Due to low bioavailability and high inter-individual variability, monitoring of dabigatran may be required in specific situations to prevent the risk of bleedings or thrombosis. The aim of the study was to determine which coagulation assay(s) could be used to assess the impact of dabig-atran on secondary haemostasis. Dabigatran was spiked at concentrations ranging from 4.7 ng/ml to 943.0 ng/ml in pooled citrated human platelet-poor plasma. The following clotting assays were performed: prothrombin time (PT); activated partial thromboplastin time (aPTT); thrombin time (TT); ecarin clotting time (ECT); ecarin chromo-genic assay (ECA); prothrombinase-induced clotting time (PiCT); activated clotting time (ACT); Hemoclot Thrombin Inhibitor (HTI) and thrombin generation assay (TGA). A concentration-dependent prolongation of PT, dPT, and aPTT was observed with aPTT being the more sensitive test. The results varied mostly due to the clotting reagent. HTI, ECT and TGA were the most sensitive tests but are not available 24 hours a day. In addition, HTI showed a linear correlation with a good reproduci-bility. Dabigatran induced a concentration-dependent delay and inhibition of tissue factor-induced TGA. Cut-offs related with higher risk of bleedings or thrombosis were defined for each reagent of aPTT and HTI. In conclusion, aPTT could be used for the monitoring of dabigatran and as screening test for the risk of overdose. However, because of its higher sensitivity, good reproducibility, excellent linear correlation at all doses, its simplicity of use, and possibilities of automation, HTI should be considered as the gold-standard.

/pdf/impact-of-dabigatran-on-a-large-panel-of-routine-or-specific-56m9buhbig.pdf

Impact of dabigatran on a large panel of routine or specific coagulation assays. Laboratory recommendations for monitoring of dabigatran etexilate.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/jth.12830

Multimodal assessment of non-specific hemostatic agents for apixaban reversal.

Low-molecular-weight heparin has been studied for the treatment of deep vein thrombosis in the inpatient setting and more recently in the outpatient setting. It is as safe and effective as unfractionated heparin and is effective when administered subcutaneously once or twice a day. Its bioavailability nears 100% and it has a longer half-life than unfractionated heparin, resulting in a prolonged anticoagulant effect. A reduction in thrombocytopenia and bleeding complications with low-molecular-weight heparin has been reported. Laboratory monitoring is unnecessary. Low-molecular-weight heparin provides the opportunity for home therapy.

Low-molecular-weight heparin for the treatment of deep vein thrombosis.

Inherited thrombophilia and cancer both independently increase the risk of venous thromboembolism (VTE). However, whether the increased VTE risk associated with inherited thrombophilia exists in cancer patients is less clear.Our objective was to determine the influence of inherited thrombophilia on VTE and bleeding risk in moderate-to-high-risk ambulatory cancer patients receiving chemotherapy.We conducted a post hoc analysis using blood samples from patients enrolled in the AVERT trial to determine if previously recognized thrombophilia gene mutations (prothrombin factor [F] II G20210A, FXI, fibrinogen gamma, serpin family A member 10, FV K858R, FXIII, FV Leiden [FVL], and ABO blood) were associated with VTE or bleeding during the 7-months after starting chemotherapy. Logistic regression was used to compare heterozygous and homozygous mutations (combined) to wild-type. VTE rates, bleeding rates, and risk differences for mutations stratified by prophylactic anticoagulation use were calculated.Of the 447 patients, there were 39 VTE and 39 bleeding events. The odds of VTE were significantly increased with FVL mutation and non-O blood type (odds ratio [OR]: 5.2; 95% CI: 1.9-14.7 and OR: 2.7; 95% CI: 1.2-6.1, respectively). The use of anticoagulation prophylaxis resulted in complete protection in FVL patients, whereas those not receiving anticoagulation had a VTE rate of 119 per 100 patient-years. Lower VTE rates were also observed in non-O blood type patients taking prophylactic anticoagulation. No other thrombophilia genes tested were significantly associated with VTE or bleeding.Our results indicate that FVL mutation and ABO blood type may be important VTE predictors in cancer patients starting chemotherapy. 

Thrombophilia Gene Mutations Predict Venous Thromboembolism in Ambulatory Cancer Patients Receiving Chemotherapy.

