We analysed changes in coagulation during normal pregnancy with a novel point-of-care device based on thrombelastometry (ROTEM). We compared the results obtained with those of standard coagulation ...tests in 104 patients: 20 non-pregnant women (controls) and 84 women in the first (T1, n = 17), second (T2, n = 9) and third (T3, n = 58) trimesters of pregnancy. We measured the clotting time (CT), the maximum clot firmness (MCF), the early clot amplitude at 5 and 15 minutes (CA(5), CA(15)) and the clot lysis index (CLI(30)) with four tests containing specific reagents. (a) The INTEM test involving ellagic acid activated the intrinsic pathway and (b) the EXTEM test using tissue factor triggered the extrinsic pathway; (c) The FIBTEM test based on a platelet inhibitor (cytochalasin D) evaluated the contribution of fibrinogen to clot formation and (d) the APTEM test was similar to the EXTEM but was based on inhibition in vitro of fibrinolysis by aprotinin. CT and CLI(30) were not significantly modified during pregnancy whereas MCF, CA(5) and CA(15) (INTEM, EXTEM, FIBTEM) increased significantly between the second and third trimesters (e.g. median interquartile range: MCF-FIBTEM, 13 11-16 mm vs. 19 17-23 mm, respectively, in controls and T3, p < 0.001). EXTEM values were not significantly different from those measured with APTEM. There were significant correlations between the results obtained with ROTEM and those from standard coagulation tests. ROTEM analysis showed a marked increase in coagulability during normal pregnancy. ROTEM values may serve as the basis for future studies in pregnant women.
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.
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.
L’héparine non fractionnée (HNF) et surtout les héparines de bas poids moléculaire (HBPM) ou le fondaparinux sont largement utilisés dans la prophylaxie et le traitement de la phase aiguë de la ...maladie thromboembolique veineuse ou artérielle. La surveillance des traitements, nécessaire surtout pour les traitements à doses curatives, est conditionnée par les profils pharmacocinétiques des différentes molécules. Il existe une grande variabilité inter et intra-individuelle de l’activité anticoagulante de l’HNF de sorte qu’un contrôle journalier est nécessaire pour tous les patients soit par le TCA, soit par la détermination de l’activité anti-Xa. Les HBPM et le fondaparinux avec une biodisponibilité proche de 100 % ont des effets beaucoup plus prévisibles et la surveillance de l’activité anticoagulante, par mesure de l’activité anti-Xa uniquement, concerne essentiellement les patients avec insuffisance rénale ou ceux de poids extrême. Dans tous les cas, un strict respect des conditions pré-analytiques est requis pour une bonne interprétation des résultats. Enfin le contrôle des plaquettes, pour un diagnostic précoce d’une thrombopénie à l’héparine, est systématique dans tous les cas où l’on utilise l’HNF et concerne surtout les malades en situation chirurgicale quand c’est une HBPM qui est utilisée et il n’est pas nécessaire pour les malades sous fondaparinux.
Unfractionated heparin (UH) and above all low molecular weight heparin (LMWH) and fondaparinux are widely used for the prevention and treatment of the acute phase of venous or arterial thrombosis. The laboratory monitoring is based on the pharmacokinetic profiles of the different heparins. There is an important intra and inter individual variability of the anticoagulant response of UH that makes necessary a daily monitoring for all patients either by activated partial thromboplastin time or by an anti-Xa activity determination. HBPM and fondaparinux because of their heigh bioavailability have more predictable effects on hemostasis so that laboratory monitoring is essentially for patients with renal dysfunction or with low or high body weight. In any cases preanalytical parameters have to be strictly taken into account for a good interpretation of the biological results. At least platelet-count monitoring is very important for an early detection of type II heparin-induced thrombocytopenia for all patients with UH and in surgical patients treated with LMWH.
