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L’hématome intracrânien spontané a un pronostic clinique sévère. Le devenir des patients dépend de l’efficacité de la prise en charge initiale. L’importance du saignement, le volume de l’hématome et son évolution sont les facteurs principaux qui contrôlent mortalité et morbidité. Les traitements anticoagulants oraux, antivitamines K (AVK) et anticoagulants oraux directs (AOD), favorisent l’expansion de l’hématome. La correction rapide de l’hémostase permet le contrôle partiel de l’hématome. Alors que la réversion des AVK par les concentrés de complexe prothrombinique (CCP) a fait l’objet de recommandations bien diffusées, l’attitude thérapeutique reste peu codifiée avec les AOD, alliant l’utilisation de l’idarucizumab pour le dabigatran et des CCP pour les anti-Xa qui n’ont, pour l’instant, pas d’antidote.

Patient blood management (PBM) is the timely application of evidence-informed medical and surgical concepts designed to maintain haemoglobin concentration, optimise haemostasis and minimise blood loss in an effort to improve patient outcomes. The aim of this consensus statement is to provide recommendations on the management of anaemia and haematinic deficiencies in pregnancy and in the post-partum period as part of PBM in obstetrics. A multidisciplinary panel of physicians with expertise in obstetrics, anaesthesia, haematology, policymaking and epidemiology was convened by the Network for the Advancement of Patient Blood Management, Haemostasis and Thrombosis (NATA) in collaboration with the International Federation of Gynaecology and Obstetrics (FIGO) and the European Board and College of Obstetrics and Gynaecology (EBCOG). Members of the task force assessed the quantity, quality and consistency of the published evidence and formulated recommendations using the system developed by the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) working group. The recommendations in this consensus statement are intended for use by clinical practitioners managing the perinatal care of women in all settings and by policymakers in charge of decision making for the update of clinical practice in health-care establishments. They need to be tailored for application in individual patients or any population after consideration of the values and preferences of both health-care providers and patients, as well as equity issues; explicit assessment of harms and benefits of each recommendation; feasibility including resources, capacity and equipment; and implementability.

Click to hear Dr Baglin's perspective on the role of the laboratory in treatment with new oral anticoagulants SUMMARY: One of the key benefits of the direct oral anticoagulants (DOACs) is that they do not require routine laboratory monitoring. Nevertheless, assessment of DOAC exposure and anticoagulant effects may become useful in various clinical scenarios. The five approved DOACs (apixaban, betrixaban, dabigatran etexilate, edoxaban and rivaroxaban) have different characteristics impacting assay selection and the interpretation of results. This article provides an updated overview on (i) which test to use (and their advantages and limitations), (ii) when to assay DOAC levels, (iii) how to interpret the results relating to bleeding risk, emergency situations and perioperative management, and (iv) what is the impact of DOACs on routine and specialized coagulation assays. Assays for anti-Xa or anti-IIa activity are the preferred methods when quantitative information is useful, although the situations in which to test for DOAC levels are still debated. Different reagent sensitivities and variabilities in laboratory calibrations impact assay results. International calibration standards for all specific tests for each DOAC are needed to reduce the inter-laboratory variability and allow inter-study comparisons. The impact of the DOACs on hemostasis testing may cause false-positive or false-negative results; however, these can be minimized by using specific assays and collecting blood samples at trough concentrations. Finally, prospective clinical trials are needed to validate the safety and efficacy of proposed laboratory thresholds in relation to clinical decisions. We offer recommendations on the tests to use for measuring DOACs and practical guidance on laboratory testing to help patient management and avoid diagnostic errors. ispartof: Journal of Thrombosis and Haemostasis vol:16 issue:2 pages:209-219 ispartof: location:England status: published

