Prevention of perioperative venous thromboembolism: 2024 guidelines from the French Working Group on Perioperative Haemostasis (GIHP) developed in collaboration with the French Society of Anaesthesia and Intensive Care Medicine (SFAR), the French Society of Thrombosis and Haemostasis (SFTH) and the French Society of Vascular Medicine (SFMV) and endorsed by the French Society of Digestive Surgery (SFCD), the French Society of Pharmacology and Therapeutics (SFPT) and INNOVTE (Investigation Network On Venous ThromboEmbolism) network.

Background: Any surgical procedure carries a risk for venous thromboembolism (VTE), albeit variable. Improvements in medical and surgical practices and the shortening of care pathways due to the development of day surgery and enhanced recovery after surgery, have reduced the perioperative risk for VTE.

Objective: A collaborative working group of experts in perioperative haemostasis updated in 2024 the recommendations for the Prevention of perioperative venous thromboembolism published in 2011.

Latest advances in the reversal strategies for direct oral anticoagulants.

Background: Since the late 2000s, Europe has granted approval for various thrombotic risk-related uses of direct oral anticoagulants (DOACs). Unlike traditional anticoagulants, DOACs do not necessitate routine coagulation monitoring. Nevertheless, clinical practice often encounters bleeding events associated with these medications, making the need for effective reversal strategies evident.

Dose-response relationships of intravenous and perineural dexamethasone as adjuvants to peripheral nerve blocks: a systematic review and model-based network meta-analysis.

Background: Superiority of perineural over intravenous dexamethasone at extending nerve block analgesia has been suggested but without considering the dose-response relationships for each route of administration.

Methods: Randomised control studies that evaluated intravenous or perineural dexamethasone as an adjuvant to unilateral peripheral nerve blocks in adults were searched up to October 2023 in MEDLINE, Central, Google Scholar, and reference lists of previous systematic reviews. The Cochrane Risk-of-Bias tool was used.

A framework to characterise the reproducibility of meta-analysis results with its application to direct oral anticoagulants in the acute treatment of venous thromboembolism.

The number of meta-analyses of aggregate data has dramatically increased due to the facility of obtaining data from publications and the development of free, easy-to-use, and specialised statistical software. Even when meta-analyses include the same studies, their results may vary owing to different methodological choices. Assessment of the replication of meta-analysis provides an example of the variation of effect 'naturally' observed between multiple research projects.

Replication of systematic reviews: is it to the benefit or detriment of methodological quality?

Objectives: To perform an overview of the overlap of systematic reviews (SRs) assessing direct oral anticoagulants and characterize these reviews in terms of bias and methodological quality (PROSPERO: CRD42022316273).

Study Design And Setting: A PubMed-indexed search was performed from inception to January 31, 2022 to identify SRs evaluating direct oral anticoagulants in patients treated for an acute venous thromboembolism. The risk of bias of these SRs was assessed according to the Risk Of Bias In Systematic reviews tool.

Fetal Movement Counting in Prolonged Pregnancies: The COMPTAMAF Prospective Randomized Trial.

In prolonged pregnancies, the risks of neonatal morbidity and mortality are increased. The aim of this trial was to assess the benefits of maternal information about fetal movement (FM) counting on neonatal outcomes in prolonged pregnancy. It was a prospective, single center, randomized, open-label study conducted from October 2019 to March 2022.

Adjusted versus fixed doses of LMWHs in trauma patients: A systematic review and meta-analysis.

Purpose: Venous thromboembolism (VTE) causes significant morbidity and mortality in patients with traumatic injuries, despite thromboprophylaxis. To decrease both thrombotic and bleeding risks, some authors suggest adjusting the thromboprophylactic doses of low-molecular-weight heparins (LMWH), in particular according to body weight at treatment initiation or to changes in anti-factor Xa level during treatment. Our objective was to estimate in trauma patients the efficacy and safety of such adjustments, compared with the conventional strategy of fixed-dose LMWH thromboprophylaxis.

Robust K-PD model for activated clotting time prediction and UFH dose individualisation during cardiopulmonary bypass.

Background And Objective: Activated clotting time (ACT) is a point-of-care test used to monitor the effect of unfractionated heparin (UFH) during cardiopulmonary bypass (CPB). This test sometimes returns aberrant values, which can lead to the administration of an inappropriate dosing regimen. The development of a population-robust K-PD model of UFH could allow the individualisation and automation of UFH therapy during CPB.

Pharmacokinetics of enoxaparin in COVID-19 critically ill patients.

Background: In intensive-care unit (ICU) patients, pathophysiological changes may affect the pharmacokinetics of enoxaparin and result in underdosing.

Objectives: To develop a pharmacokinetic model of enoxaparin to predict the time-exposure profiles of various thromboprophylactic regimens in COVID-19 ICU-patients.

Methods: This was a retrospective study in ICUs of two French hospitals.

Exposure-Response Relationship of Tranexamic Acid in Cardiac Surgery.

Background: It is unclear whether high-dose regimens of tranexamic acid in cardiac surgery (total dose, 80 to 100 mg/kg) confer a clinical advantage over low-dose regimens (total dose, approximately 20 mg/kg), particularly as tranexamic acid-associated seizure may be dose-related. The authors' aim was to characterize the exposure-response relationship of this drug.

Methods: Databases were searched for randomized controlled trials of intravenous tranexamic acid in adult patients undergoing cardiopulmonary bypass surgery.

Predicting the dose of vancomycin in ICU patients receiving different types of RRT therapy: a model-based meta-analytic approach.

Aim: Previous pharmacokinetic (PK) studies have proposed various dosing regimens for vancomycin in intensive care unit (ICU) patients undergoing renal replacement therapy (RRT), but all are restricted to specific RRT modalities. To be useful in practice, a population PK model would need to predict vancomycin clearance during any RRT modality. Development of such a model is feasible using meta-analysis of published summarized estimates of vancomycin PK parameters.

