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Background: Acute pulmonary embolism (PE) is a life-threatening situation in cancer patients. In this situation, anticoagulant therapy is complex to administer due to the risk of bleeding. Only few studies have been conducted when these patients are admitted to the intensive care unit (ICU). The aim of this study was to assess the association between anticoagulation strategies as well as other factors with 90-day mortality in patients with cancer and PE admitted to ICU. Major bleeding was also evaluated according to the type of anticoagulation., Methods: Retrospective study carried out in 4 ICUs in France over a 12-year period (2009-2021). All patients with cancer and PE were included. An overlap propensity score weighting analysis was performed in the subgroup of patients treated with either unfractionated heparins (UFH) alone or low-molecular-weight heparins (LMWH) alone on 90-day mortality and major bleeding., Results: A total of 218 consecutive cancer patients admitted to ICU and presenting PE were included. The 90-day mortality rate was 42 % for the global cohort. After propensity score analysis in the subgroup of patients treated with either "UFH alone" (n = 80) or "LMWH alone" (n = 71), the 90-day mortality was similar in patients treated with UFH alone (42.6 %) vs LMWH alone (39.9 %): OR = 1.124, CI 95 % [0.571-2.214], p = 0.750. There was a significant increased toward major bleeding rates in the "UFH alone" group (25.5 %) as compared to "LMWH alone" group (11.5 %), p = 0.04., Conclusion: In 218 patients admitted to ICU and presenting PE, the 90-day mortality rate was 42 %. Treatment with UFH alone was associated with a mortality comparable to treatment with LMWH alone but it appeared to be more prone to major bleeding., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Background Patients with cancer have an elevated risk of venous thromboembolism. Importantly, patients with cancer, who have metastatic disease, renal insufficiency, or are receiving anticancer therapy, have an even higher risk of a recurrent event. Similarly, the risk of recurrent venous thromboembolism is higher than the risk of an initial event. To reduce the risk, extended duration of prophylaxis for up to six months with low-molecular-weight heparins such as dalteparin, enoxaparin, nadroparin, and tinzaparin is recommended by international guidelines. In this paper, the clinical and economic literature is reviewed to provide evidenced based recommendations based on clinical benefit and economic value. Methods A systematic review of major databases was conducted from January 1996 to October 2016 for randomized controlled trials evaluating the four distinct low-molecular-weight heparins against a vitamin K antagonists control group for the prevention of recurrent venous thromboembolism in patients with active cancer. This was then followed by the application of the National Institute of Health and Clinical Excellence guidance to assess the quality of all trials that met the inclusion criteria. Finally, the cost-effectiveness literature supporting the value proposition of each product was reviewed. Results Six randomized trials met the inclusion criteria. There were one, two, and three trials that compared dalteparin, tinzaparin, and enoxaparin to a vitamin K antagonists control group. However, there were no trials for nadroparin in the setting of secondary venous thromboembolism prevention. In addition, only the dalteparin and one of the tinzaparin trials were of high quality and adequately powered. Of the two studies, only the dalteparin trial reported a statistically significant benefit in terms of venous thromboembolism absolute risk reduction when compared to a vitamin K antagonists control group (HR = 0.48; p = 0.002). In addition, there was robust pharmacoeconomic data from Canada, the Netherlands, France, and Austria supporting the cost-effectiveness of dalteparin for this indication. There were no such studies for any of the other agents. Conclusions The totality of high-quality clinical and cost-effectiveness data supports the use of dalteparin over other low-molecular-weight heparins for preventing recurrent venous thromboembolism in patients with cancer. [ABSTRACT FROM AUTHOR]

The article presents abstracts of papers presented at the 39th European Society of Clinical Pharmacy (ESCP) European Symposium on Clinical Pharmacy and the 3th Société Française de Pharmacie Clinique (SFPC) Congress: Clinical Pharmacy at the Front Line of Innovations in Lyon, France, including "Hallucinations Due to Therapeutic Doses of Ertapenem," "Carboplatin Dosage in Overweight Patient: Case Report" and "Severe Hypokalemia Associated With Flucloxacillin."