I farmaci derivati dal plasma (FDP) sono delle proteine terapeutiche indicate come trattamento sostitutivo di deficit quantitativi o qualitativi, costituzionali o acquisiti in proteine essenziali. Questi prodotti sono preparati industrialmente a partire dal plasma umano secondo un procedimento di alta tecnologia, il frazionamento plasmatico, garantendo la loro efficacia e una sicurezza massimale nei confronti del rischio infettivo. Lo status di «farmaco» impone il rispetto di un protocollo rigido e regolamentato. Noi trattiamo i FDP usati a scopo antiemorragico e antitrombotico, nel quadro di patologie spesso gravi, a volte rare, in situazioni croniche o in urgenza, in situazioni che minacciano la prognosi vitale. La loro frequenza di utilizzo e molto variabile. I fattori VIII, IX e di von Willebrand sono i piu prescritti, in profilassi o nel trattamento delle complicanze emorragiche. Dal momento che i deficit costituzionali in fattori XI, XIII, antitrombina e proteina C sono molto rari, l’utilizzo dei concentrati di fattori corrispondenti e aneddotico. Viceversa, i concentrati di complesso protrombinico non attivato e attivato e i concentrati di fibrinogeno occupano un ruolo crescente nell’arsenale terapeutico come agenti emostatici nella gestione delle emorragie massive associate a deficit acquisiti.

Los medicamentos derivados del plasma (MDP) son proteinas terapeuticas que se prescriben como tratamiento sustitutivo de deficits cuantitativos o cualitativos, constitucionales o adquiridos, de proteinas esenciales. Estos productos se preparan industrialmente a partir del plasma humano con un procedimiento de alta tecnologia, denominado fraccionamiento plasmatico, que garantiza su eficacia y una seguridad maxima respecto al riesgo infeccioso. El estatus de «medicamento» supone ajustarse a un protocolo estricto y reglamentado. Aqui se han de considerar los MDP que se usan con objetivo antihemorragico y antitrombotico en el contexto de patologias a menudo graves, a veces infrecuentes, en situacion cronica o de urgencia, y en casos que amenazan el pronostico vital. La frecuencia con la que se usan es muy variable. Los factores VIII, IX y de Von Willebrand son los que mas se prescriben, ya sea como profilaxis o tratamiento de las complicaciones hemorragicas. Dado que los deficits constitucionales de factores XI, XIII, antitrombina y proteina C son muy infrecuentes, el uso de los concentrados de factores correspondientes es excepcional. En cambio, los concentrados de complejo protrombinico no activado y activado, asi como los concentrados de fibrinogeno, ocupan un lugar creciente en el arsenal terapeutico como agentes hemostaticos en el manejo de las hemorragias masivas vinculadas a deficits adquiridos.

Resume L’objectif a ete d’evaluer, a partir de donnees de la litterature, le risque d’hemorragies fatales qu’ajouterait un eventuel traitement anticoagulant curatif des thromboses veineuses asymptomatiques depistees par un echo-doppler systematique apres protheses totales de hanche/genou, et de fractures de hanche. Materiel et methodes L’incidence des evenements thromboemboliques et hemorragiques avec la prophylaxie recommandee et celle des hemorragies majeures iatrogenes liees au traitement anticoagulant curatif, ont ete extraites d’essais cliniques randomises, d’analyses des codages de pathologies en sortie d’hospitalisation, de registres et enquetes observationnelles. L’incidence des evenements mortels a ete calculee pour l’embolie pulmonaire, les hemorragies sous prophylaxie, et les hemorragies iatrogenes sous anticoagulation curative, en multipliant le taux moyen de l’evenement symptomatique par son coefficient de mortalite. Les taux d’evenements mortels ont ete evalues pour un ensemble theorique de 10 000 protheses totales de hanche/genou, et de 10 000 fractures de hanche. Resultats Sur 10 000 patients apres protheses de hanche/genou, cinq embolies pulmonaires fatales et deux hemorragies fatales sont attendues malgre la prophylaxie recommandee. L’anticoagulation curative des thromboses asymptomatiques sous-jacentes ajouterait neuf hemorragies fatales dont huit liees au traitement des seules thromboses distales. Sur 10 000 fractures de hanche soumises a une prophylaxie prolongee, six embolies pulmonaires fatales et 23 hemorragies fatales sont attendues. L’anticoagulation curative des thromboses asymptomatiques ajouterait 16 hemorragies fatales dont 14 liees au traitement des seules thromboses distales. Conclusion L’anticoagulation curative des thromboses veineuses asymptomatiques, en particulier distales, conduirait a davantage de deces par hemorragie qu’elle ne pourrait en eviter par embolie pulmonaire, ce qui renforce la recommandation de ne pas les depister.