Summary
Acquired factor V inhibitor (AFVI) is an extremely rare disorder that may cause severe bleeding. To identify factors associated with bleeding risk in AFVI patients, a national, multicentre, ...retrospective study was made including all AFVI patients followed in 21 centres in France between 1988 and 2015. All patients had an isolated factor V (FV) deficiency <50% associated with inhibitor activity. Patients with constitutional FV deficiency and other causes of acquired coagulation FV deficiencies were excluded. The primary outcome was incident bleeding and factors associated with the primary outcome were identified. Thirty‐eight (74 36–100 years, 42·1% females) patients with AFVI were analysed. Bleeding was reported in 18 (47·4%) patients at diagnosis and in three (7·9%) during follow‐up (7 0·2–48.7 months). At diagnosis, FV was <10% in 31 (81·6%) patients. Bleeding at diagnosis was associated with a prolonged prothrombin time that strongly correlated with the AFVI level measured in plasma {r = 0·63, 95% confidence interval (CI) 0·36–0·80, P < 0·05}. Bleeding onset during follow‐up was associated with a slow AFVI clearance (P < 0·001). The corresponding receiver operating characteristics curve showed that AFVI clearance was predictive of bleeding onset with an AFVI clearance of seven months with a sensitivity of 100% (95% CI: 29–100) and a specificity of 86% (95% CI: 57–98, P = 0·02). Kaplan–Meier analysis showed that AFVI clearance >7 months increased the risk of bleeding by 8 (95% CI: 0·67–97, P = 0·075). Prothrombin time at diagnosis and time for clearance of FV inhibitor during follow‐up are both associated with bleeding in patients with AFVI.
Il existe au cours de la grossesse une hypercoagulabilité physiologique qui peut être majorée par des facteurs de risque génétiques et/ou acquis de thrombose. Cela augmente le risque de maladie ...thromboembolique et le risque de thrombose dans les vaisseaux du placenta et ainsi d’arrêt de grossesse. Parmi les facteurs génétiques de risque de thrombose, le facteur V Leiden et le facteur II muté sont responsables de fausses couches spontanées (FCS), tardives essentiellement. Les rares déficits en antithrombine, protéine C et protéine S sont également impliqués. Les facteurs génétiques de risque de thrombose d’origine paternelle qui pourraient affecter directement le fœtus ne semblent pas impliqués. C’est le syndrome des antiphospholipides (SAPL), à l’origine de 15 % des FCS récidivantes, qui est le plus fréquent avec des FCS qui surviennent à tous les stades de la grossesse, précocement en perturbant l’invasion trophoblastique, ou tardivement par thrombose des vaisseaux du placenta. Le traitement du SAPL chez la femme enceinte, aspirine et héparine bas poids moléculaire, est efficace. La production excessive de microparticules phospholipidiques, une diminution de l’annexine V à la surface des trophoblastes, le génotype 4G/4G du PAI-1 pourraient expliquer des arrêts de grossesse.
During pregnancy there is a hypercoagulable state that is sometimes enhanced by genetic and/or acquired thrombosis risk factors. This enhances the risk of thromboembolic events and the risk of thrombosis in the vessels of the placenta and thus pregnancy losses. Among genetic risk factors, factor V Leiden and prothrombin gene mutations are responsible of spontaneous abortions, mainly late abortions. The rare antithrombin, protein C or protein S deficiencies are also implicated in some spontaneous abortions. Paternal genetic risk factors of thrombosis that could affect directly the foetus do not seem implicated in pregnancy losses. Antiphospholipid syndrome (APS) is the main acquired risk factor of spontaneous abortions, in 15% of cases. There are early abortions, by impaired throphoblast invasion by lupus anticoagulant or antiphospholipid, and late abortions by thrombosis in placental vessels. The treatment of APS in pregnant women, with aspirin and low molecular weight heparin, is save. An excessive generation of phospholipidic microparticles, low levels of annexin V on trophoblasts, the 4G/4G PAI-1 genotype could also explain some pregnancy losses.
