-year-old molecule, is a cornerstone in the treatment of atherothrombotic patients. The concept of aspirin "resistance" emerged approximately 15 years ago and is of growing interest. Aspirin resistance, defined as a lack of inhibition of cyclo-oxygenase-1 (COX-1), is a rare phenomenon and its clinical relevance can hardly be studied. On the contrary, residual platelet hyperactivity is more common and affects 20 to 30% of aspirin-treated patients. This latter phenomenon corresponds to sustained platelet reactivity despite a proper inhibition of COX-1 by aspirin. Several meta-analyses suggest that residual platelet hyperactivity could be a risk factor for the recurrence of ischemic events in aspirin-treated patients. Causes of biological non-responsiveness to aspirin are discussed, including the role of compliance, drug-drug interactions, genetic polymorphisms and diabetes mellitus. Ongoing studies are designed to find out the mechanisms of residual platelet hyperactivity, determine its potential clinical relevance and delineate the more appropriate assays in order to identify patients who may benefit of a tailored antiplatelet therapy.

The aim of preoperative autologous blood donation (PABD) is to reduce both the risk of transfusion transmitted disease and the need of blood from donors. One advantage of PABD is to prevent transfusion-transmitted disease namely viral infections such as HIV or hepatitis virus or emerging virus. Actually, the very low residual risk of allogeneic transfusion does not argue for PABD. On the other hand, the risk of bacterial contamination must be taken in account for both autologous and homologous transfusion (HT). A meta-analysis showed that ABD reduces the exposure to HT (OR: O.17). Clinical studies evidenced that patients who predonated autologous blood were more likely to receive any blood transfusions (autologous and/or allogeneic) than those who did not (OR: 3.31). More, the reduction of exposure to allogeneic transfusion may be questioned in view of prescription bias. Additionally, PABD is poorly cost-effective. It leads to significant blood wastage while in most studies about half of the units are discarded. In conclusion PABD is a therapy that has not been sufficiently evaluated. The interest of this therapy remains to be demonstrated.

The aim of preoperative autologous blood donation (ABD) was to reduce both the risk of transfusion transmitted disease and the need of blood from donors. Since ABD has been developed, the conditions of surgery and the criteria of choice have been modified thus leading to actualise the evaluation of this therapy. The first theoretical advantage of ABD is prevention of transfusion-transmitted disease namely viral infections such as HIV or hepatitis virus or emerging virus. Actually, the very low residual risk that remains from allogeneic transfusion after appropriate selection of donors, leukoreduction and nuclear acid testing does not argue for ABD. On the other hand, the risk of bacterial contamination must be taken in account for both ABD and homologous transfusion. A meta-analysis showed that ABD reduces the exposure to homologous transfusion (OR: 0.17). Clinical studies showed that patients who predonated autologous blood were more likely to receive any blood transfusions (autologous and/or allogeneic) than those who did not (OR: 3.31). More, the reduction of exposure to allogeneic transfusion may be questioned in view of prescription bias. Additionally, ABD is poorly cost-effective. It leads to significant blood wastage as in most of the studies about half of the units are discarded. In conclusion the interest of ABD has not been sufficiently evaluated. The interest of this therapy remains to be demonstrated.

Epidemiological studies suggest that estrogens may have opposite effects on vessels: estrogens used for contraception are known to increase both arterial and venous risk, while hormone replacement therapy could reduce the risk of cardiovascular disease. In both situations, estrogens are associated with progestogens. Progestogens are rarely used alone, thus the effect of progestogens on haemostasis or vessel wall is unclear. Data can be obtained from studies using progestogens alone or from studies comparing unopposed estrogens to combined estrogen-progestogen therapy. Progestogens alone have few effect on the haemostatic system. In combined therapy used for contraception, progestogens modify the effects of estrogens on haemostasis and endothelium: the overall effect, including modifications of coagulation factors and inhibitors could a prothrombogen trend, mainly for third generation progestogens. Unopposed estrogens are also rarely used for post menopausal hormone replacement therapy (HRT). Experimental studies have shown that progestogens are able to inhibit the beneficial effect of estrogens. Two mechanisms have been suggested: first, progestogens may reduce the endothelium-dependent vasodilatator action of estrogens. Another explanation concerns the neointimal proliferation leading to atherosclerosis: Estradiol are known to reduce this proliferation. Progestogens could reduce the protective effect of estrogens. These pharmacological effect of progestogens must be taken in account to interpret the negative results of HERS study that failed to demonstrate a cardiovascular benefit of estrogens plus progestin therapy in postmenopausal women.

Resume Le kit reticONE est un nouveau reactif propose par la societe Coulter pour la numeration des reticulocytes. Notre etude a pour but d'evaluer ce reactif sur le sang de 157 patients qui parvenaient au laboratoire central d'hematologie pendant 4 jours, par rapport a la technique cytometrique au thiazole orange et a la technique microscopique au bleu de cresyl brillant. Les resultats du kit reticONE nous paraissent satisfaisants, donnant une bonne correlation avec les methodes dites de reference et une elimination de l'interference due au marquage eventuel de l'ADN. Une evaluation plus approfondie sur un nombre plus important et plus varie de patients serait souhaitable.