Direct oral anticoagulants (DOAs), inhibitors of factor IIa or Xa, are expected to replace vitamin K antagonists in most of their indications. It is likely that patients on long-term treatment with DOAs will be exposed to elective or emergency surgery or invasive procedures. Due to the present lack of experience in such conditions, we cannot make recommendations, but only propose perioperative management for optimal safety as regards the risk of bleeding and thrombosis. DOAs may increase surgical bleeding, they have no validated antagonists, they cannot be monitored by simple, standardised laboratory assays, and their pharmacokinetics vary significantly from patient to patient. Although DOAs differ in many respects, the proposals in the perioperative setting need not be specific to each. For procedures with low risk of haemorrhage, a therapeutic window of 48 h (last administration 24h before surgery, restart 24h after) is proposed. For procedures with medium or high haemorrhagic risk, we suggest stopping DOAs 5 days before surgery to ensure complete elimination of the drug in all patients. The treatment should be resumed only when the risk of bleeding has been controlled. In patients with a high risk of thrombosis (e.g. those in atrial fibrillation with an antecedent of stroke), bridging with heparin (low molecular weight, or unfractionated if the former is contraindicated) is proposed. In emergency, the procedure should be postponed for as long as possible (minimum 1-2 half-lives) and non-specific anti-haemorrhagic agents, such as recombinant human activated factor VIIa, or prothrombin concentrates, should not be given for prophylactic reversal, due to their uncertain benefit-risk.

The overall thromboembolic risk is the resultant of patient-related risk and surgical risk. The surgical risk is decreasing, especially with the introduction of new procedures (fast-track surgery). The value of prophylaxis has been firmly established. Mechanical prophylaxis is to be used as first-line prophylaxis when there is a risk of bleeding. Combining this with drugs increases the antithrombotic efficacy. However, the effectiveness of prophylaxis on pulmonary embolism and mortality has not been demonstrated. Renal function needs to be evaluated when low molecular weight heparins, fondaparinux, rivaroxaban or dabigatran are prescribed. An age of over 75 years and low body weight (

La trombosis venosa profunda es el resultado de un fenomeno fisiologico que se desarrolla en un lugar no deseado de la red venosa. Se produce por razones que pocas veces estan relacionadas con trastornos de la coagulacion (trombofilia), sino sobre todo con la estasis venosa y con lesiones endoteliales. Estos tres elementos constituyen la clasica triada de Virchow. Es probable que el factor tisular sea un mediador determinante de la enfermedad tromboembolica, cuyas consecuencias locales pueden producir molestias funcionales en la pierna y ser potencialmente catastroficas si da lugar a una embolia pulmonar. La cirugia ortopedica y traumatologica es causa destacada de enfermedad venosa tromboembolica, sobre todo las protesis totales de cadera y de rodilla, asi como las fracturas del extremo superior del femur, que aparecen en una poblacion a menudo envejecida, con una movilidad reducida, con sobrepeso y con factores frecuentes de comorbilidad. La profilaxis farmacologica ha experimentado progresos considerables en las ultimas decadas, hasta el punto de que la embolia pulmonar mortal se ha convertido en excepcional, por fortuna. En cambio, no esta desprovista de riesgos y, en la actualidad, el carne de identidad de un antitrombotico debe incluir un estudio preciso de dos aspectos: el beneficio profilactico y el riesgo hemorragico. Los estudios se realizan en poblaciones escogidas y se basan en las pruebas complementarias, que son mas sensibles que los fenomenos clinicos gracias a la frecuente positividad. Deben completarse mediante cohortes de pacientes de la «vida real». La flebografia ya no se emplea mas que en los estudios. La eco-Doppler es la exploracion de rutina en la practica clinica. La farmacopea aumenta con regularidad gracias a nuevas moleculas, procedentes en la mayoria de los casos de la fragmentacion de la heparina, que bloquean la formacion de trombina mediante el factor X activado o directamente la propia trombina. La eficacia de los medicamentos ha creado un autentico apasionamiento por su utilizacion, y la tendencia actual deberia ser mas selectiva para adaptar a cada paciente concreto la molecula, su posologia, la hora de la primera inyeccion, asi como su ritmo de prescripcion, pasando de la epoca del tratamiento «listo para administrar» a la del tratamiento «sobre medida».