Is tranexamic acid exposure related to blood loss in hip arthroplasty? A pharmacokinetic-pharmacodynamic study.

Aims: Tranexamic acid (TXA) is an antifibrinolytic agent, decreasing blood loss in hip arthroplasty. The present study investigated the relationship between TXA exposure markers, including the time above the in vitro threshold reported for inhibition of fibrinolysis (10 mg l ), and perioperative blood loss.

Methods: Data were obtained from a prospective, double-blind, parallel-arm, randomized superiority study in hip arthroplasty.

Intravenous Tranexamic Acid Bolus plus Infusion Is Not More Effective than a Single Bolus in Primary Hip Arthroplasty: A Randomized Controlled Trial.

Background: Preoperative administration of the antifibrinolytic agent tranexamic acid reduces bleeding in patients undergoing hip arthroplasty. Increased fibrinolytic activity is maintained throughout the first day postoperation. The objective of the study was to determine whether additional perioperative administration of tranexamic acid would further reduce blood loss.

Quantification of total and unbound tranexamic acid in human plasma by ultrafiltration liquid chromatography/tandem mass spectrometry: application to pharmacokinetic analysis.

The present work describes the development and validation of rapid, sensitive and accurate liquid chromatography method, coupled with tandem mass spectrometry detection, for quantification of tranexamic acid in human plasma using isotopically labeled internal standard (IS). A one-step plasma protein precipitation was performed with acetonitrile. UPLC BEH amide column was used for chromatographic separation.

PK evaluation of fondaparinux sodium for the treatment of thrombosis.

Introduction: Fondaparinux sodium (pentasaccharide) was the first of a new class of antithrombotic agents developed for the prevention and treatment of venous thromboembolism (VTE), blocking thrombin generation by selectively inhibiting factor Xa.

Areas Covered: This review focuses on the currently available information evaluating the pharmacokinetics, pharmacodynamics, clinical efficacy and safety of fondaparinux in the prevention and treatment of VTE and treatment of acute coronary syndromes (ACS).

Expert Opinion: Fondaparinux is an alternative to low-molecular-weight heparins (LMWH) for thromboprophylaxis in various clinical settings (major orthopedic surgery of the lower limbs, major abdominal surgery, immobilized medical patients at high risk of VTE), as well as for the treatment of VTE (deep venous thrombosis, pulmonary embolism).

Cervical epidural anesthesia is associated with increased cancer-free survival in laryngeal and hypopharyngeal cancer surgery: a retrospective propensity-matched analysis.

Background And Objectives: Regional anesthesia preserves perioperative immune competence and may reduce the risk of recurrence and metastasis after cancer surgery. Cervical epidural anesthesia provides adequate analgesia for head and neck cancer surgery, but its impact on cancer recurrence is unknown.

Methods: This study was a single-center retrospective cohort study of patients undergoing larynx or hypopharynx cancer surgery between January 1984 and December 2008.

A semi-mechanistic absorption model to evaluate drug-drug interaction with dabigatran: application with clarithromycin.

Aim: The aim of this study was to develop a PK/PD model to assess drug-drug interactions between dabigatran and P-gp modulators, using the example of clarithromycin, a strong inhibitor of P-gp.

Methods: Ten healthy male volunteers were randomized to receive in the first treatment period a single 300 mg dose of dabigatran etexilate (DE) and in the second treatment period 500 mg clarithromycin twice daily during 3 days and then 300 mg DE plus 500 mg clarithromycin on the fourth day, or the same treatments in the reverse sequence. Dabigatran plasma concentration and ecarin clotting time (ECT) were measured on 11 blood samples.

Dabigatran: rational dose individualisation and monitoring guidance is needed.

Dabigatran is the first oral anticoagulant to be introduced in New Zealand without prescribing restrictions for over 50 years. Not surprisingly, the drug has created a great deal of interest amongst health care providers as well as the general public and media. There seems to be a general feeling that warfarin, with its requisite dose adjustments and INR monitoring, is an outdated drug and should be shelved in favour of this novel agent.

Pharmacokinetics of fondaparinux 1.5 mg once daily in a real-world cohort of patients with renal impairment undergoing major orthopaedic surgery.

Purpose: Fondaparinux, a selective activator factor X (factor Xa) inhibitor, is effective and safe for preventing venous thromboembolism after major orthopaedic surgery (MOS) at the once-daily subcutaneous dose of 2.5 mg. As the drug is mainly eliminated by the kidneys, a reduced dosage (1.

Population pharmacokinetics of fondaparinux administered at prophylactic doses after major orthopaedic surgery in everyday practice.

Fondaparinux is a synthetic antithrombotic agent with specific anti-factor Xa activity. A population pharmacokinetic model of fondaparinux, based on data obtained in patients included in phase II/III trials, has been described. However, the validity of this model in everyday practice needed to be confirmed.

Ultra-performance LC MS/MS method for quantification of clopidogrel active metabolite.

A sensible ultra-performance LC-MS method was developed and validated for the quantification of clopidogrel active metabolite in human plasma, with clopidogrel D4 as internal standard. Plasma pretreatment involved a one-step protein precipitation with acetonitrile. The separation was performed by reverse-phase chromatography on a C8 column.

[Budget impact analysis of Pradaxa thromboprophylaxis after total hip or total knee replacement].

Venous thromboembolism is a serious disease that can be life-threatening in case of pulmonary embolism or induce major sequelae. Patients undergoing major orthopaedic surgery represent a population at high risk of venous thromboembolism. Recently Pradaxa has demonstrated its efficacy and safety versus enoxaparin in 2 pivotal trials.