Objectives: Compare costs associated with all-cause healthcare resource use (HCRU), stroke/systemic thromboembolism (STE) and major bleedings (MB) between patients with non-valvular atrial fibrillation (NVAF) initiating apixaban or other oral anticoagulants (OACs). Methods: We performed a retrospective cohort study using the French healthcare claims database, including NVAF patients between 2014/01/01 and 2016/12/31, followed until 2016/12/31. We used 4 sub-cohorts of OAC-naive patients, respectively initiating apixaban, dabigatran, rivaroxaban or VKAs. We matched patients initiating apixaban with patients initiating each other OACs using 1:n propensity score matching. All-cause HCRU and event-related costs by OAC treatment were estimated and compared between matched patients using generalised-linear models with gamma-distribution and two-part models. Results: There were 175,766 patients in the apixaban–VKA, 181,809 in the apixaban–rivaroxaban, and 42,490 in the apixaban–dabigatran matched cohorts. Patients initiating apixaban had significantly lower HCRU costs than patients initiating VKA (€1,105 vs. €1,578, p < 0.0001), dabigatran (€993 vs. €1,140, p < 0.0001) and rivaroxaban (€1,013 vs. €1,088 p < 0.0001). They have had significantly lower costs related to stroke/STE and MB than patients initiating VKA (respectively, €183 vs. €449 and €147 vs. €413; p < 0.0001), rivaroxaban (respectively, €145 vs. €197 and €129 vs. €193; p < 0.0001), and lower costs related to stroke/STE than patients initiating dabigatran (€135 vs. €192, p < 0.02). Costs related to MB were not significantly different in patients initiating apixaban and those initiating dabigatran (€119 vs. €149, p = 0.07). Conclusions: HCRU and most event-related costs were lower in patients initiating apixaban compared to other OACs. Apixaban may be cost-saving compared to VKAs, and significantly cheaper than other DOACs, although cost differences are limited. [ABSTRACT FROM AUTHOR]

This paper presents the result of a 4 year survey in France (1991-1994) based on the activity of a wildlife disease surveillance network (SAGIR). The purpose of this study was to evaluate the detrimental effects of anticoagulant (Ac) rodenticides in non-target wild animals. Ac poisoning accounted for a very limited number of the identified causes of death (1-3%) in most species. Predators (mainly foxes and buzzards) were potentially exposed to anticoagulant compounds (especially bromadiolone) via contaminated prey in some instances. The liver concentrations of bromadiolone residues were elevated and species-specific diagnostic values were determined. These values were quite similar to those reported in the literature when secondary anticoagulant poisoning was experimentally assessed.