Resume Le schema moderne de l’hemostase fait jouer un role de starter au facteur tissulaire et donne de fait une grande importance au facteur VII. Il rehabilite le role essentiel des plaquettes et identifie la thrombine comme facteur central de la coagulation. Des elements complementaires doivent a present etre pris en compte pour avoir une vision globale de l’hemostase et ne pas aggraver un trouble deja existant. Ainsi, une chute du nombre de globules rouges altere l’hemostase primaire (adhesion et agregation plaquettaire) et reduit la generation de thrombine. L’hypothermie atteint le fonctionnement plaquettaire et la cinetique des facteurs de la coagulation. Les roles du choc et de l’hypocalcemie sont moins bien definis, mais doivent toujours etre evoques. Enfin, la dilution en rapport avec des solutes de remplissage peut encore aggraver une situation critique, surtout s’ils exercent un effet propre sur l’hemostase comme les amidons de haut poids.

Summary. Background: Recent changes in the management of hip fracture surgery patients may have modified the epidemiology of postoperative complications. Objectives: We performed an observational study of a cohort of patients undergoing hip fracture surgery to update the epidemiological data on this population. The primary study outcome was the incidence of confirmed symptomatic venous thromboembolism (VTE) [defined as deep vein thrombosis, pulmonary embolism (PE), or both] at 3 months. Overall mortality at 1, 3 and 6 months was also evaluated. Patients/methods: Consecutive patients aged at least 18 years hospitalized in French public or private hospitals (531 centers) undergoing hip fracture surgery were recruited prospectively during 2 months in 2002 and a follow-up at 6 months. Predictive factors for VTE at 3 months and for death at 6 months were also analyzed. Results: Data from 6860 (97.3%) of the 7019 recruited patients were included in the analysis. The median age was 82 years. Low molecular weight heparins were administered perioperatively in 97.6% of patients; 69.5% received this treatment for at least 4 weeks. The actuarial rate of confirmed symptomatic VTE at 3 months was 1.34% (85 events, 95% CI: 1.04–1.64). There were 16 PEs (actuarial rate: 0.25%), three of which were fatal. Overall, 1006 (14.7%) patients were dead at 6 months. Cardiovascular disease was the most frequent cause of death (270 patients; 26.8%). Conclusions: The current rate of postoperative VTE is low, but overall mortality remains high. Indeed, hip fracture patients belong to a vulnerable group of old people with comorbid diseases and a high risk of postoperative morbidity and mortality. An interdisciplinary approach could be the challenge to improve short and long-term outcome.

Several haemostasis point-of-care (POC) monitors are now available in the operating theatre. Two of these are widely used; the Coaguchek® and the thromboelastograph (TEG), but they have been developed in very different ways. Bedside-activated partial thromboplastin time and prothrombin time performed with the Coaguchek monitor seem to be reliable and have been used to build algorithms for transfusion decision making. They have been developed in close collaboration with haemostasis groups and therefore gain a benefit from these links. Conversely, TEG provides very important information except it has never been validated. The number of collaborative studies with biologists has to increase in order to implement the use of TEG in the routine practice.

Assess the efficacy and safety of tranexamic acid administration for the prevention and/or the treatment of postpartum haemorrhage.Systematic review with meta-analysis.Systematic review of the literature with the aim of identifying prospective, randomised, controlled trials that assessed the effect of tranexamic acid on peripartum blood loss and transfusion requirement in three clinical contexts: (i) prevention of post-partum haemorrhage in case of elective caesarean section, (ii) prevention of post-partum haemorrhage in case of vaginal delivery, (iii) treatment of post-partum haemorrhage.Prophylactic administration of tranexamic acid reduced blood loss (mean difference for intraoperative blood loss: -177.9mL, IC 95%: -189.51 to -166.35, total blood loss: -183.94, IC 95%: -198.29 to -169.60), and the incidence of severe post-partum haemorrhage (OR: 0.49, IC 95%: 0.33 to 0.74). None of the published trials assessed the effect of tranexamic acid on blood products administration or transfusion requirement. Only one study assessed and reported the efficacy of tranexamic acid when administered as a treatment for postpartum haemorrhage. A significant reduction in blood loss was reported within 30 minutes after randomisation (P=0.03) and confirmed after 6 hours (median: 170mL (58-323) vs 221mL (110-543), P=0.04). None of the included studies adequately studied the incidence of side effects after tranexamic acid administration.Although tranexamic acid administration seemed to significantly reduce blood loss and the incidence of severe post-partum haemorrhage, further prospective trials are needed to confirm the efficacy and safety of tranexamic administration in the treatment of postpartum haemorrhage. Those studies should assess the pharmacokinetic profile and the safety of this drug in pregnant women.