Les maladies cardiovasculaires représentent actuellement la première cause de morbidité et de mortalité en France. L’élargissement des indications du traitement par agents antiplaquettaires (AAP) dans ces affections conduit l’odontostomatologiste à soigner de plus en plus fréquemment des patients traités par AAP au long cours. Les patients sous AAP présentent des modifications de l’hémostase primaire qui interfèrent directement avec la réalisation de soins dentaires ou d’une intervention chirurgicale. Aussi, deux stratégies thérapeutiques s’opposent : l’arrêt du traitement par AAP, avec ou sans traitement substitutif, ou, au contraire, son maintien sans aucune modification. L’arrêt du traitement par AAP réduit le risque de saignement périopératoire. En revanche, cette attitude ne permet pas d’assurer une protection optimale vis-à-vis du risque thromboembolique. Inversement, la poursuite du traitement par AAP, si elle garantit la prévention du risque thromboembolique, majore théoriquement le risque de saignement per et postopératoire. L’objectif de ces recommandations est de définir une attitude cohérente et codifiée pour la prise en charge des patients traités sous AAP devant bénéficier de soins dentaires ou d’une intervention de chirurgie buccale, parodontale ou implantaire. Ces recommandations se limitent aux AAP prescrits au long cours, en ambulatoire. Elles concernent principalement l’aspirine et le clopiodogrel. Les AAP utilisés en cardiologie interventionnelle, notamment les anti-GP IIb/IIIa, en sont exclus. Les patients ayant une pathologie cardiovasculaire non stabilisée ou possédant d’autres anomalies constitutionnelles ou acquises de l’hémostase ne sont pas concernés par ces recommandations. Ces cas particuliers imposent une hospitalisation, une concertation pluridisciplinaire et une hémostase spécifique à chaque cas. La prise d’aspirine à fortes doses représente un cas particulier qui est abordé séparément. Ces recommandations s’adressent aux odontostomatologistes, aux médecins généralistes et aux médecins spécialistes (cardiologues, neurologues, anesthésistes réanimateurs...). Arrêt du traitement par AAP

Prise en charge des patients sous agents antiplaquettaires en odontostomatologie

Hémorragies et thromboses : du diagnostic au traitement

Resume L’objectif de ce travail est d’analyser la prise en charge des malades recevant un antagoniste de la vitamine K ou AVK ou des medicaments antiplaquettaires tels que l’aspirine et le clopidogrel et qui doivent subir un acte chirurgical ou invasif. Il etudie les modalites du relais de l’anticoagulation a l’aide d’une heparine de bas poids moleculaire (HBPM) ou d’une heparine non fractionnee (HNF). Les recommandations ou les suggestions utilisent le score de l’ACCP : les recommandations de grade 1 sont considerees comme fortes et indiquent que le benefice depasse ou ne depasse pas le risque, la charge et le cout du traitement. Les recommandations de grade 2 sont considerees comme des suggestions. Elles impliquent qu’a l’echelon individuel, le medecin pourra choisir differentes strategies. Les recommandations les plus importantes de ce travail sont les suivantes : • chez les porteurs d’une valve cardiaque mecanique ou ayant une fibrillation auriculaire ou une maladie veineuse thromboembolique (MVTE) a haut risque d’accident TE, il est recommande d’utiliser une HBPM par voie sous-cutanee a dose therapeutique durant l’interruption temporaire du traitement anticoagulant oral, plutot que l’absence de relais (grade 1C) ; • chez les memes patients, mais a risque modere d’accident TE, nous suggerons en relais de l’anticoagulation d’utiliser des doses therapeutiques sous-cutanees d’HBPM ou une dose intraveineuse d’HNF ou une faible dose d’HBPM sous-cutanee, plutot que l’absence de relais (grade 2C) ; • chez les memes patients pour lesquels le risque TE est faible, nous suggerons un relais par une HBPM sous-cutanee a faible dose ou l’absence de relais, plutot qu’un relais a dose therapeutique d’heparine (grade 2C) ; • chez les patients qui ont un stent coronaire nu et qui doivent subir un acte chirurgical moins de six semaines apres la mise en place du stent, nous recommandons de poursuivre l’aspirine et le clopidogrel dans la periode perioperatoire (grade 1C) ; • chez les patients qui ont eu un stent coronaire actif et qui necessitent un acte chirurgical dans les 12 mois qui suivent la mise en place du stent, il est recommande de poursuivre l’aspirine et le clopidogrel pendant la periode perioperatoire (grade 1C) ; • chez les patients qui doivent avoir une intervention dentaire mineure, nous recommandons de poursuivre les AVK en periode perioperatoire et d’utiliser un agent hemostatique actif par voie orale (grade 1B) ; • chez les patients devant subir un acte dermatologique mineur ou une operation de la cataracte, nous recommandons de poursuivre les AVK en periode perioperatoire (grade 1C).

La prise en charge périopératoire des traitements antithrombotiques. Des recommandations de l’American College of Chest Physicians (ACCP) à celles de la Haute Autorité de santé (HAS)

PO-73 Prevalence of cancer and congenital thrombophilia in 435 patients with acute venous thromboembolism (VTE)

The authors, via a long review of published studies, show that low-molecular weight heparin, with early start of antivitamin K, is actually the treatment of choice in thromboembolic disease.

[The treatment of deep venous thrombosis with low-molecular-weight heparin].

6 – Maladie Thromboembolique Veineuse

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