Simple Summary: Venous thromboembolism (VTE) is a common and often fatal complication in cancer patients. The initial treatment for VTE in cancer patients is typically low molecular weight heparins (LMWH), a type of anticoagulant that prevents VTE from recurring. However, information on outcomes of LMWH treatment in cancer patients with VTE have not typically been collected from large national databases, such as the one in France. The aim of this study was to assess VTE recurrence, bleeding (a common side effect of anticoagulant treatment), and all-cause mortality in cancer patients in France who were prescribed LMWH for VTE in 2013–2018. Our results indicate that cancer patients who experience VTE have unmet medical needs due to high rates of mortality, VTE recurrence, and bleeding after LMWH treatment initiation. Our study may help further research on outcomes in cancer patients with VTE who receive the next generation of therapy, direct oral anticoagulants. Patients with cancer have an increased risk of developing venous thromboembolism (VTE) and an increased risk of death from VTE. Until recently, the standard of care for treatment of VTE in cancer patients was low molecular weight heparins (LMWH). To determine treatment patterns and outcomes, we performed an observational study using a nationwide health database. Treatment patterns, rates of bleeding, and VTE recurrence at 6 and 12 months were assessed in cancer patients with VTE in France prescribed LMWH in 2013–2018. Of 31,771 patients administered LMWH (mean age 66.3 years), 51.0% were male, 58.7% had pulmonary embolism, and 70.9% had metastatic disease. At 6 months LMWH persistence was 81.6%, VTE recurrence had occurred in 1256 patients (4.0%) at a crude rate per 100 person-months (PM) of 0.90, and bleeding had occurred in 1124 patients (3.5%) at a crude rate per 100 PM of 0.81. At 12 months, VTE recurrence had occurred in 1546 patients (4.9%) at a crude rate per 100 PM of 0.71 and bleeding had occurred in 1438 patients (4.5%) at a crude rate per 100 PM of 0.66. Overall, VTE-related clinical event rates were high among patients administered LMWH, suggesting an unmet medical need. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study is to assess international guidelines implementation concerning thromboprophylaxis strategy in myeloma patients treated with immunomodulatory drugs. Methods: This retrospective study includes multiple myeloma patients treated with immunomodulatory drugs between 2014 and 2017 in the Hematology department of a teaching hospital (Hospices Civils de Lyon, France) and followed by the multidisciplinary care plan for cancer outpatients ONCORAL (ONCological care for outpatients with ORAL anticancer drugs). Data from immunomodulatory drugs administration, thromboprophylaxis strategy and thrombotic events were collected from medical files. Adherence to 2010 International Myeloma Working Group (IMWG) guidelines was assessed. Results: 213 patients received at least one immunomodulatory drug: lenalidomide (60.9%), pomalidomide (24.0%) and thalidomide (15.1%). About two third of treatment lines (66.2%) were in accordance with IMWG recommendations. Among the others, 30.5% and 69.5% had thromboprophylaxis, respectively, superior or inferior to IMWG recommendations. 37 venous thrombotic events and 4 arterial thromboembolisms (one patient experienced both a stroke and deep venous thrombosis simultaneously) were reported. Conclusion: Thromboprophylaxis was systematically performed in myeloma patients treated with immunomodulatory drugs in this real-life retrospective cohort. However, the choice of anticoagulant or anti-platelet agent remains debatable, as adherence to existing guidelines was variable. [ABSTRACT FROM AUTHOR]

Background: Data directly comparing trends in the use of different oral anticoagulants (OACs) among patients with atrial fibrillation (AF) from different countries are limited. We addressed this using a large-scale network cohort study in the United States (US), Belgium, France, Germany, and the United Kingdom (UK).Methods: We used nine databases (claims or electronic health records) that had been converted into the Observational Medical Outcomes Partnership Common Data Model with analysis performed using open-source analytical tools. We identified adults with AF and a first OAC prescription, either vitamin K antagonist (VKA) or direct oral anticoagulant (DOAC), from 2010 to 2017. We described time trends in use, continuation, and switching.Results: In 2010, 87.5%-99.8% of patients started on a VKA. By 2017, the majority started on a DOAC: 87.0% (US), 88.3% (Belgium), 93.1% (France), 88.4% (Germany), and 86.1%-86.7% (UK). In the UK, DOACs became the most common starting OAC in 2015, 2-3 years later than elsewhere. Apixaban was the most common starting OAC by 2017, 50.2%-57.8% (US), 31.4% (Belgium), 45.9% (France), 39.5% (Germany), and 49.8%-50.5% (UK), followed by rivaroxaban, 24.8%-32.5% (US), 25.7% (Belgium), 38.4% (France), 24.9% (Germany), and 30.2%-31.2% (UK). Long-term treatment was less common in the US than in Europe, especially the UK. A minority of patients switched from their index OAC in the short and long term.Conclusions: From 2010 to 2017, VKA use had significantly declined and DOAC use had significantly increased in the US and Europe. Apixaban was the most prescribed OAC in 2017, followed by rivaroxaban. [ABSTRACT FROM AUTHOR]