L’epidemiologie et les modes de prevention de la maladie thromboembolique veineuse (MTEV) en reanimation sont encore assez imprecis. Si l’existence du risque thromboembolique en tant que tel n’est pas discutee, sa quantification pose encore des problemes qui retentissent sur les differents modes de prophylaxie utilises. La litterature est pauvre. Les travaux sont le plus souvent observationnels et non randomises, et les comparaisons retrospectives, a l’exception de quelques etudes recentes. En l’absence de travaux specifiques, les demarches preventives adoptees sont souvent calquees sur celles adoptees en medecine, en pediatrie ou en chirurgie [1]. La complexite du patient de reanimation rend peut-etre compte de cette absence de donnees. Les modes de prophylaxie mecanique et medicamenteuse sont decrits ici, en reanimation chirurgicale et medicale comme en pediatrie.

The current issues debate will bring together experts around the themes of self-sufficiency (in its national and European aspects) and of needs in cellular blood products. The point of view of the manufacturer and prescribers of blood products will be confronted.

The management of massive bleeding has improved, thanks to high-quality blood components and new transfusion strategies. However, it remains controversial and, despite a huge body of literature, randomised control trials are still lacking. However, the therapeutic approach has also evolved, requiring earlier and more active management. If a 'no delay' management is well recognized, its modes are still discussed. Immediate delivery of blood products with ratios close to 1:1:1 for RBC units/fresh frozen plasma/platelet concentrates, through massive transfusion protocol using blood packs, has been advocated, but yet this approach is not evidence-based. Secondly, a targeted strategy to provide fibrinogen concentrates is under evaluation. Tranexamic acid is effective in trauma patients. Recombinant factor VIIa should only be used on a compassionate basis.

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 30ng/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, 30-50U/kg, or non-activated 4-factors prothrombin concentrates 50U/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.

Rare inherited bleeding disorders include fibrinogen disorders, and deficiencies of factors II (prothrombin), V, VII, X, XI, XIII, and combined V+VIII, and combined vitamin K-dependent factors, with general population prevalence rates between 1/500,000 and 1/2,000,000. These inherited disorders, transmitted as autosomal recessive traits, are characterized by a heterogeneous clinical presentation (asymptomatic, mild, moderate or severe bleeding tendency); this variability is more important for deficiencies with factor levels ranging from 5 to 50%. Individual bleeding risk assessment before an invasive procedure or during peri-partum period remains difficult, although an essential step to decide whether a substitution with clotting factor is necessary or not. Because there is a poor correlation between factor activity levels and the severity of bleeding symptoms, factor correction before an invasive procedure should not be based on factor level only, but physicians must also take into account the patient phenotype as well as the haemorrhagic risk of the procedure.

The study objective was to evaluate the potential increase in fatal bleeding risk related to curative anticoagulation of asymptomatic deep venous thromboses diagnosed by routine ultrasound screening after total hip/knee replacement or hip fracture using data from a comprehensive literature review.Rates of venous thromboembolic and bleeding events occurring with recommended prophylaxis, and rates of iatrogenic bleeding risk induced by curative anticoagulation were extracted from randomized clinical trials, diagnosis codes at discharge, electronic databases, and observational studies. The fatal events rate was calculated for pulmonary embolism, major bleeding with prophylaxis, and iatrogenic bleeding from curative anticoagulation by multiplying the mean rate by its case-fatality rate. Fatal event rates were evaluated for 10,000 total hip or knee replacements and for 10,000 hip fractures.For 10,000 patients undergoing total hip or knee replacement, five fatal pulmonary embolisms and two fatal bleedings are expected, despite recommended extension of thromboprophylaxis. Curative anticoagulation of asymptomatic venous thrombosis would add nine fatal bleedings, 8/9 related to distal thrombosis care. For 10,000 patients undergoing hip fracture surgery, six fatal pulmonary embolisms and 23 fatal bleedings are expected. Curative anticoagulation of asymptomatic venous thrombosis would add 16 fatal bleedings, 14/16 related to distal thrombosis care.Curative anticoagulation of asymptomatic distal deep vein thromboses, leads to more fatal bleeding compared to avoidable fatal pulmonary embolism. These findings strengthen recommendations against routine ultrasound screening for asymptomatic distal deep vein thrombosis.