Unite de medecine vasculaire, CHU de Grenoble, BP 217, 38043 Grenoble cedex 09, France UJF-Grenoble 1/CNRS TIMC-IMAG UMR 5525/Themas, 38041 Grenoble, France c Pole anesthesie-reanimation, CHU de Grenoble, BP 217, 38043 Grenoble cedex 09, France d Service d’anesthesie-reanimation, Hotel-Dieu, AP–HP, 1, place du Parvis-Notre-Dame, 75181 Paris cedex 04, France e Pole d’hematologie transfusion, centre de biologie pathologie, boulevard du Professeur-Jules-Leclercq, 59037 Lille cedex, France f Laboratoire d’hemostase, 2 bis, boulevard Tonnelle, 37032 Tours cedex, France g Laboratoire d’hemostase-thrombose, CHUM hopital Notre-Dame, 1560 Sherbrooke Est, H2L 4M1, Montreal, Canada h Laboratoire d’hemostase speciale, hopital cantonal universitaire, 4, rue Gabrielle-Perret-Gentil, 1211 Geneve 14, Suisse i Service de cardiologie, hopital St-Antoine, 184, rue du Faubourg-Saint-Antoine, 75571 Paris cedex 12, France Department of anesthesiology and critical care, hopital universitaire, Valencia, Espagne Departement d’anesthesie-reanimation, hopital Cochin, AP–HP, 27, rue du Faubourg-Saint-Jacques, 75014 Paris, France l Laboratoire central d’hematologie, hopital Saint-Eloi, CHU de Montpellier, 80, avenue Augustin-Fliche, 34295 Montpellier cedex 5, France CRTH et centre des coagulopathies, hopital du Bocage, BP 77 908, 21079 Dijon cedex, France n Laboratoire d’hematologie, groupe hospitalier Hotel-Dieu Cochin, 1, place du Parvis-Notre-Dame, 75181 Paris cedex 04, France Groupe de recherche sur la thrombose, unite de recherche clinique, innovation et pharmacologie, hopital Nord, 120, avenue Albert-Raimond, 42055 Saint-Etienne cedex 2, France p Laboratoire d’hematologie, hopital Rangueil, CHU de Toulouse, 1, avenue du Pr-Jean-Poulhess, TSA 50032, 31059 Toulouse cedex, France

BackgroundResidual platelet reactivity (RPR) has been shown to be related to adverse cardiovascular events. However, assessment of residual platelet reactivity was often evaluated in heterogeneous populations including both patients with stable disease and acute coronary syndrome.ObjectivesWe aim to delineate determinants of RPR in a cohort of stable cardiovascular patients.MethodsWe included 750 stable cardiovascular patients treated for at least one month with aspirin (n=213), clopidogrel (n=107) or both (n=425). We evaluated RPR using collagen platelet aggregation (CPA), collagen being a stimulus not directly involved in the specific pathways of aspirin and clopidogrel.ResultsMean age was 65±12 years, 76% were male; the mean duration of the CV disease was 1.6 years. CPA ranged from 6% to 96% in our population. CPA was of 41+/-16, 61+/-14 and 28+/-15% in aspirin, clopidogrel and dual treatment groups, respectively (P

Objet hors etiologies habituelles des thrombopathies, preciser le role de l’exces de facteurVIII dans la genese des accidents thrombo-emboliques veineux de l’enfant. Cas clinique un adolescent âge de 14ans consulte pour une douleur dorsale rapidement compliquee de boiterie et d’œdeme du membre inferieur gauche. Le scanner abdominal visualise une thrombose de la veine cave inferieure, des deux veines iliaques communes, de la veine femorale superficielle et profonde gauche. Sous heparinotherapie continue et traitement antalgique majeur l’evolution est favorable. Le scanner corps total de controle outre la stabilite des lesions, precise l’existence de deux embolies pulmonaires (lobe inferieur droit et pyramide gauche) cliniquement asymptomatiques. Le bilan de coagulation complet infirme les causes habituelles de thrombopathie mais precise un exces de facteur VIII > 200 % a deux reprises. L’enquete familiale est evocatrice d’une thrombopathie familiale puisque la mere et la sœur qui presentent des antecedents de phlebite du post partum sont porteuses du meme exces de facteur VIII. Conclusion si l’exces de facteur VIII est relativement frequent dans la population generale (11 %) il doit etre considere comme un facteur predisposant aux complications veineuses thrombogenes y compris chez l’enfant, a fortiori dans un contexte de thrombose intra-familiale. S’il est admis qu’il agit comme cofacteur d’une predisposition aux thromboses veineuse la mise en evidence d’un exces de facteur VIII impose un traitement anti-coagulant a long terme.