Background: International guidelines recommend extended duration secondary prophylaxis in cancer patients who develop primary venous thromboembolism (VTE). Agent selection is guided in part by one large randomized trial (i.e., CLOT; Lee et al., N Engl J Med 349:146-53, 2003) which demonstrated that dalteparin reduced the relative risk of recurrence by 52% compared with oral vitamin K antagonists (VKA; HR = 0.48, 95% CI, 0.30 to 0.77). In a subgroup analysis from that same trial, patients with renal impairment also derived benefit with dalteparin (VTE rates = 3% vs. 17%; p = 0.011). To measure the economic value of secondary VTE prophylaxis with dalteparin, a patient-level pharmacoeconomic analysis was conducted from the Austrian and French healthcare system perspectives.Methods: Chapter 1 Healthcare resource use collected during the CLOT trial was extracted and converted into direct cost estimates. Incremental cost differences between the dalteparin and VKA groups were then combined with health state utilities to measure the cost per quality-adjusted life year (QALY) gained.Results: The dalteparin group had significantly higher costs than the VKA group in both countries (Austria: dalteparin = €2687 vs. VKA = €2012; France: dalteparin = €2053 vs. VKA = €1352: p < 0.001). However, when the incremental costs were combined with the utility gain, dalteparin had a cost of €6600 and €4900 per QALY gained in Austria and France, respectively. The analyses in patients with renal impairment suggested an even better economic profile, with the cost per QALY gained being less than €4000 in both countries.Conclusions: Secondary prophylaxis with dalteparin is a cost-effective alternative to VKA for the prevention of recurrent VTE in patients with cancer. [ABSTRACT FROM AUTHOR]

Aims: This prospective study was carried out to assess the feasibility and safety of venous figure-of-eight suture to achieve haemostasis after atrial fibrillation (AF) ablation.Methods and Results: Consecutive patients who underwent catheter ablation of AF were prospectively enrolled from February 2012 to September 2013. At the end of the procedure, a temporary subcutaneous 'Figure-of-eight' suture technique was used to achieve haemostasis. Anticoagulation strategy evolved during the study. Initially, vitamin K antagonists (VKAs) were stopped and replaced by administration of low-molecular-weight heparin. It was subsequently decided to perform these procedures without stopping VKA. With the arrival of direct oral anticoagulants (DOACs), it was decided to miss the evening dose before the procedure. One hundred and twenty-four patients were included. Seventy-three per cent of patients were male, and the mean age was 58 ± 10 years old. One hundred and twelve patients (90%) experienced paroxysmal AF and were treated by cryotherapy with the use of a 15 Fr outer diameter Flexcath Advance sheath. The 'Figure-of-eight' suture technique was able to be performed in all patients and was sufficient in 114 patients. Mechanical external compression was required for 10 patients. Three patients developed a haematoma. The overall incidence of haematoma was therefore 2.4%.Conclusion: Figure-of-eight suture is a fast closure technique that can be used as an efficient alternative to usual compression methods to prevent bleeding during high-intensity anticoagulation and the use of large-diameter venous sheaths and multiple femoral venous accesses. [ABSTRACT FROM AUTHOR]

Objectives To describe the characteristics of nursing home residents diagnosed with atrial fibrillation ( AF) and eligible for oral anticoagulants who did not receive these drugs and to detail the conditions that physicians who decide not to prescribe anticoagulants take into account. Design Cross-sectional. Setting Nursing home. Participants Nursing home residents with a history of AF (N = 1,085). Measurements Data were collected on clinical characteristics, geriatric syndromes, and antithrombotic regimen. Multivariate logistic regression was used to identify factors associated with nonprescription of anticoagulants. A standardized questionnaire was submitted to physicians in charge of patients with AF, to detail conditions associated with their medical decision not to prescribe anticoagulants. Results History of AF was present in 1,085 nursing home residents (10.1%), mean age 87, with a mean CHA2 DS2- VASc score of 5.1 ± 1.4. Of these residents with AF, 544 (50.1%) did not receive anticoagulants. Recurrent falls (odds ratio ( OR) = 4.9, 95% confidence interval ( CI) = 2.4-9.9, P < .001), past history of bleeding ( OR = 3.62, 95% CI = 1.54-8.51, P = .003), paroxysmal AF ( OR = 3.5, 95% CI = 1.83-6.66, P < .001), and advanced age ( OR = 1.1, 95% CI = 1.01-1.17, P = .02) were significantly associated with not prescribing anticoagulants. Recurrent falls (47%), cognitive impairment (22.6%), and advanced age (16.4%) were the main reasons for not prescribing anticoagulants. Conclusion The prevalence of AF in a cohort of very old nursing home residents was 10%. Anticoagulation was prescribed in fewer than 50% of eligible cases despite high individual risk of stroke. Geriatric syndromes, especially falls and cognitive disorders, were the main reported contraindications for prescribing anticoagulants. Physicians caring for those residents wrongly thought that paroxysmal AF caused fewer thromboembolic events than permanent AF, which explains lower rates of anticoagulant prescription in individuals with paroxysmal AF. [ABSTRACT FROM AUTHOR]