Even with unfractionated heparin or derivates, the reversal of pharmacologic anticoagulation is crucial in anticoagulated patients developing a life-threatening bleeding or scheduled for an emergency procedure. The antagonisation of unfractionated heparin is well codified: each milligram of protamine sulfate antagonizes 100 IU of heparin. Measurement of thrombin time reflects the anti-IIa effect of heparin and has to be monitored immediately and 1hour after the injection of protamine. The required dose of protamine sulfate depends on dosage and time of LMWH administration, although no clinical study supports these data. To date, there is no effective antidote for new anticoagulants (fondaparinux and other pentasaccharides, direct thrombin inhibitors, direct anti-Xa inhibitors). Some preliminary studies suggest the effectiveness of recombinant activated factor VII for pentasaccharides and activated or not Prothrombin Complex Concentrates and recombinant activated factor VII for oral anti-Xa and anti-IIa agents. Therefore, while the characteristics of these new anticoagulants could increase the comfort and improve the compliance, their development needs to ascertain the lack of increase in bleeding complications and the need for a safe and effective antidote.

Thromboembolic accidents are a frightening complication of plastic and aesthetic surgery. The absence of recommendations for professional practices for the prevention of such accidents justified this work. The therapeutic practices of the surgeons were analysed and the results were then compared with those of the international literature. The analysis by a group of experts made it possible to establish recommendations for professional practices.This work consisted in collecting, retrospectively, the therapeutic practices and the complications of 440 surgeons, concerning four types of interventions (abdominoplasty, mammoplasty, abdominal lift and liposuction), from 2006 to 2008, i.e., approximately 110.000 interventions.The intervention with the greatest risk is abdominoplasty with 0.9% of thromboembolic accidents; the intervention with the least risk is mammoplasty with 0.1% of accidents. The risk with the abdominal lift and liposuction of more than three zones is similar and intermediate with 06% of accidents. A protocol of prevention of thromboembolic accidents in plastic surgery is proposed.

Direct oral anticoagulants (DOAs), inhibitors of factor IIa or Xa, are expected to replace vitamin K antagonists in most of their indications. It is likely that patients on long-term treatment with DOAs will be exposed to elective or emergency surgery or invasive procedures. Due to the present lack of experience in such conditions, we cannot make recommendations, but only propose perioperative management for optimal safety as regards the risk of bleeding and thrombosis. DOAs may increase surgical bleeding, they have no validated antagonists, they cannot be monitored by simple, standardised laboratory assays, and their pharmacokinetics vary significantly from patient to patient. Although DOAs differ in many respects, the proposals in the perioperative setting need not be specific to each. For procedures with low risk of haemorrhage, a therapeutic window of 48 h (last administration 24h before surgery, restart 24h after) is proposed. For procedures with medium or high haemorrhagic risk, we suggest stopping DOAs 5 days before surgery to ensure complete elimination of the drug in all patients. The treatment should be resumed only when the risk of bleeding has been controlled. In patients with a high risk of thrombosis (e.g. those in atrial fibrillation with an antecedent of stroke), bridging with heparin (low molecular weight, or unfractionated if the former is contraindicated) is proposed. In emergency, the procedure should be postponed for as long as possible (minimum 1-2 half-lives) and non-specific anti-haemorrhagic agents, such as recombinant human activated factor VIIa, or prothrombin concentrates, should not be given for prophylactic reversal, due to their uncertain benefit-risk.

