Thrombose hémostase et cancer : les mécanismes physiopathologiques en jeu

The pathogenesis of the prothrombotic state of cancer patients ismostly due to the ability of cancer cells to activate the coagulation system. There are several complex and not fully understood interactions between the malignant cell and the clotting system. Tumour cells possess the capacity to interact with the haemostatic system in multiple ways. The principal mechanisms include the expression of haemostatic proteins by tumour cells, the production of inflammatory cytokines and the direct adhesion of tumour cells to platelets, endothelial cells and monocytes. This paper summarizes the prothrombotic mechanisms of tumour cells and their role in both coagulation and tumour growth and metastasis.     

Two novel factor V null mutations associated with activated protein C resistance phenotype/genotype discrepancy

Activated protein C (APC) resistance phenotype/genotype discrepancy is a very rare event. The objective of this study was to characterize the molecular mechanisms in two cases of APC phenotype/genotype discrepancy. An approach using direct sequencing of each exon and splicing junctions of the factor V gene showed that two novel factor V null mutations combined with heterozygous factor V Leiden mutation were responsible for this discrepancy. Our results suggest the necessity to use both phenotypic and genotypic analyses in some cases to determine an accurate diagnosis.     

Evaluation of the care pathway in the context of the dispensing of emicizumab (Hemlibra) in community and hospital pharmacies in France: A patient satisfaction survey

Introduction

Since June 2021 in France, patients with haemophilia A with anti-factor VIII inhibitors and patients with severe haemophilia A without anti-factor VIII inhibitors, and treated with emicizumab (Hemlibra), have to choose the dispensing circuit community or hospital pharmacy.

Aim

To evaluate satisfaction of patients whether they choose dispensation from a community pharmacy or retained dispensation from the hospital pharmacy, to understand the main motivation for choosing the community or the hospital pharmacy.

Methods

All patients living in France, regardless of age, were eligible to participate. Between September 13, 2022, and January 9, 2023, 175 respondents answered the satisfaction survey, including 123 in community pharmacy and 52 in hospital pharmacy.

Results

Eighteen months after availability in community pharmacies, treatment accessibility is improved for the benefit of the patient. The door-to-door travel times are significantly reduced to the community pharmacy with an average gain of 16.5 min saved from the place of residence. Patients are mostly satisfied with the new dispensing circuit especially concerning the overall satisfaction (p < .0001), the travel time (p < .0001) and the strong relationship with the pharmacist (p = .0022) compared to hospital pharmacy.

Conclusion

Innovation in care pathways is showing its full potential in improving access to medication, made possible by the implementation of a rigorous organization accompanied by training to enable healthcare professionals involved in primary care to provide appropriate management.     

Standardisation of thrombin generation test - which reference plasma for TGT?: An international multicentre study

We have previously shown that standardisation and normalization of results improve the intercentre variability of the calibrated automated thrombin generation test (TGT). We suspected that the source of reference plasma (RP) might be a contributing factor to variability and compared 5 commercial RP and a RP provided by the NIBSC, in an international, multicentre study. The detailed composition of the 6 tested plasma samples was determined in the Haemostasis Labotatory in Lyon. The lot to lot consistency, intra-assay, inter-assay variability were calculated for all tested plasmas. The RP and 3 plasma samples (a normal control, a hypocoagulable and a hypercoagulable plasmas) were tested over 6 days, in 5 European centres. Results were normalised against each of the tested RP and intercentre variability of results was compared. All laboratories used the same reagents. Before normalization, the inter-centre variability was 19.8 to 27.3%. After normalization, we observed a significantly improved inter-laboratory variation with all tested RP, despite differences between them. These results clearly demonstrate that the inter-centre variability of TGT can be significantly reduced by using a reference plasma normalization, and that certain RP have a better capacity to reduce this variability than others.     

Haemophilia therapies

In the last few decades dramatic improvements in the management of haemophilia patients have occurred. Haemophilia has moved from a fatal or disabling disease to a hereditary disorder with available treatment and much better clinical outcomes. The safety of antihaemophilic factor concentrates has been dramatically improved and, in a multidisciplinary environment including haematologists, orthopaedic surgeons, paediatrics, infectiologists, specialised nurses and physiotherapists, complications related to haemophilia are now limited, markedly improving the quality of life of haemophiliacs. One can even think that the cure of haemophilia through gene therapy might occur in the next decades. Keeping this ultimate aim in mind, efforts at present are mainly focused on bioengineered Factor VIII/Factor IX concentrates with increased efficacy or longer half-life or decreased immunogenicity. In addition, several preclinical and clinical studies are being carried out for optimising and individually tailoring the therapeutic regimens of antihaemophilic therapies using global haemostasis tests in combination with the routine coagulation assays.     

A risk score for the management of pregnant women with increased risk of venous thromboembolism: a multicentre prospective study

Patients with thrombophilia and/or a history of venous thromboembolism (VTE) exhibit a high risk of thrombosis during pregnancy. The present multicentre study prospectively assessed a prophylaxis strategy, based on a risk score, in pregnancies with increased risk of VTE. Among 286 patients included in the study, 183 had a personal history of VTE (63·98%) and 191 patients (66·8%) had a thrombophilia marker. Eighty nine (46·6%) thrombophilic women had a personal history of VTE. Patients were assigned to one of three prophylaxis strategies according to the risk scoring system. In postpartum, all patients received low molecular weight heparin (LMWH) prophylaxis for at least 6 weeks. In antepartum, LMWH prophylaxis was prescribed to 61·8% of patients with high risk of VTE. Among them, 37·7% were treated in the third trimester only and 24·1% were treated throughout pregnancy. In this cohort, one antepartum-related VTE (0·35%) and two postpartum-related VTE (0·7%) occurred. No case of pulmonary embolism was observed during the study period. The rate of serious bleeding was 0·35%. There was no evidence of heparin-induced thrombocytopenia or osteoporosis. The use of a risk score may provide a rational decision process to implement safe and effective antepartum thromboprophylaxis in pregnant women at high risk of VTE.