Objective: The objective of our study was to compare the standard protocol of anticoagulation to the Hepcon/HMS.Method: This study included forty-four patients who underwent coronary bypass grafting surgery (CABG), or biological aortic valve replacement (AVR). Unfractionated heparin (UH) was used for patients who underwent operations in the control group (n = 22) (300U/Kg of UH with a goal of an ACT of 400s). The heparin was antagonized dose/dose by protamine. For the patients who underwent operations in the HMS group (n = 22), the heparin and protamine doses were assessed by the Hepcon/HMS device.Results: The sex ratio amounted to 1.93 (29 men and 15 women) and the mean age was 70 ± 11 years. The patients in the HMS group had a chest closure time that was significantly shorter than patients in the control group. The times were, respectively, 42 ± 15 minutes and 68 ± 27 minutes (p = 0.001). The protamine/heparin ratio was significantly lower in the HMS group (0.62 ± 0.13 vs. 1 ± 0.11) (p = 0.0001). The postoperative bleeding amounted to 804 ± 729 ml in the HMS group versus 1416 ± 1103 in the control group (p = 0.016). In multivariate linear regression analysis, only two independent factors were significantly associated with bleeding: the Hepcon/HMS (OR = 0.1-p = 0.03) and the preoperative hemoglobin rate (OR = 1.4 - p = 0.05). Postoperatively, within 72 hours, the red blood cell transfusion was 1.04 ± 1.5 units for the HMS group and 2.1 ± 1.87 units for the control group (p = 0.05).Conclusion: During cardiac surgery under CPB, heparin and protamine titration with the Hepcon/HMS device could predict a lower protamine dose and lower postoperative bleeding without higher thromboembolic events, and lower perioperative red blood cell transfusion with a shorter chest closure time. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented which is concerned with an ancillary study which investigated heparin bridging therapy and bleeding events in octogenarian patients with atrial fibrillation.

Introduction. Anticoagulant rodenticides have been used for over 50 years to control rodent populations. Since their first introduction, resistance developed in rodents, and second-generation products, more active but also more toxic, have been marketed. These compounds are currently being reviewed under European Regulations. Methods. The purpose of this work is to describe anticoagulant poisoning based on retrospective data from French human and animal poison control centers. Cases from 2004 to 2007 were collected. Results. Overall, the proportion of anticoagulant exposure reported to the Lyon poison control center appeared very limited and mostly occurred in young children, with no or very limited clinical severity. Some cases also occurred after intentional use of anticoagulants in adults. Circumstances of exposure are predominantly accidental in man (77%). In animals, both domestic and wild species, anticoagulant exposure seems more common, and often more accompanied by clinical signs. Among domestic species, dogs represent over 60% of the cases: in wildlife hares and rabbits account for almost 50% of the submitted cases, followed by predators and scavengers. Conclusion. Rodenticides involved are representative of the market share of anticoagulants, for human and domestic animal exposures. In wildlife, bromadiolone and chlorophacinone are by far the most important products, being the only ones registered for field use. There is no report of mortality in the human data, and less than 1% of all exposure cases in domestic animals were fatal. [ABSTRACT FROM AUTHOR]

The article discusses a study on the distribution of Vitamin K epoxide reductace complex subunit1 (VKORC1) mutations in brown rats (Rattus norvegicus) in France to examine its resistance to anticoagulants. It says that the tail pieces of 200 rats were used for the study. It states that the blast software was used to detect homozygous mutations in the VKORC1 exons. The results revealed the association of Y139F mutation with the resistance of the rats to anticoagulants.