Hydroxyethyl starches (HES) could differ with regard to the origin, and the influence on the coagulation of the raw material is unknown. This study compared the effects of a new potato-derived HES with a maize-derived HES and two crystalloid solutions.Whole blood from 10 healthy individuals was diluted by 20% and 40% using either non-balanced potato-derived HES 130/0.42/6:1, non-balanced maize-derived HES 130/0.4/9:1, isotonic saline or Ringer's lactate solution. Samples were analysed by thromboelastometry ROTEM(®) : Coagulation was initiated by acid ellagic [intrinsic thromboelastometry (INTEM)] or tissue factor (extrinsic thromboelastometry) with and without cytochalasin to determine the functional component of fibrinogen [cytochalasin-d-modified thromboelastometry (FIBTEM)]. Platelet count and fibrinogen activity were measured.No effect of raw material was found as no difference was detected among the HES solutions. Whatever the solution, progressive haemodilution impaired haemostasis in a dose-dependant manner: For INTEM, the clot formation time was increased up to 308% and the maximum clot firmness (MCF) was decreased down to 49%. As dilution increased, initiation of coagulation was also impaired. Thromboelastometric alterations were more severe with HES than with crystalloids, especially regarding fibrin polymerization explorations: MCF of FIBTEM was considerably reduced from 12[10-14] to 2[2-3] mm (P0.05). Fibrinogen activity and platelet count were reduced by dilution in a dose-dependant manner and decreased similarly in all groups.Maize- and potato-derived HES have similar effects on coagulation. Both the starch preparations tested lead to more severe haemostatic defects than crystalloids, and impairment of fibrin polymerization appears to be a leading determinant of this coagulopathy.

The anticoagulant market has been very active recently with the development of new compounds including injectable anti-Xa such as fondaparinux, already available, and idraparinux, already replaced by its new biotynilateed form, and new oral drugs which can be divided into anti-IIa with dabigatran already available, and anti-Xa, such as the recently marketed rivaroxaban and apixaban still in the development stage. Others are coming forward. The competition is strong and the place for each drug remains to be determined. This review discusses these new anticoagulants in terms of efficacy and tolerance based on data in the literature. These recent reports mainly concern prophylaxis for orthopedic surgery but also consider treatment of deep venous thrombosis. The results of studies in heart patients have raised much curiosity since they will be determinant in the future use of innovating compounds, which could replace current oral anticoagulants. This will be upcoming but not yet for tomorrow.

Extensive evidence related to thromboembolism risk and its prevention are available to guide health care providers. The 8th ACCP Evidence-Based Clinical Practice Guidelines were published in June 2008. The chapter on venous thromboembolism prophylaxis is the result of the collaboration of six senior authors with expertise in thrombosis, surgery, medicine, and critical appraisal. The methodology and the philosophy of these guidelines are explained in this paper and the major recommendations dealing with perioperative thromboprophylaxis are summarized.

The overall thromboembolic risk is the resultant of patient-related risk and surgical risk. The surgical risk is decreasing, especially with the introduction of new procedures (fast-track surgery). The value of prophylaxis has been firmly established. Mechanical prophylaxis is to be used as first-line prophylaxis when there is a risk of bleeding. Combining this with drugs increases the antithrombotic efficacy. However, the effectiveness of prophylaxis on pulmonary embolism and mortality has not been demonstrated. Renal function needs to be evaluated when low molecular weight heparins, fondaparinux, rivaroxaban or dabigatran are prescribed. An age of over 75 years and low body weight (50 kg) have to be taken into account. There is a risk of spinal or epidural hematoma in patients receiving anticoagulants. Caution should be taken especially when administering the newer agents. Patients undergoing surgery that involves a moderate or high overall risk should receive prophylaxis until full mobilization. Patients who have undergone a total hip replacement, surgery for hip fracture, or major abdominal surgery should receive prophylaxis for about 5 weeks longer. The relevance of distal vein thromboses is debated. Surrogate venographic end-points should be gradually replaced by a combination of ultrasound and clinical criteria. The new antithrombotic agents will probably modify prevention in the years to come but currently there are very few long-term data for these products for which - it should be reminded - no antagonists are available.

The iatrogenicity of vitamin K antagonists is well established. Each year in France, vitamin K antagonists account for more than 17,000 hospital admissions and nearly 4000 deaths. Alternative treatment would be more than welcome. It is hard to imagine a drug that would induce more complications than a vitamin K antagonist.

Prothrombin complex concentrates are haemostatic blood products containing four vitamin K-dependent clotting factors (II, VII, IX and X). They are a useful, reliable and fast alternative to fresh frozen plasma for the reversal of the effects of oral anticoagulant treatments (vitamin K antagonists). They are sometimes used for factor II or factor X replacement in patients with congenital or acquired deficiencies. They are widely prescribed in Europe. Several retrospective and prospective studies have demonstrated their efficacy in normalizing coagulation and in helping to control life-threatening bleeding. Few side-effects, mainly thromboembolic events, have been reported. The link between these events and prothrombin complex concentrate infusion has, however, often been brought into question. The use of prothrombin complex concentrates in new promising indications such as the management of massive bleeding requires prospective studies providing a high level of evidence in a high-risk setting.

We report 13 cases of coronary stent patients, undergoing a non cardiac surgery. Despite an heterogenous perioperative management of antiplatelet agents, none of these patients developed any significant complications. Recently, several case reports of postoperative drug eluting stent thrombosis have been reported. However, the actual incidence of this dramatic event is not known. This confirms the need to perform prospective studies or registries of patients with coronary stents undergoing non cardiac surgery, in order to propose evidence-based recommendations on perioperative antiplatelet management in such patients.

The aim of this paper is to present the recommendations of the Agence Française de Sécurité Sanitaire des Produits de Santé (AFSSaPS; French Safety Agency for Health Products). A panel of experts reviewed and graded the literature on platelet transfusions; recommendations were formulated. Threshold platelet counts (PC) for transfusions in the perioperative context have not been clearly defined and should be determined by the existence of hemorrhagic risk factors. In the case of commonly practiced invasive procedures, the recommendation is to transfuse in order to achieve PC50,000 x microL-1. In the absence of platelet dysfunction, regardless of the type of surgery, the standard hemorrhagic risk threshold for surgery is 50,000 x microL-1. It has not been proven that the risk threshold is different according to the type of surgery. For neurosurgery and ophthalmologic surgery involving the posterior segment of the eye, a PC of 100,000 x microL-11 is required. For axial regional anesthesia, a PC of 50,000 x microL-11 is sufficient for spinal anesthesia; a PC of 80,000 x microL-11 has been proposed for epidurals. During massive transfusion, prophylactic platelet infusion cannot be recommended beyond a loss of two blood volumes in less than 24 h (Professional Consensus). As for the therapeutic transfusion of plasma and/or platelets, as much as possible, platelet deficit should be documented with test results (PC and fibrinogen) before transfusing. In the event of bleeding, platelet transfusion may precede plasma infusion. However, although this recommendation has been the subject of several professional consensus agreements, it is not based on any randomized studies. Threshold PC for perioperative transfusions have not been clearly defined and most recommendations are the result of a professional consensus.

This study was undertaken to quantify the use of chronic medication and herbal remedies in the presurgical population.Prospective multicenter survey.Adult patients presenting for anaesthesia were directly asked if they were currently using chronic medication or herbal remedies.Among 1057 patients (age 54+/-17 yrs, woman 54%, ASA 2 [1-4], 74%) were taking one or more chronic medication. The most commonly used treatments were, in descending order angiotensin-converting enzyme inhibitors and angiotensin-II receptor blockers (15%), beta blockers (11%) and platelet inhibitors (10%). Also, 9% were taking one or more of the following herbal remedies known to interact with the perioperative period: valeriane, ginseng, ginkgo, St John's wort, echinacea and ephedra. Women and patients aged 40-70 yr were most likely to be taking a herbal product (p0.001 and p0.01 respectively).Chronic medication and herbal remedies are common in patients presenting for anaesthesia. Because of the potential interactions between anaesthetic drugs or techniques and such medication it is important for anaesthetists to be aware of their use.

The French Society of anaesthesiology and intensive care has chosen a high level methodology to issue professional Recommendations on perioperative and obstetrical venous thromboembolism prophylaxis. In addition with a short review on mechanical and pharmacological prophylaxis, all surgical and obstetrical settings have been studied. The initiation and duration of prophylaxis have been particularly debated in close relation with the level of surgical risk. A large group of experts has been involved in this process. More than 150 other experts have participated in the reading process. Didactic tables have been added to help the prescription.